GeoVax Labs (NASDAQ:GOVX) Q1 2022 Earnings Call

0:00 Good afternoon and welcome everyone to the GeoVax First Quarter 2022 Corporate Update Call. I am Chuck with Course Call and I will facilitate today's call. With me are David Dodd, Chairman and CEO, Mr. Mark Reynolds, Chief Financial Officer, Mr. Mark Newman, Ph.D., Chief Scientific Officer, and Mr. John Sharkey, Ph.D., Head of Business Development. All participants will be in a listen-only mode. Should you need assistance, please signal conference specialists by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then 1 on your telephone keypad. To withdraw your question, please press star then 2. Please note this event is being recorded. I would now like to turn the conference over to Jules Abraham of Core IR, who will provide a forward-looking statement regarding this call and information herein. Please go ahead, sir.

0:52 Jules Abraham, Core IR Thank you, Chuck, and good afternoon, everyone. Please note the following. Certain statements in this presentation may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These statements are based on management's current expectations and are subject to uncertainty and changes in circumstances. Actual results may differ materially from those included in these statements due to a variety of factors, including whether GeoVax can develop and manufacture its vaccines with the desired characteristics in a timely manner, whether GeoVax's vaccines will be safe for human use, whether GeoVax's vaccines will effectively prevent targeted infections in humans, whether GeoVax's vaccines will receive regulatory approvals necessary to be licensed and marketed, whether GeoVax raises required capital to complete vaccine development, there is development of competitive products that may be more effective or easier to use in GeoVax's products, whether GeoVax will be able to enter into favorable manufacturing and distribution agreements and other factors over which GeoVax has no control. GeoVax assumes no obligation to update these forward-looking statements and does not intend to do so. More information about these factors is contained in GeoVax's filings with the Securities and Exchange Commission, including those set forth as risk factors in GeoVax's Form 10-K.

2:15 It is now my pleasure to introduce the Chairman and CEO of GeoVax, David Dodd.

2:21 Thank you and good afternoon, everyone. And again, thank you for participating in the 2022 first quarter update call. First quarter marked a transformational period for GeoVax in that we achieved clinical stage development status within the two priority areas of COVID-19 vaccine development and cancer immunotherapy. In addition, we added strong expertise and experience to ensure our ability to expand and accelerate are clinical development programs and the requisite activities through regulatory registration, manufacturing, and distribution. Our mission is to provide products that prevent or treat some of the world's most challenging infectious diseases and cancers by leveraging technology and collaborations that allow us to successfully provide life-enhancing products in a safe, scientific, validated manner. Our pursuit is to deliver safe, affordable products to improve lives worldwide, delivering increased value to our shareholders and providing motivating career development opportunities to members of our team.

3:26 We firmly believe that GeoVax can provide differentiated advanced vaccine and immunotherapies competing with and collaborating with other companies worldwide. We intend to successfully execute in this regard. We're pleased to have this opportunity to review our successful progress into phase two clinical development while securing critical resources in support of GeoVax's growth and development while also advancing our IND-enabling programs. The in-licensing of both GEO, CMO4S1, and Godeptin represented watershed events in the transformation of GeoVax as milestones towards potential significant value expansion of the company. CMO4S1, which we in-licensed exclusive global rights from City of Hope National Medical Center, is a next generation COVID-19 vaccine targeting both antibody and cellular immunity with the goal of providing more robust and durable protection than the current authorized vaccines.

4:30 Gadeftin is a cancer immunotherapy which we in-licensed exclusive global rights from PMP Therapeutics and the University of Alabama Birmingham. are currently being evaluated among patients suffering from advanced head and neck cancers and has already received orphan drug designation from the FDA. In addition, we're advancing encouraging internal programs on the path to IND final. In January, we issued a 2021 milestone report addressing the goals we established and communicated early last year. That update outlined our successful 2021 performance in executing upon those goals bringing us to the phase two clinical status, enabling our progress related to our internal programs while strengthening the organization with the expertise to accelerate our growth and development.

