Q2 2022 Gritstone bio Inc Earnings Call
Welcome to increase store bio second quarter 2022 conference call.
Please note this event is being recorded.
It is now my pleasure to introduce Josh make they'll go direct of Investor Relations and corporate communications at Greif Stone.
Go ahead Sir.
Thank you operator, and thank you everyone for joining us for Great Stones conference call to discuss our financial results clinical and business update for the second quarter of 2022 with.
With me on the call today from Griggstown are indirectly co founder President and CEO , Celia economies Executive Vice President and Chief Financial Officer, and joining us for the Q&A portion will be care and use our head of R&D.
Today after the market closed we issued a press release, providing our second quarter 2022 financial results clinical and business update.
The press release is available on our website.
To remind you that today's call is being webcast live via a link on gravestones Investor Relations Web site, where a replay will also be available after its completion.
After our prepared remarks, we will open up the call for Q&A. During the course of this call. We will make forward looking statements based on current expectations.
Forward looking statements are subject to a number of significant risks and uncertainties and our actual results may differ materially from those described we encourage you to review the risk factors in our most recent forms 10-Q filed with the US Securities and Exchange Commission and available on our website.
All statements on this call are native ads today based on information currently available to us except as required by law, we disclaim any obligation to update such statements. Even if our views change with that let me turn the call over to Andrew Andrew.
Thank you George and good afternoon, everybody. Thanks for joining us for our second quarter 2022 conference calls and what is grid Stone's first earnings call.
We decided to hold the coal this quarter because we believe it's helpful to speak to our updates in a little more detailed than can be provided in today's press release and also to provide you an opportunity to answer to ask and for us to answer questions.
We hope you will find it useful and we intend to hold tools for future earnings on an as needed basis.
This is an exciting time for great strength significant momentum is building for our clinical stage oncology programs. Greenwich is now in two randomized trials in earlier stage colorectal cancer and slate is progressing nicely in phase III for the treatment of advanced solid tumors.
And for our infectious disease programs, we are making great strides in realizing the incredible potential of our T cell enhanced self amplifying mrna vaccines for viral diseases.
Naturally we have sufficient runway to see all of our 2022 2023 clinical catalysts through and see here, we'll walk through all of the details on our financials towards the end of this call.
First and foremost I'm excited for the data that we expect to deliver in the coming months, which we believe will further validate our platforms and overall approach in both infectious disease and cancer.
We know a year and we expect several data sets from coal the second generation T cell enhanced COVID-19 vaccine program, using our self amplifying mrna or Sam RNA technology platform.
We are well aware of the need for a vaccine that generates broad and durable responses to both the current and future variance themselves could be too and we saw much discussion. These goals last week's Whitehouse summit.
Neutralizing antibodies elicited by first generation vaccines to cells could it be two variance.
Pits have quite short half lives and.
Measurements of antibody duration because assumes greater importance.
We have good stone our leaders in the Sam RNA field, having been the first to study this novel vector klos in clinical trials and the likely extended duration of antigen expression associated with Sam RNA may positively impact antibody duration.
We are optimistic that our Sem RNA vaccine approach to sales could be to and other pathogens could provide significant meaningful clinical differentiation.
Now in January of this year, we shared data from the first cohort of our phase one coal boost study showing that our Sam RNA vaccine candidate was effective of generating strong immune responses when used as a boost following two doses.
That said, we have all the astrazeneca vaccine.
Specifically, our vaccine candidate demonstrated peak neutralizing antibody titers comparable to the best in class mrna vaccine modality spikes. Thanks.
And we observed reduction of de Novo T cell responses to conserved regions of non spike genes included in the vaccine construct.
And this was when our Sam RNA vaccine candidate was administered at just 10 micrograms 110th of the dose of the Mcdonough vaccine.
What im excited to share with you today is a follow up data from the first two cohorts of subjects.
<unk> with just a single dose of either 10 or 30 micrograms of the Sam RNA vaccine candidate demonstrated that the robust neutralizing antibody response seen in January persisted without decay for at least six months.
You can see a slide on these data and our corporate presentation available on the Investor Relations section of our website.
