I'm Chris LoBianco of the Calvin Farmer team, and I'm joined today by Novavax Senior Management.
Hi, I'm John Jacobs, CEO of Novavax. Nice to meet you all.
I'm Ruxandra Draghia. I head research and development in Novavax. Very nice meeting you all.
Hi, good morning. I'm Jim Kelly. I'm the CFO.
Maybe to get started, John, maybe we can kick things off with a high-level overview of Novavax and your new strategy post the Sanofi deal.
Thank you, Chris. Would love to. I'd like to welcome the folks in the back to join us up front if you want to. Just kidding. It's my dad joke, humor. Look, we couldn't be more excited to enter 2025, Chris. I mean, the last two years has been a remarkable journey, and I came to Novavax because of the technology platform. I believe it's the best technology platform in the world when it comes to adjuvant, our Matrix-M Adjuvant tech, and saw a real opportunity to impact global health in a very different way. In the last two years, it was really stabilizing the company, putting us in a much better financial position, and allowing us to refocus with our new strategy on what we love to do and what we're best at.
That is innovation and R&D based on our proven tech platform and additional business development and partnering. That is exactly how we intend to drive value going forward. The Sanofi deal was one of what we hope to be many and what we intend to be many going forward. In fact, just over the weekend, we had another top 10 pharmaceutical company. We are announcing that here for the first time at your conference, sign an MTA to experiment with Matrix-M across their pipeline. That makes now three top 10 by revenue pharmaceutical companies working with Matrix-M across assets in their pipeline and in their labs. We hope that those lead to further licensing deals for specific assets over time. It is very exciting to see that interest in our tech and going forward.
Just as a reminder for the audience, in line with that strategy, focusing on R&D, focusing on new partnering, and a lean, much more lean cost structure that Jim can touch on later in the discussion. Our priorities are simple. There are three priorities as we enter 2025 under the new strategy: optimize that Sanofi partnership and show we can be a partner of choice for sure. Number one. Number two, execute additional business development deals and partnerships and collaborations. Number three, advance early stage assets in our pipeline to initial proof of concept, which would further and facilitate more partnering and excitement in our tech platform. Lastly, what Ruxandra can talk about a little bit today, we are also working on improving Matrix-M, creating new formulations of our adjuvant. We filed several new patents last year.
We intend to continue to strengthen our intellectual property around that core asset for the company and expand its utility over time through experimentation and good science.
Great. Congrats on that new milestone. Looking ahead, can you just highlight the opportunity for the Novavax Sanofi partnership and, as a reminder, can you just remind us of the important milestones associated with that deal?
Yeah. Jim, do you want to cover some of the milestones?
Hey, certainly. Couldn't be more thrilled to have Sanofi as a partner. I'll break down the milestones across both the activity happening as they take the lead on commercialization of COVID, their ongoing work with not just one, but two COVID flu combinations that are aligned to their market-leading flu franchise, and the ability to work with our matrix to further advance their pipeline. Beginning with, I'll call it the overarching economics of the deal. There are $700 million in milestones that we're eligible to receive related to both advancement of COVID and combination products. We earned the first $50 million in the first quarter or the fourth quarter. That was linked to a pediatric database lock. As we look to 2025, important milestones to monitor are BLA PDUFA date for COVID-19.
We have a PDUFA date in April and the achievement of that BLA approval that makes us eligible for $175 million. As we transition both the U.S. and European markets later in the year, that creates eligibility for another $50 million in milestone payments. Finally, as we look to 2026, there's $75 million linked to transitioning tech transfer of manufacturing capabilities, so another $75 million. You drop to the combination COVID plus influenza vaccines. At the initiation of phase III of a combination vaccine with our COVID and Sanofi's flu, we're eligible to receive $125 million milestone. Upon first commercial launch in the U.S., another $225 million. We're not guiding to those timelines. We don't guide for Sanofi. However, incredibly large and meaningful milestones.
One of the things that I think Ruxandra is going to be able to share with you is a little update on where is Sanofi in their development. What have they said in their own words with respect to advancing their combination programs? In terms of other milestones to watch this year, A, their advancement of kick. In the later part of the year, you have Sanofi actually launching in the U.S. and other markets. Learning more about how they advance the commercialization of our vaccines.