5:21 At the 2021 World Vaccine and Immunotherapy Congress last December, we reported results validating our COVID-19 vaccine approach of a multi-antigenic vaccine inducing strong antibody and cellular immune responses potentially providing more robust and durable protection beyond the current authorized vaccines. In fact, in a well-validated lethal challenge transgenic mouse model, our CM02 vaccine candidate, which is the first step towards a universal coronavirus vaccine, provided complete protection following a single dose, even in the absence of measurable neutralizing antibodies. For our knowledge, these results are unprecedented. I'll note that both our Phase 2 COVID-19 vaccine, CMO4S1, and our universal coronavirus vaccine candidate, CMO2, are each multi-antigenic COVID-19 vaccines, designed to strongly induce both antibody and cellular immune responses.

6:24 At that same scientific congress, we also reported further encouraging results in support of our Marburg and Sudan vaccines. Last week at the World Vaccine Congress, Dr. Newman further discussed the status of CM04S1 in our basis and support of our multi-antigen universal coronavirus vaccine. In January, we further strengthened our balance sheet and are currently well capitalized for at least a year. We anticipate further strengthening of our balance sheet during 2022, which will be addressed later by Mark Reynolds, our CFO. Our primary focus this year is to accelerate the recruitment and enrollment of our three Phase II programs. This includes our multi-site clinical trial in support of Gdeptin and our two clinical trials in support of CMO4S1.

7:15 Since acquiring the rights to Gdeptin, we have confirmed two additional clinical sites in the assignment of CatoSMS as our CRO partner responsible for leading the expansion and acceleration of the Gdeptin clinical program. Our focus on accelerated and expanded patient enrollment is actively underway with the goal to complete patient enrollment towards the end of 2022 or early 2023, followed by completion of patient evaluations perhaps by the end of 2023. Should the results be supportive of BLL filing, we'll likely follow shortly thereafter. In parallel with the ongoing clinical program, we are also engaged with the CDMO to prepare for commercial manufacturing. We are confident that the Godeptin Phase II program will be successfully managed by CATL-SMS and our clinical operations team with possible expansion of further additional clinical sites.

8:11 We're highly excited about the outlook and promise of Godeptin within advanced head and neck cancer where it has received orphan drug designation and has previously provided encouraging potential for such patients. In addition, there are promising opportunities relative to expanded use of gadeptin and other indications, as well as the GDEP technology in conjunction with other therapies and potential synergy with our own MVA-VLP tumor-associated antigen approach. We're looking forward to providing milestone updates throughout this year about the progress of our gadeptin program. Also during first quarter, we focused on the two phase two clinical trials in support of CMO4S1. This vaccine utilizes synthetic modified vaccinia anchor or MVA technology, similar to other vaccine programs under development at GeoVax.

9:05 CMO4S1 induces immunity to SARS-CoV-2 by stimulating the immune system to produce antibodies against SARS-CoV-2 that can block the virus from entering healthy cells while the immune system can also grow new disease-fighting T cells that can recognize and destroy infected cells. The vaccine includes both SARS-CoV-2 spike and nucleocapsid proteins. By inserting these proteins, the MVA delivery vehicle is able to drive the expression of both proteins within the body of the vaccine recipient, inducing immune responses. The role of the S protein is to elicit a neutralizing antibody response against the initial infection, while the N protein elicits or induces a T cell response to directly attack virus-infected cells, reduce viral replication, and reduce severity and clearance. Thus, the vaccine is designed to induce both neutralizing antibodies and T cell responses specific for the S protein and the N protein.