Now this is a small subset of 70 subjects, but nonetheless, an early and highly encouraging signal that Sam RNA can generate more durable immune response and first generation products.
It is a small number of subjects since the study the long term response to single booster vaccination, we had to exclude those many subjects that chose to receive more than one boost over the six month period.
The breadth of the neutralizing antibody response, let's take elicited by Osama RNA boost is also encouraging.
While neutralization of Wild type Spike is the highest as expected of course since that is the variant delivered within the vaccine the.
The drop off of neutralizing potency against key variants such as Omicron is only around 10 fold versus the 40 volt typically seen with first generation products.
The Reactogenic D of the vaccine candidate is as expected for potent vaccines and remains consistent with data we presented in January of this year.
A degree of reacted unity of the 30 microgram dose level is slightly greater than that to 10 micrograms, although tolerable and we have selected 10 micrograms is they'll go forward dose.
It is important to recognize that self amplifying mrna is fundamentally different from the first generation mrna vaccines.
Continued rounds of RNA replication deliver different immune response kinetics and long term antigen persistence may be driving the potentially superior <unk> immune response that we are observing in these early data.
We will be presenting additional results from third the cohorts from the KOL boost study.
<unk> 2022 in October and we plan to share preliminary data from coal setting as well.
We've dosed over 100 subjects in the coal <unk> study in South Africa, and these are all vaccine naive subjects. So those data are very important to the characterization of this compelling platform.
The recent publication of our nonhuman Primate Challenge study data in nature Communications provides nice third party recognition for this program.
Let's turn to cancer.
In September of this year, we will share data from slate are off the shelf <unk> vaccine program.
Any oral presentation during the European Society of medical oncology or ESMO annual meeting.
Recall that results from version one of slate. We're encouraging you can review these in a previous press releases.
Early Immunogenicity data from this phase II trial with the second generation product candidate focused exclusively on K, Ross and termed slate K raws were presented at ACR in April .
Suggesting that slate K, Ras, what's driving stronger CDA T cell responses to mutant K Ras than the first version of version one.
Many oral presentation at ESMO, we intend to share initial clinical efficacy and safety data from the ongoing phase II single arm study of <unk> in patients with advanced non small cell lung cancer and colorectal cancer.
<unk> is an exciting immunotherapy candidate in part because it includes not only the thing is <unk> mutation, but several other K Ras mutations all in a single immunotherapy product candidate, which gives it the potential to address the substantial patient population across multiple tumor types.
Observing molecular and clinical responses in end stage patients would capitalize a strong desire to launch clinical trials in earlier disease settings, where immunotherapy has more time to drive an immune response and consequently impact disease.
Of note. The initial results we plan to share. It is no could provide proof of concepts beyond just targeting <unk>. There are many other new engine targets that are shared between cancer patients that could be the basis of novel product candidates in other words, where mutant <unk> leads others may follow.
Granite is our individualized <unk> vaccine program for solid tumors and it is rapidly advancing in the clinic.
This year, we've taken the program into a randomized potentially registrational phase III trial in newly diagnosed metastatic colorectal cancer or CRC patients.
The phase three is underway and we're looking forward to sharing initial phase two data in the second half of next year.
We also have a randomized controlled phase II trial that is open for enrollment for patients with high risk stage, three colon cancer, who are circulating tumor DNA positive or Cte DNA positive. After the definitive surgery. This of course has a population of very high risk of recurrence.
The follow up data from our phase one two study in granite.
<unk> has demonstrated the correlation between molecular response as measured by a reduction in Cte DNA and extended overall survival. These are very encouraging data there.
Use of Cte DNA as a short term efficacy biomarker for novel Immunotherapies is becoming more widely accepted for two good reasons.
Firstly traditional radiology is tailing is it reliable true for assessments of immunotherapy benefit.
And secondly, Cte DNA response appears to be performing as it reliable surrogates for overall survival in multiple settings.
The FDA has taken notice and issued draft guidance, a few months ago regarding the potential role of Cte DNA in drug development and early stage solid cancers.
And two weeks ago, the friends of cancer research held a public meeting, including high level members of the FDA on potential role for <unk> analysis in drug development in more advanced disease highly pertinent to our granite program.