We start earning royalties on this this year. The combination of milestones, Jim, right, and royalties over time significantly provides tremendous value just from this deal alone. On a longer-term perspective, if you're thinking about a 10-year horizon, a five, a seven-year horizon, et cetera, more and more opportunity growing just from the one partnership alone, and we don't intend it to be our last, but with Sanofi, they have unfettered access to our Matrix-M Adjuvant. For each new vaccine they may develop using Matrix-M outside of the combination with our COVID vaccine that they've now launched two clinical trials for with two separate combination assets that Jim alluded to tied to milestones and royalties.
In addition to those, any new vaccine they may develop using Matrix-M, we're eligible for up to $200 million per vaccine in sales milestones and then mid-single-digit royalties for two decades post-launch. When you think about the longer time horizon, you've got the near-term $700 million in milestones. Jim described $650 million of which are yet to be earned, roughly half coming from our new vaccine transfer to Sanofi, roughly the other half coming from their combination efforts with their flu vaccines and our COVID-19 vaccine in the near term. You have royalties starting to get generated this fall on our new vaccine, two additional, assuming success for Sanofi, royalty streams from their combination vaccines, and then potentially anything that comes out of their pipeline with Matrix-M, up to $200 million per vaccine in milestones and ongoing royalties for two decades.
Over time, this is layer after layer after layer, and I envision it like snowballs rolling down a mountain that eventually become an avalanche, right? One after another after another from this deal. We want to add in subsequent partnerships and collaborations that also have additional upfronts, additional royalty streams coming out from innovation. Again, we envision a future where our technology is amplified so we can touch billions of lives and spark that transformation in global healthcare. To do that does not mean we sit with one asset like a COVID-19 vaccine and go head to head against Pfizer. We have to open our arms and think a mindset of abundance. By sharing with others in this way, we drive value. We get to do what we love to do and what we think we are best at in our niche.
We think we can really open up tremendous value over time, much more so than from one asset.
That's great to hear. Not only does the company have the partnership with Sanofi, but you also have a wholly owned COVID influenza flu combo. Could you maybe elaborate on that and provide the latest update on that program?
Sure. Our intention, and I'll hand it over to Rex to give an update on the program, is to out-license and partner that asset. As we've said, part of our strategy is to take assets into early proof of concept phase and not invest the heavy economic burden into that to carry it through full phase three. With this last cohort, this initial cohort of roughly 2,000 patients in our phase III A, we'll generate the safety data and the learnings necessary to best facilitate a potential partner to take it forward through full development, licensure, and commercialization. That's the goal, but I'll allow Ruxandra to give an update.
Yes. As you might remember, we have started this first cohort of a phase III trial in December. Almost 2,000 individuals have been enrolled in this particular cohort. We do expect by mid-year to have the immunogenicity and also the safety and tolerability data. The immunogenicity obviously would provide us additional data and comparison to what is already available there. Very importantly, we will add to the safety database that can actually enhance our ability to compare the Matrix platform with other available adjuvants and platforms. We are very excited about that possibility. That entire set of data will then enable one of our partners who might be interested in picking up this particular program to really better design a phase three trial and demonstrate both the efficacy and the safety of the combination.
This cohort you mentioned, are these healthy adults? And kind of what's the comparator for the flu vaccine?
As you might remember, we do have a comparator flu vaccine. We have the kick arm, and we have a COVID actually arm, all compared to a placebo. There are, if you wish, comparisons very rigorous, both positive and negative in this particular first cohort.
Great. Among investors, there's some concern about the recent news from the administration. Do you view this as an overhang on the vaccine space?
Look, we are aligned with the administration on the goal of improving the health of all Americans and frankly, improving the health of people around the world. We are a global company. In that alignment, we intend to stay close and work with the administration. We believe strongly that vaccines can and will be a big part of that go forward. In fact, I think there was just a conference before this one addressing a lot of those points, and there is significant optimism about the position of vaccines go forward globally. No, we do not see it as an overhang. Certainly, there is radical change we are expecting from this administration and that we are seeing, but Novavax itself is going through radical change. We are diversifying away from, which are important, but seasonal vaccines only that need to be changed with strains every year, et cetera, et cetera.
We're investigating the applicability of our tech in areas like oncology and in other areas like neuroscience, even further removed from that, and in other types of infections, bacterial. I mean, we have a shingles vaccine that we're looking at. I mean, we feel that our tech has the potential to deliver equivalent efficacy, but certainly with potentially a better side effects profile. That's the potential of our technology, and we're beginning to explore that now.
Now, from a financial standpoint, the company has highlighted a path to profitability as early as 2027. What are the key factors to reaching that goal?