10:08 This vaccine design was implemented specifically to induce an expanded immune response to better combat and clear infection regardless of the circulating SARS-CoV-2 variants. This vaccine is the first step in the worldwide goal to provide a vaccine that gets ahead of the variants versus having to chase the variants. If successful, this vaccine will reduce reliance on the repeated administration of booster doses of existing vaccines. We believe that a multi-punch approach has the potential for providing a more robust and durable immune response and protection than the current authorized vaccines. We also believe that various high-risk populations, such as immune-compromised individuals, will benefit from such a two-prong approach.

10:55 CMO4S1 is currently being evaluated in two Phase II clinical trials. One trial is the first comparative study of an investigative Investigational COVID-19 Vaccine as the primary vaccine versus the current FDA-approved Pfizer vaccine in individuals that have received or are undergoing specific blood cancer therapies associated with transplantation or CAR-T therapy that suppress or severely reduce preexisting immunity to COVID-19 vaccines. Multiple clinical evidence has demonstrated and Val Dade that such patients fail to respond optimally to the current generation vaccine and we believe that CMO4S1 will prove to be the more potent vaccine because it is a multi-antigenic and delivered using the MVA vector. We believe this will differentiate CMO4S1 from the other vaccines by providing both a strong antibody response and a sustained and T-cell response in these patients who are still at high risk of severe COVID-19 due to their immunocompromised status.

12:05 The other trial currently underway is evaluating CMO4S1 as a booster for healthy patients who have previously received either the Pfizer or Moderna mRNA vaccines. We believe that providing a heterologous booster rather than a third or fourth or fifth shot of the same vaccine may provide more robust and durable immune response and protection. Heterologica's PrimeBoost immunizations are well studied in other fields such as HIV and are being evaluated in multiple countries using different COVID vaccines. We are working with the now combined Cato, SMS, and Formilon to oversee the acceleration and management of these two exciting clinical programs working under the direction of our internal clinical operations team.

12:51 Finally, the ongoing GFX effort to develop a manufacturing process based on a continuously growing avian cell line to increase production consistency and capacity will mesh with the clinical development activities and full development schedule associated with CM04S1 and CM02 vaccines. Now I'd like to turn the presentation over to Mark Reynolds, GFX Chief Financial Officer, for a review of our recent results and financial status.

13:19 Mark? Thank you, David. Okay, starting with our income statement, grant revenues were $82,000 for the first quarter of 2022 versus $111,000, $110,021, which is reflective of a wind down in both our grant from the NIH supporting our COVID-19 vaccine and our grant from the U.S. Army supporting our loss of fever vaccine program. As of March 31st of 2022, all currently available funds from this grant have been utilized. We do intend to seek additional non-diluted funding for our development programs in the future. And we've already submitted an application to the NIH in support of our MUC1 tumor-associated antigen cancer immunotherapy program.

14:09 Research and development expenses were $1.3 million in the first quarter of 22. versus 603,021, with the increase primarily associated with higher personnel costs, consulting costs, manufacturing costs for clinical trial materials, and generally a higher level of activity associated with the ongoing trials for CMO4S1 and for GDEPT. DNA expenses were relatively stable year to year, with $1.2 million in the first quarter this year versus $1.1 million last year. So overall net loss for the first quarter of 22 was $2.4 million, or $0.34 per share, versus $1.6 million in 21, or $0.29 per share, again with the increase primarily associated with the ramp-up of our organizational infrastructure and other costs associated with the clinical trial programs.

15:07 Turning to the balance sheet, our cash balances at the end of this quarter were $16.3 million compared to $11.4 million at the end of the year. The change in the cash balances is reflective of a $4.3 million used in operating activities offset by proceeds from the stock offering in January with net proceeds to us of $9.2 million. Funding our three ongoing Phase II clinical programs is obviously the most significant use of our cash and is our top financial priority. I should note that the first stage, that is 10 patients of the Gdeptin trial, is being funded by the FDA through a grant under its Orphan Products Clinical Trial Program. So that does help somewhat in mitigating some of our near-term cash requirements. While we don't provide specific forward-looking estimates of the cost to complete our research programs, what we can say at this time is that our existing cash reserves are sufficient to fund our operations and our priority programs into the second quarter of 2023. We believe the advancement of these programs will create, of the data flow that we generate, will create an attractive investment opportunity for new fundraising activities later this year.