Tony back to our day, two with Cte DNA. The median overall survival of CLC patients who demonstrated molecular response within our branded phase. One two study has not been reached and this loss reported in May is 18 months and growing.
This compares to seven eight months median overall survival in patients who did not have molecular response.
Which is in line with the six to seven months median overall survival typically seen with multiple therapies in the third line colorectal cancer setting.
Additionally, some of our patients had protein biomarkers, such as CA, and CA 19, nine which tracks with the disease burden and changes in these biomarkers were highly correlated with what was observed in Cte DNA.
This consistency within the small data set provides encouraging validation program that program.
Importantly, no new safety concerns have arisen.
The patients enrolled in this phase one two trial had been treated with two prior therapies and have a low probability of survival beyond the year.
What we are observing even in these very advanced CRC patients is the granite has the potential to profoundly change the disease kinetics and approximately half of patients.
As we move into an early disease context, with healthier patients better immune systems and more time premium responses to Mount and take effect. It is likely that the frequency and magnitude of granite benefit will increase.
This is a truly exciting prospect for a large population of patients for whom the immunotherapy has not yet delivered any benefit.
Beyond granted colon slate, we continue to apply a broad set of capabilities in oncology and infectious diseases through some promising preclinical work and strategic partnerships.
Our partnership with Gilead for the development of a therapeutic vaccine for HIV remains in place an active.
The IND for this program was cleared in the fourth quarter of 2021 and.
And you May recall, the Gilead has an option to advanced beyond the phase one study in this program, which would trigger a $40 million milestone payment to grit stone.
Ongoing preclinical projects include a pan Corona virus program, where we're deploying our deploying our RNA platform to deliver multiple spike elements plus broadly conserve T cell epitopes from family members beyond yourselves could be two to drive potentially broad clinical corona virus immunity.
We also have a program aiming to develop an optimal immunogen Inc.
The context of human Papilloma virus, which is being funded by the Gates Foundation.
We continue looking at other infectious disease pathogens, the future therapeutic and prophylactic programs.
The suite of capabilities, we've developed an infectious diseases from T cell antigen identification within viral genomes to the clinical application of our potential best in class form of mrna vaccine vector to robust assessments of T cell responses and clinical trials are all highly desirable.
Our partnerships with Gilead NIAD, the Bill and Melinda Gates Foundation, and Seppi underscore this and these capabilities are likely to be of interest to other potential partners.
Regarding our financial status and the state of the capital markets I'm confident in how we as a company and navigating these turbulent times, we are being prudent prioritizing programs and implementing continuous capital conservation measures were also being proactive the credit facility. The Seo team have established provides us an option to tap non dilutive.
Should we choose <unk>.
Bridgestone has been through cycles with capital markets before and I am confident in our ability to navigate this one.
As I stated this is an exciting time for <unk>, we have a very attractive clinical stage and <unk> platform.
Attention is best in class <unk> mrna vaccine that has broad potential applicability in multiple potential value creation milestones in the near future.
I'll now turn the call over to <unk>, who will discuss our financial results for the second quarter CVR.
Thank you Andrew Good afternoon, everyone quite soon and then the second quarter with $159 2 million in cash cash equivalents marketable securities and restricted cash as Andrew already mentioned, we have taken several measures to fortify our cash position.
And our runway in recent months.
These include but are not limited to discontinuation of the call immuno compromised study pack.
Passive immunization has now address it more for now.
Only been hiring at a critical new positions and backfill and while reducing our general and administrative costs where possible.
Additionally, we established a credit term facility with Hercules capital and Silicon Valley Bank for up to $80 million subsequent to the quarters end and then with your $20 million $30 million, that's available that closing our <unk>.
Conservation measures alone extend our runway by a quarter.
Q4 of 2023.
Facility provides us further flexibility.
With respect to the details of the credit facility, an additional $10 million is available at our request.
<unk> 2023.
$50 million remains available in tranches upon achievement of certain milestones on June 15th 2024.
We are under no obligation to draw funds in the future and there are no warrants associated with this transaction.
Auction.
Turning to our Q2 2022 operating result.
Recorded in research and development expenses of $27 3 million credit quarter that ended June 32022.
Compared with $22 1 million.
Same period last year.
The increase in R&D costs are mainly related to the launch of our new granite studies.
<unk> in first line colorectal cancer, and a phase III adjuvant therapy for colon cancer, along with our call programs. Both the core business and cross shopping centers that were initiated at the end of 2021 and the beginning of 2020 and scale.
We also recorded that general and administrative expenses were $7 8 million during the second quarter of 2020, compared with $5 9 million.
Sure.
The increase was primarily attributable to increases in personnel related expenses and professional service is growing at cost.
Net loss was $29 5 million for the second quarter of 2012, compared with $25 1 million for the same period last year.
Finally as of June 32022, quite sound had approximately 73.006 million 89 shares of common stock outstanding and pre funded warrants outstanding purchased $13 million 573, 704 shares of common stock at a nominal exercise.
<unk> per share as of June 32000, 2010.
I'll now turn the call back over to Andrew for some closing remarks Andrew.
Thank you Sir.
As we look ahead to the remainder of this year I can speak on behalf of the entire grid <unk> to say that we're more excited than ever about the potential of our innovative cancer and infectious disease platforms and very much looking forward to the critical data outputs that will be flowing over the next few months and throughout 2023.
And at this time I would like to thank you all for joining us today and I'll turn the call over to the operator for questions operator.
Thank you, ladies and gentlemen, if you would like to ask a question. Please take note by pressing star one on your touch two important if youre using a speakerphone. Please make sure. Your mute function is turned off Tau Youll statement reached our agreement again press star one to ask the question a pause just for a moment assemble the queue.
We take our first question from Marc Frahm with Cowen. Your line is open. Please go ahead.
Thanks for taking the questions and congrats on the data.
For Andrew and I guess Karan.
Just given the data you showed today in Canada.
The potential durability benefits that youre seeing on titers I.
I guess can you confirm that these patients arent seeing any evidence that they've been infected or what gives you confidence.
Evidence that theyre not getting exposed to immigrants I believe the data youre comparing to the samples were actually taken when maybe overcrowding in particular.
It was not circulation.
Yes.
Yes, thanks for the question Mark.
Karen you saw head of R&D is joining us for Q&A. So I'll ask <unk> to answer that question Karen.
Yes. Thank you very much of course.
<unk>.
Our focus to make sure that post.
Amplifying RNA vaccination.
Individuals did not getting infected with omicron so.
Nuclear perhaps it so rolliche he had actually two individuals who didnt get infected with a nucleocapsid Robert G increase significantly they are not part of our data sets.
We remove them and so the subject that we are showing in our data perhaps they have not been in fact that very good question. Thank you.
Okay.
Very helpful. Thanks, and then a similar idea.
When we look towards the <unk> data.
<unk> naive.
Patient later.
How should we interpret that data and kind of what.
Whats the good response, there given again these patients while.
While they may not have received vaccine in South Africa, they likely have had at least one if not multiple COVID-19 exposures.
Yes.
Excellent question, so basically again at baseline.
Scott a pre vaccination baseline sample or we look for it spikes serology look fun tapscott serology.
Anyone expected previously.
Let's call that it's positive and therefore, even in the naive cohort, we will see who have had previous exposure to call that.
Obviously very important for us to assess and we will have to debate that to really understand with naive and who had previous exposure.
Alright, Thank you kind of just for clarity.
We actually treat two cohorts.
South Africa at each dose level.
And the subjects are divided into quote convalescent and naive as Karen stated the allocated to each of those cohorts based upon that baseline anti nuclear protein serology.
And so we separate them out consciously mindful of exactly what you just said and those who are.
And antibody positive at baseline receive a single dose of vaccine convalescent group, whereas those who are antibody negative nave group are given two doses of the vaccine.
Okay, Great. That's very helpful. And then maybe just following up on all of them.
Whats the next steps might be.
And kind of.
What appetite you see out there among.
Maybe non commercial entities too.
To help fund novel vaccines that rather than just continuing to iterate.
On the approved vaccines.
Sure.
Yes, I think the.
Recognition that the first generation products was clearly extreme.
Extremely effective at limiting the impacts of the pandemic.
Do have some constraints and limitations.