16:28 and I'll be happy to answer any other questions during the Q&A period. I'll turn the call back to David now.

16:34 All right, thank you, Mark. My colleagues and I will now answer your questions and joining us as we've mentioned earlier for the Q&A session are Drs. Mark Newman and John Sharkey, our Chief Scientific Officer and Head of Business Development respectively. I'm therefore turning the call over to the operator for instructions on the Q&A session. Thank you. We will now begin the question and answer session. To ask a question, you may press star then 1 on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. And to withdraw your question, please press star then 2. And at this time, we'll pause momentarily to assemble our roster. And the first question will come from Jason McCarthy with Maxim Group.

17:24 Please go ahead.

17:26 Hi, this is Joanne Lee on the call for Jason. Thanks for taking the questions. I wanted to congratulate you guys on the recent publication of the phase one data of O4S1 last month. As a reminder, could you just walk us through how the results from that trial have highlighted the vaccine's mechanism of action and its differentiation from current vaccine?

17:47 Sure. I'll ask Mark Newman to step in on that. Sure. I mean I think that it's fairly straightforward as David said that vaccine was designed to induce antibody responses and T cell responses with the primary antibody target being the S protein and then T cell responses would be generated to both the S and the N and we measure the antibody responses by enzyme linked immunoassay ELISA which is just total titers and neutralizing function and both of those are were readily detectable and at levels comparable to what you're seeing with the approved vaccines, plus or minus the error range. It's a fairly small study.

18:37 And then we're also seeing the T-cell responses, which we typically measure as cytokine production. They're what's called a type 1 response, which is the predominant effective antiviral response, whereas a type 2 response would be considered and more for allergies and things like that. So it's the correct type of response. The nice thing is we saw good responses at all dose levels tested. That was the dose escalation trial as most phase one trials are. It was safe at all doses and the lower dose was essentially as immunogenic as the middle and higher doses. So we've got some range to work with. Does that help?

19:23 Yes, great. That was helpful. So for your two ongoing programs, 40471, could you just give us any updates on timelines in terms of the enrollment status? And lastly, as a follow-up, if you could briefly touch on, given the way new variants have been emerging and driving a constant ongoing string of boosters with the same vaccine, could you just touch on the importance of getting new vaccines to market that have differentiated mechanisms and targets? Thanks.

19:54 Mark, you may want to comment on it, but I think Kelly McKee, Dr. McKee, our chief medical officer, may want to add some comments also on that. So I'll leave it up to you two to go, whoever wants to go first. Okay, well, let me start. So you've heard us talk for a year that we're not really chasing variants. You know, the Omicron was just a perfect example. predictable next generation variant, right? We're seeing immune pressure against the circulating virus and now the new variants are coming up and there's less and less protection from the neutralizing antibodies. And of course, the mutations are happening in the S protein primarily because that's where the antibodies are targeted.

20:44 So I think that we're in the right position. If you follow the field, you will have noticed that there was an open letter recently sent to the FDA commissioner highlighting the importance of T-cells and imploring the FDA to ask vaccine manufacturers to start looking at T-cell responses. And I think that made the Wall Street Journal, and we're there already. So I think we're in the right position. The world is starting to recognize the importance of a broader immune response. World Health, CEPI, everyone is stepping up and saying, well, we'd like something that is variant-proof. The terms universal coronavirus or cross-variant or pan-cervicovirus are all being bantered around quite a bit.

21:35 And this has been a core part of our program since the start. And so with the first generation with two candidates, one in phase two and one in animal testing, both proving to be highly immunogenic and effective in inducing types of responses. You know, we're well along the way with this first step towards making a very improved and a more potent next generation vaccine. Kelly, do you want to add something? Yes, hello everyone. Not so much on the scientific side, but I can help out a little bit with the status of the clinical trials.