Clearly variance proofing is one limitation and compounding that is lack of antibody persistence.
And so if you receive spike vaccine that is Wuhan spike, let's say all of those circled ancestral variant.
And then you will Mount a good antibody response to the first generation product.
The potency against some of the variance is significantly lower as we know with Omicron. For example, that's often about 40 fold lower.
Potency. So thats problem number one is that the variance is not anticipated very effectively and number two is that over time. Those titles, then teekay and fairly quickly fall below the protective threshold.
So you have this double whammy effect that the variant proofing is limited and the Teekay is relatively swift.
So with antibodies, obviously, what we may be seeing with our Sam RNA product is that the teekay.
Concern is mitigated and therefore, if I'm able to generate good titers of neutralizing antibodies at baseline.
Obviously that potentially will help sustain clear.
Clinical protection against the variants that are covered by those antibodies. Then of course, we have the T cell side of the house, which is separate.
The more we demonstrate differentiation the more interested people will be in this program.
And so I think there's a convergence now of growing interest amongst the parties.
The notion of superior vaccines that address the emerging limitations of the first generation products.
And our ability to demonstrate meaningful differentiation along those key axes and obviously, it's the combination of those two elements that potentially will drive us towards a pivotal trial, we're obviously not quite there yet, but thats potentially where we are heading.
Alright, thank you.
Thanks Mark.
Thank you we'll take our next question from Kevin Portland would be <unk>. Your line is open.
Hi, Thanks for taking the questions. It's Tom I'll go there.
I had a few questions about the remarkable Sam effect.
How much do you understand it as it is the RNA is still around are you, adding T cell epitopes or is it just Sam RNA when you get it right you get inherently more T cell response, but I guess the bigger question is are you generating IP around this approach.
The second question, Yes, we're obviously pie and is in the self amplifying mrna field. We were the first to put this construct into humans and of course that helps from an intellectual property perspective.
<unk> recognized that as ever with complex biologics manufacturing is really important and we are manufacturing our own products and it's not just patents, but also know how and trade secrets that can provide real benefit.
So that's the answer the second part of your question in regard to the fascinating first part of your question I'll pick it up on over to Karen.
Yes. Thank you very much so what do we know about self amplifying RNA, we did pro forma bio distribution studies, so our could leak. Some mrna they have published data is suggesting.
The half life of around 20% to 24 hours when needed a bite distributions steady BCE self amplifying RNA.
In the muscle cells for a couple of weeks. So the duration of aimed at CIT and presented to the immune system is significantly longer at the same time the replication.
The application phase self amplifying RNA intermediate forms of R&D being generated which we know triggers.
Ian responses, which we believe is also helping to make sure that that could lead to.
T cell activation, so I think it's a combination.
Our ability of antigen expression.
As well as presenting the antigen to the T cell.
Ex Vienna.
The interest.
Leading to the east.
T cell to the T cell activation and also a durability of stadium respondents.
Okay. Thank you and if I can ask a quick question on the first line CRC trial.
You are probably very interested in the Cte DNA responses, but from a regulatory point of view is this really a pure OS trial is there anything you would see before OS that would matter.
Yes, it's a good question Tom.
The primary endpoint for the phase III is Cte DNA response, now obviously that is not currently recognized as a registrational endpoint. Although there is a lot of activity in the space and as we've discussed previously I think there are two reasons for that number one radiology and standard <unk>.
<unk> has clear limitations with immunotherapy.
I think it both Mrs. Some.
Benefit and also misclassified as people as progression when it is not true progression. It is the so called pseudo progression.
And this may be more of an issue in something like colorectal cancer, where the lesions are pretty cold a baseline and if we're successful with our product we generate T cells that recognize tumor neo antigens.
T cells infiltrate tumors demonstrated this and then they proliferate that's the intention so at some level you actually want to see expansion of the lesion as a market that youll T cells are doing what theyre intended to do and of course. They should then start killing tumor cells and this is the challenge we don't know that relative.
Balance of how many bad guys tumor cells that are being killed and how many good guys T cells proliferating because it's the sum of those two populations that is measured by radiology, which is a very crude tool that simply can't tell them apart.