22:23 As you may be aware, our study in the immunocompromised population, the transplant trial, the study design is somewhat complicated, but I will say that we've enrolled patients in all of our different cell therapy cohorts. And we're sort of in the process of completing the safety lead-in phase in those cohorts. And for one of the cohorts, we're just about ready to transition into the blinded portion of the trial to compare against the Pfizer vaccine. Now one of the challenges that we've faced with that trial is the evolving therapeutic landscape for immunocompromised patients.

23:18 And so we've been, it's been necessary for us to sort of modify the protocol progressively to ensure that we're compliant with the standard of care for vaccination of these patients. between the sort of regulatory timelines connected with protocol amendments and so forth. The enrollment has been not quite as fast as we would like, but it's still progressing pretty well. The Healthy Volunteer Study, a similar sort of situation. It's a more straightforward trial, but again, in order to sort of keep to comply with the current practice of boosting healthy individuals. We're modifying that protocol to enable more aggressive enrollment, and we're very hopeful that that's going to pick up very quickly as well.

24:25 Got it. Thanks again for taking the questions. Thank you. The next question will come from Jeffrey Cross with Crystal Research. Please go ahead.

24:37 Thank you very much. David, it looks like, and this might be either for Sharkey or Newman possibly, but, you know, looking at gadeptin, I realize that there's a large focus in the marketplace on the COVID vaccines, but gadeptin seems to have incredible potential. When I was looking at some of the scientific research on this, you know, in conjunction with the checkpoint inhibitors, it seems to have interesting enhanced performance of the checkpoint inhibitors. Can someone expound a little bit about that? And secondly, can you provide an update on the status of the trial as well as some of the opportunities that I think lay ahead of us? Those are the first couple questions.

25:21 Okay, thank you, Jeff. John, why don't you take the first part, and then Kelly can give an update on the progress on the clinicals. or Mark Newman, would you? I don't know if John's still on. Well, yeah, I can start. I think John's muted probably. So, yeah, we're familiar, obviously familiar with the checkpoint inhibitor story. And I think that any product that can make the checkpoint inhibitors work better against solid tumors, particularly adenocarcinomas, has great potential.

26:09 So that's not part of the initial focus, but it is something that is being evaluated by a collaborator at Emory University. And there's a lot of interest in the field with combining all of these different products with checkpoint inhibitors, comparing them with standard of care, essentially. I mean, that's when we look at the cancer market and the approach. Everything is in addition to standard of care. So I don't think that the vaccines would be anywhere near as exciting, nor would these other types of products be anywhere near as exciting if you couldn't plug them in with the checkpoint inhibitor. So ideally, the goal here is the gadeptin will kill tumors.

26:54 And we presented this before. And as the tumors are dying, you release neoantigens. And the neoantigens are the basis of a vaccine.

27:02 So it's an autologous vaccine concept. We're not the only one that has looked at this, and there's a lot of literature out there on that, but it's not the lead on the program right now, but it is something that's being investigated.

27:20 Let me just see. John, are you there, or would you like to add something? If not, I'll ask Kelly to update on the clinical program. Kelly? Sure, no, I guess John's having trouble with his audio. Now, the clinical program, as David indicated in his opening remarks, we're sort of, as we've transitioned the IND over to GeoVax, we've expanded the trial from the original single site at Stanford and added two more study sites, one at at Emory and one at Thomas Jefferson University in anticipation of being able to accelerate the enrollment.

28:13 At the present time, we're about halfway through enrolling our total target number. And just as soon as we get all of the regulatory pieces back in place, which shouldn't be too much longer from now, we should begin Well, we've already got a couple of patients actually identified as potential candidates, but we should begin re-enrolling and finishing up that trial very quickly.