This is the challenge with re system, we're seeing lots of examples now where research is leaving us a little bit in the lurch.
By Misclassified patients and even just missing benefit immuno call being probably the best known example, <unk>.
<unk> is of course potentially at better biomarker in this normal data accumulating to suggest that that may be true with novel Immunotherapies again, I'm not referring here to chemotherapy or targeted therapy. There we understand that the value of resets that novel immunotherapy is a different beast for which <unk> radiology was not.
Devised.
So Cte DNA looks very interesting.
The regulators are paying attention now there is of course, an endpoint between Cte DNA in overall survival, which is progression free survival the concern about using standard PFS.
Regular resist is that you will miss classify patients and lesions will expand because of T cell proliferation that that will be classified as progressive disease per resist.
Even though actually the patient is doing very well and that is clearly a real concern with what we're doing and you've seen from some of our images in the phase. One study that we presented that we observe expansion of lesions followed by a contraction cavitation and shrinkage. So we've clearly observed pseudo progression radiological <unk> with the.
<unk> therapy. So we're nervous about PFS with resist now there is <unk>, which is developed specifically for immunotherapy.
It allows you to have one scan that shows pseudo progression.
Again, it wasn't developed for our immunotherapy.
It was developed for checkpoints checkpoints generally work in patients who already have T cells in the tumor that recognized neo antigens. So what we're doing is clearly proximal to that and therefore, maybe I resist is not yet calibrated for all purposes and for all therapy, we're exploring that in the phase II study that we are.
Currently running so we will generate data to answer all these questions.
Pull back is overall survival as you say.
And unfortunately in <unk>.
Just had a colorectal cancer overall survival is not a terribly remote endpoint median survivals in the two years or so.
Range and so this is an endpoint that can be used and of course, there is no crossover with the trial that we're running given the nature of the product so.
The answer to your question is as you think about registration OS is the conservative fallback.
PFS I think is a possibility if our phase II data suggests that it does.
Capture and deal with pseudo progression appropriately and upside would be that <unk> advances to a point, where it is widely recognized potentially as an endpoint for accelerated approval on the basis that it is to quote the legislation reasonably likely to predict clinical benefit in this case <unk>.
It would be likely to predict overall survival benefit.
So that's kind of the way, we think about endpoints in that context.
Great. Thank you for the thoughtful answer.
Yes, Thanks, Tom.
Thank you. The next question is from Sean Lee of H C. Wainwright. Your line is open.
Good afternoon, guys and thanks for taking my questions.
My first one is on late in the upcoming presentation at ESMO could you provide us more color on the <unk>.
Ah patients and what kind of results can we expect the type of results in terms of endpoints and biomarkers.
Yes. So this is a phase II study and it's relatively modest.
I'll be showing it with both the second generation so called slate Kers product will also remind you of the first generation slate version, one data as well so we'll be putting those together.
<unk>.
It's a regular phase III study and so it has a standard efficacy endpoint of response and that obviously can be measured using radiology recognizing the limitations that I've. Just articulated also of course, we are measuring Cte DNA.
And so we will be showing data primarily on lung cancer and colorectal cancer subjects as you would imagine all of the lung cancer subjects have previously been treated.
With immune checkpoint blockade.
And so we are in the post ICD environment for these data kind of ex Silversea, we're typically treating after full folks full theory.
Typically in the second or third line setting depending upon what the patient receives is frontline chemo. So youll get a pretty complete data set as well as of course always safety. That's what you should be looking out for.
Oh, great Thanks for that.
My second question is a bit of a high level one regarding the coral program.
A lot of discussion right now on the regulatory but they seem to be favouring at.
Annual.
Annual vaccine taking into the fall similar to the flu one so how do you envision <unk>.
Fitting into the paradigm or do you think that.
Because the longer lasting.
So the ability we could be able to exceed this paradigm.
Yes, I think it's.
Unsatisfying paradigm no one I think with regard the current model for influenza vaccination is a glorious success.
We have to try and predict which serotypes will be prevalent in the upcoming flu season, and our predictions are far from perfect, meaning that we often actually immunized with variance that end up not being particularly important in that future flu season.
And it requires annual boosts. So neither of those is particularly attractive I think we would all prefer to have less frequent vaccinations that have greater broader protective utility.