28:49 Thank you very much. And lastly, recently there was a letter signed by about 100 scientists, one of which was, I believe, one of your consultants. Can you talk about the significance of that, as well as the fact that so many people seem to be, I won't say jumping on the bandwagon, but providing support, which is congruent with your thoughts on many aspects of the science? David?

29:13 Sure. Now, Mark, you want to mention about that? Because that's one that Don Diamond, who led the development of CMO4S1 out of City of Hope, he was also a signature on that correspondence. Yeah, sure. I missed the letter I referred to just recently in an earlier question. So this is a number of immunologists or medical professionals working in the vaccine field that recognize that focusing solely on antibodies is an issue. And the issue is that that's not the total immune system. The immune system involves a complex, coordinated A set of effector functions and antibodies are only a single one. I thought what was really interesting about the letters, they actually cite the fact that there were some deficits impacting how the FDA reviews, for example, pediatric use of vaccines because they're only focusing on antibodies.

30:14 And in fact, maybe had they had rolled in a T cell function, a measure of T cells, they would have seen that pediatric use efficacy looks better. The world, the FDA is, you know, it's hard to predict, but there is a move in the field to start looking at surrogate markers more and more. And that means you're not looking just at efficacy. If you remember the initial trials, there were 30,000 plus patients in each of these trials for the products that were approved or got emergency use authorization. and, you know, you're looking for either they're infected and end up, you know, with symptoms or they're not. It's classic efficacy.

30:59 It's now recognized that placebo-controlled, blinded efficacy studies like that just aren't the way to go as we move forward, you know, attacking the new variants and adding new vaccines. And so there's always a series of meetings that are ongoing every couple of months. Most of them run through World Health Organization, the Blueprint Series. where these types of topics are discussed. So I think that this letter just fits in with a lot of other things that we're seeing. And that is a recognition that we've now, we've got some place, we've got great progress, but now we have to move back or move forward with the next step. And that's going to include a more broadly based characterization of immunity and testing of vaccines that have slightly different functions.

31:48 I think, like David said, we had a meeting, a conference just last week, and the closing session was, you know, can we make a universal COVID vaccine? And, you know, the CEPI representative pointed out, well, you know, something that's variant-proof would be great. Something that, you know, stops the next spillover from bats would be, you know, tremendous. And so that's where we're moving. and that's going to involve T cells and that's where I think you're starting to see momentum.

32:20 I was just going to say that's what we're focused on as a very strong differentiated point is about the focus also on the T cells. I think that's where we'll be able to carve out some very important areas of opportunity for our vaccine. Jeff, you had asked and I was going to ask if John who I think has been able to rejoin us now. John, do you want to comment on some of the animal work done at Emory of gadeptin in conjunction with checkpoint inhibitors? Sure. Sorry, for some reason I was disconnected. But, Jeff, your question was about some of the results we're seeing. And what's been observed is if we take a humanized tumor that's resistant to to checkpoint inhibition and transplant that into a rat model in both the left and right hind quarter.

33:17 We then treat the left hind quarter tumor with gadeptin followed with fluoridaryl-B phosphate. So we essentially are just pulling that tumor apart. We then come back with checkpoint inhibitor. Not only does the left-hand tumor respond to the checkpoint, but the right-hand tumor, which never received the gadeptin, also now responds. and this is the hypothesis is releasing neoadjuvants and other things from the left-hand tumor as it's destroyed and that's now sensitizing or messaging the right-hand tumor. And the way the tumors talk has been known for a long time. If you recall back many years ago, one found that if you had metastatic disease in a model and took the primary tumor out, all of a sudden the meds would grow.

34:05 So we know these tumors can talk to each other. Preclinical data, highly interesting because it does lead that it would carry over into clinical trials. You would now have a treatment that could address solid tumors and their meds and would not need to be needle accessible, only what some of the tumors would need to be. So very interesting.