T cell component is obviously central to this question.
There are lots of indirect datasets, suggesting that T cell immunity to influenza does provide broad protection against severe disease, but it hasnt been tested prospectively.
In a phase III trial with a vaccine that elicits strong T cell responses to conserve the epitopes and measures.
Obviously, if we are to be successful in.
Developing these broadly protective vaccines, whether it's coronavirus offer influence it come to that matter you need to start running phase III trials, where you measure not just antibody, but also T cell response, so that's a key topic, obviously for us that we're quite focused on.
In terms of the antibody side.
There are some variance which appears to provide broader protection than others, and so theres a reasonable amount of data in the literature now, suggesting that with beta spike.
So it will be 130 501.
Variant the antibodies that you generate to beta spike provide broader cross reactivity Cross protection than for example, antibodies elicited by an <unk> variant Spike omicron appears to generate pretty narrow immunity, whereas beta is potentially broader acting now.
Two years of experience with Sars Cov, two to know whether we're going to see continued significant changes in the forms of spike that we're dealing with so it's a little early to answer the question on the antibody side, but I think the notion of having broadly neutralizing antibodies is not completely impossible.
Combine that with T cell immunity I think there is a hope for vaccines that do not require predictions and annual boost and then we will get free of this rather clunky paradigm that we're currently living with I think we can and potentially.
So I think we should and potentially can do better than the annual boost with a prediction as to what matters in the coming season.
Let's see.
Helpful. That's helpful.
Bye now.
Thanks, Joe.
Thank you.
Question is from current Jenkins of Goldman Sachs. Your line is open.
Hi, Good afternoon, everyone I'm curious since the last call update you provided on the winter have you got any specific regulatory guidance or an update on the regulatory path ahead for coral and if so could you just share any details there.
No we're not yet at Liberty to share.
Any regulatory conversations that we've had current obviously, what we'll put into public domain.
October as we said is a much more complete dataset at.
At multiple dose levels with Sam RNA.
As both a boost and also in vaccine naive subjects.
We'll be looking at an antibody immunity T cell immunity and react to Genesis Slash safety as well of course. So this is the foundation.
One, which will build but we're not yet at liberty to discuss.
Trial might look like.
Okay would you plan to go to regulators with that data in hand, then sometimes after you presented this fall.
Yes, obviously, we're not doing this for academic purposes alone I think there is unmet need for a.
Potentially second generation Sars Cov, two vaccine along the lines that we've discussed.
That's of interest to us.
Our phase III trials, the expensive trial exactly how expensive obviously does depend on the size and the design.
And so funding for that trial and having a partner together with the regulatory dialog are intermixed.
So that is our goal yes, okay.
Alright. Thank you and then as we think about the upcoming slate update in a couple of weeks.
Ah patients in this study screen for HLA subtype, and what are the potential implications for efficacy.
Of HLA subtype.
Yes, so they all screen for HLA subtype.
This is fundamentally different from for example, <unk> acid or <unk> I think it's fair to ratchet.
Okay with that.
Obviously software asset and diagnosis and royalty product.
Small molecule drugs that covalently bind to the <unk> 12 C.
<unk> form of <unk> by forming a covalent bond with assisting rescue. So this is sort of fairly well understood.
<unk> chemistry.
Therefore, those products work for and principle <unk> mutant irrespective of HLA background, because they just binding to the protein inside the cell.
Slightest different slate tries to generate an immune response to the fragment mutant K Ras that is processed and presented on the cell surface.
We're obviously trying to drive T cells that recognize that fragment. So it's fundamentally different and does require an understanding of HLA restriction.
The Bad news is you don't have to screen for HLA, which means this is not something you will simply give to everybody who has K Ras mutant disease. The good news is that we actually do have identified HLA allele present, K Ras <unk> C. G Trophy, <unk> deep and <unk> 61, H and so.
This one product can treat multiple mutant forms of <unk>.
So the population actually is quite substantial.
Estimate that somewhere between 10, and 15% of patients with colorectal cancer and non small cell lung cancer adenocarcinoma will be candidates for this form of immunotherapy against <unk> mutations.