34:30 Thank you, John. That's very impressive. Thank you. and I guess my last comments on COVID, it's more of a comment than even a question, but if there's anything that you expound upon, it'd be appreciated. Having two members of the family that I know who both are going through chemo and had really nasty, one is still going through a really nasty bout with the COVID, obviously because their compromised immune system. I would think that one of the targets, just not looking at COVID vaccine, everybody talks about a different approach, but I would think these people who have compromised immune systems that the multiple antigen approach would really help those individuals. And while it's not something that people focus on in the marketplace, obviously, there are a tremendous number of people suffering from cancer and going through chemotherapy who are subsequently getting COVID. And unfortunately, a significant number of them are dying.

35:25 Kelly, would you like to comment on that? Well, you're exactly right and I think the literature is replete with data to support the fact that immunocompromised, particularly severely immunocompromised individuals are much more susceptible to developing severe disease and dying from COVID infections and that's precisely why We feel that the CMO4S1 vaccine offers, at the current time, a unique option for protecting these people from COVID infection. Now, of course, it remains to be seen whether our hypothesis holds true, but at least in theory, if we can stimulate T cells to a degree that will, you know, provide sort of functional protection against the infection, against disease once these patients are infected.

36:37 We think we've got something very important to offer.

36:40 Yeah, I agree. Thank you very much. Thank you for the answers and thanks for the updates. Can I add something? Yeah, go right ahead, Mark, Mark Newman. I've got a paper on my desk. The title is CD8 Cells Contribute to Survival of COVID-19 Patients with Hematologic Cancers. And there's a sentence in here that points out cancer patients have increased risk of severe COVID. Estimated case fatality rate of 25%. That's 10 times the general population. This is a big meta-analysis. So it's clearly a focus that needs to be addressed and One of the things that people keep forgetting is that this MVA vector we're working with was developed as a super safe smallpox vaccine that is highly effective in populations like immunocompromised.

37:29 So it's really a T cell and an antibody driving type of vector with probably more T cell power than the other vectors. We really do think it's a good fit for these immune-compromised patients, and not just cancer patients, but people that are older, all sorts of immune-compromised situations.

37:53 I agree. Well, thank you very much for the updates. Thank you. Thank you. The next question will come from Michael Akunowicz with Maxim Group. Please go ahead.

38:07 Hey, guys. Thank you for taking my question. So I'd like to ask on some of the differences in the approach between CMO4 S1 and CMO2 that makes one a variant proof and the other a potentially universal coronavirus vaccine. So can you talk a bit about the targeting strategy for those two different vaccines?

38:41 Sure. Mark Newman, do you want to discuss that? Sure. I can address that. So the basic similarity is multi-antigen. So we're mixing the antibody target, the S, with another structural protein. Now, these were developed initially independently. So one was City of Hope. That's the O4S1. So that's S plus N. And then our internal program is S plus M, which is membrane and envelope. And those are the components that are required for the basic components required to have the in vivo virus-like particle assembly, kind of the basics of the GeoVax platform.

39:28 So the in-licensing, I mean, it was in-licensed because it was very similar. It was in clinical trials, and we viewed it as a first step. and that's phase two. Whereas the other program is in research. And just my own personal preference, we're not going to mess with the phase two product right now. It is what it is and we want to see where we can take that. And so we'll do more of the basic research with the CMO2. That's just in animal testing right now. So that's the one where we can add additional proteins. We'll see how many you know, different products, viral gene products that we can put into this vector to really broaden the response even more. Again, if you follow the field, there's a lot of reports coming out now about people that have been exposed to other coronaviruses.

40:20 They cause colds, you know, just they're not deadly. And these have induced T cell responses that help protect to some degree against COVID. So there's a continuing development of more and more data now showing that you're getting these kind of cross-reactive T cell responses that will add to protection. So that's the kind of work that's being done with the CMO2. But again, that's just in the mouse model right now.

40:52 All right, thank you. And then I'd also like to follow up if you could discuss some of the difficulties of conducting A COVID trial at the moment, just given where we are in terms of cases and how the fluctuations seem to be largely driven by emergence of new variants.