Pancreatic cancer is a hard enough to crack and we've not done a lot of work there recognizing its challenges, but actually pretty much everybody with pancreatic cancer has a K Ras mutation. So that is quite a large population once we optimize the product and potentially prepare to move into pancreatic.
Obviously, the data you'll be seeing at ESMO will be focused as I said on non small cell and colorectal cancer.
Okay, great. Thanks.
Thank you.
Thanks Brent.
Thank you we take our next question from Omar.
Evercore Your line is open.
Hi, guys. Thanks for taking my question.
Quite surprised them pleasantly surprised to look at the data. My question is have you attempted to characterize the structure of these antibodies I'm trying to understand if there's like an FC tail that helps it gone for this long.
And also have you characterized the <unk>.
Subset of the antibodies elicited by Madonna and Pfizer, which do go out for six months and if theres any commonalities and what the structure of the antibodies I'm very curious about that.
<unk>.
I think everybody attempted to make comparisons of the nap tighter post boost the data you put out in January yours. It was like eight to 10 times increase some of the mrna datasets, where perhaps higher but to what extent was that re exposure boost.
That difference is driven simply by B cell memory response to taking the same thing for a third time versus taking a slightly different thing during the third shot and then finally.
If this regimen, where it would be truly truly competitive I got to believe you need to be at five specific and it could perhaps be an annual shot and I'm curious as you think about progression forward are you taking a wild type vaccine forward or do you think you actually do need <unk>, which is kind of a feedback FDA seems to be sharing with the.
Vaccine manufacturers right now thank you very much.
Thanks have a great to have you join us.
I'll ask you to answer questions wanted to but I'll take on question three festival. So in terms of the <unk> five.
As I said I think the.
The unity, you generate with omicron and Sip.
Siblings, such as ph will be five appears to be quite narrow and I think thats why.
There's a little bit of anxiety with a full campaign with boosting backwards as it were.
We're boosting the variance that was around before with low expectations, perhaps that it's going to be really helpful. Against whatever comes next because of course, we don't know what's going to come next but if we assume that it will be in some ways immunologically distant from the <unk> five.
The worry has to be the immunity, we're all going to get generated with another booster is not going to be that helpful.
For that reason of course, one can think about blended products, which indeed is what the first generation folks are doing.
And if you think about blending as I said beta looks pretty interesting as a partner for the blend because of the apparent breadth of immunity that it generates.
Of course, it also wasn't a.
That was particularly common globally and so there may be some relative global naive to take towards the beta variant.
It was common in South Africa, and a few other territories, but not not global.
I think there is some flexibility to think about.
What to put into the product going forward I agree with you, it's not going to be ancestral spike for sure I think a blended approaches is entirely credible.
You might pick something like beta for the reasons I've articulated.
Let's turn back to your questions wanted to which are both good questions Karen.
Yeah. So currently for our vaccine.
We are currently looking at the nature of the T cell response.
Not comparing it to the Madonna and Brian Tech, we don't have the serum samples there, but we are analyzing Alex central Accordingly, we still believe what I said earlier that the durability of the antigen.
Exposure the immune system exposure to the antigen types. These durable responses.
Analyzing the nature the nature of a day off.
We speak.
Thank you guys.
As your question on any anymore.
Yeah, I was just going to say congrats Celia [laughter].
Uh huh.
Thank you Mark.
Thanks, Hey, Matt and Andy Congrats you see here is heading towards.
Towards.
Right right.
Okay.
Thank you <expletive>.
Fashion.
I would like to turn the conference back to you Andrew Allen <unk> closing remarks.
Well. Thank you very much everybody. Thanks for joining us today I hope.
You found this call interesting and informative as you've heard we are very excited about the progress that we've been making.
We are a company that built step by step we're trying to innovate here both in terms of the design of our vaccines in the immunogen within them and we're using a novel technology and so we're building this fortress brick by brick and we bring to you today I think another step forward in this progress we look forward to updating you.
Further as our programs continue to advance and in particular with some some data at ESMO and then at I'd week in October so lots to look forward to in the next couple of months and with that we'll close the call. Thank you.
The conference is now concluded. Thank you for attending today's call you may now disconnect.