41:17 Sure. I'll make a comment and then, I don't know, Kelly, maybe you'll pick up from there. I would just say that my observation is that conducting clinical trials now versus, let's say, a year or two a year and a half ago, is challenged by the fact that we do have other vaccines out. We've got therapeutics out. Standard of care is evolving. And yes, you also are seeing continued evolution of this virus and the emergence of new variants of concern. Kelly, do you want to pick it up from there? Yeah, sure. I think this speaks to some of the comments that Mark Newman made earlier. around the need for us to sort of evolve thinking around what constitutes a surrogate marker for vaccine efficacy.

42:14 And back in the days where we could evaluate protection by a clinical response, that is is not only increasingly more difficult, it's nigh onto impossible. And so now we're faced with the dilemma of what sorts of markers do we utilize in order to demonstrate that a next generation vaccine be used as a primary vaccination or as a booster will, what kind of marker will be required for us to demonstrate that we've got sort of a better mousetrap?

43:02 You know, I think that, you know, the study designs themselves are probably pretty apparent. I mean, there'll be sort of non-inferiority types of comparisons to be made against existing authorized or licensed vaccines. But, you know, what measures we will use to compare against these current vaccines sort of remains to be resolved. I think our expectation is they're going to be, as Mark indicated earlier, they're going to be an acceleration of talk and discussion with regulators to resolve this issue. You may be aware that The NHRA, the regulatory agency in the United Kingdom, recently approved Valneva's COVID-19 vaccine on the basis of a serologic marker, a non-inferiority against the existing AstraZeneca vaccine.

44:08 And I think that's probably just the first in a number of regulator thinking in the are the first in line for thinking by regulators about how to approach this problem.

44:26 And I would add, Michael, that if you think about what GeoVax is focused on as a strategy, we're looking to be able to differentiate, and we believe that CMO4S1 may well demonstrate this, is these populations, as we've been talking about, immunocompromised. That represents, depending on how you define it, but if you take people being treated for various cancers or dealing with that, people who have genetic conditions, multiple sclerosis, who have weakened immune systems, people who have organ transplantation on immunosuppressive drugs, the very elderly, people with strong comorbidities. We begin talking of anywhere 10 to 15 million patients that are out there that clearly are not being adequately served by the existing vaccines.

45:18 And then if you look at the opportunity, which are niche markets but very valuable and important ones from the standpoint of the patients and the size of those, the opportunities, but at the same time, in a greater sense, is this need to have boosters that give greater durability because we continue to see and many more. So we think there are a lot of areas that need to evolve. Clearly how the discussions about how to evaluate and measure those, as Kelly was just talking about, is absolutely critical and that's going to evolve significantly also.

46:10 All right. Thank you very much. I really appreciate your insights. Thank you. This concludes our question and answer session. I would like to turn the conference back over to Mr. David Dodd for any closing remarks. Please go ahead.

46:25 Okay. And thank you, everyone, not only for participating in this conference call, but also for providing some very good, insightful questions and giving us an opportunity to discuss why we're doing what we're doing and what we're anticipating. we might well see coming out of the clinical end. But our focus is clearly, as we said, it's now on execution and reporting updates and progress for Godepton, CMO4, S1, CMO2, and our other development programs, as well as updates on expansion of our capabilities and resources. As I noted at the beginning of today's presentation, our pursuit is to deliver safe, affordable products to improve lives worldwide. The products that get vaccines and immunotherapies that can be not only delivered but administered and utilized and wherever they need to be.

47:17 And increasing value to our shareholders and again, providing motivating career development opportunities for the members of our team. We also want to acknowledge and thank our board of directors, our staff, and the many other parties that continue to support, assist, and advise us towards achieving success. For us, it's a great pleasure to be able to give you these updates and hopefully excite you about our company and for being a part of this team. So have a safe and enjoyable day. This concludes our conference call. Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.