Certainly, certainly. One of the things with our update we gave to investors recently is we're outlining for them that vision because we know it's exceptionally important to understand this transition point that begins this year to an R&D-based and driven company that in turn is supported by the top line through partnerships, core to that, at least right now, the Sanofi agreement. You get big pharma type stability top line matched with innovation as we drive forward with our pipeline. Okay, what are the specifics behind being able to be profitable as early as 2027? One, because of the importance today of the Sanofi agreement, certainly advancing that kick program to market as early as, and by the way, we're not speaking for Sanofi, but as early as 2027, we described a break-even P&L profile, non-GAAP, of $225 million.
Coincidentally, that's also the size of the commercial launch milestone from Sanofi for their kick program. That's one of multiple levers we have to drive the profitability. As we get our cost structure down, that milestone is one. Two, we also outlined, hey, just based on the royalty rates and break-evens, we described how royalties from both Sanofi's sale of standalone COVID and sale of their combination vaccine or vaccines can contribute to that $225 million. Finally, we have expectation for more business development deals, both linked to the advancement of our early-stage pipeline and additional transactions linked to our matrix. Those are the three contributors of top line linked to us as we continue to drive down our cost structure.
That's very helpful. Novavax has substantially improved its financial strength through the Sanofi deal. Can you remind us of your latest cash runway?
Certainly. At the end of 2024, we had over $1 billion in cash and accounts receivables. Our goal is to maintain at least a year and a half to two years of cash at all times to ensure financial strength. The operational plan that we outlined as a part of our both forward-looking expense guidance plus revenue framework are consistent with that.
Maybe moving to the pipeline, you have four programs in preclinical development. Can you expand upon why you chose those four programs and maybe speak to why Matrix-M could really add to the value proposition of those assets?
Yeah, I'll make a comment first and then hand it over to Ruxandra for more detail on the pipeline assets. Since I joined Novavax two years ago, we've really rebuilt the company in many ways, resized the company, and also changed the culture and the way we work internally at the company. We added a new internal portfolio development committee of management, new processes on how we think about and filter decisions around assets that are quite rigorous that you'd expect to see in any top boardroom from a major global pharmaceutical company with that rigor and that quality. We put the decision-making through multiple filters, including a mix of both commercial and scientific. Where are the biggest markets in the world that have significant unmet need? What are the emerging competitive pipelines?
These are just examples, but in those markets, why do we believe we can win and provide an alternative there that would be clinically meaningful and relevant to that marketplace where you could earn significant market share and drive a lot of value and have a positive impact on global human health? All of those factors, as well as is this attractive to other companies? A core part of our strategy is partnering, generating further collaboration and partnership across the industry. How are we solving for others' pipelines and what would be interesting to other corporations as well? That, among many other filters, are used to make these decisions. We took quite a bit of time, energy, and effort to make these decisions and select bets.
One other point is that it's not just the four assets that everyone can see that we just announced in January in the pipeline, but Ruxandra's leading an effort incorporating machine learning, artificial intelligence. I know that's a buzzword we hear a lot in the industry, but we really are applying that specifically and with purpose in our early-stage discovery. We feel it takes timelines and can shrink them down and make us a bit more precise in what we're doing earlier on in our efforts. That's cost-effective and efficient for us. We're also finally working to expand the utility of Matrix-M, new formulations of our adjuvant, testing our technology with other platforms. How well can it work with mRNA, polysaccharide platforms, protein-based platforms? We believe Matrix-M has applicability across all of those. We're generating those proof points right now in our laboratory.
We're arming our business development team with that data. Under CDA, they're in meetings with global pharmaceutical companies. We can actually show those companies what we can do to improve their existing assets and also to help them potentially bring forward assets where they have failed or missed before and would desire to do so. Very exciting. It's not just about the assets. It's about proof points for our tech as a whole and strengthening our messaging with potential partners with scientific proof points. Rux, did you want to comment further on what's special in your mind as our leader of R&D on these four assets and what our tech might be able to do there?
Yes, thank you, John. First, starting with a little bit of the history of Novavax, we have delivered over and over again in the area of respiratory pathogens. That was the idea of first looking at something like the pandemic flu, H5N1. We have generated very exciting data in non-human primates. They are under review at a major, actually scientific journal. We hope to see those data printed actually very soon and also develop the platform so we can actually change very rapidly. We have tested it not only against H5N1, but a multitude of other flu strains to really again prove the breadth of immune responses that we can accomplish using the matrix and also the fact that we can cover really very old strains that were not actually present in the current vaccine.
We are actually taking that look of can we actually provide protection against a lethal challenge in an animal model, but also the breadth of protection that would allow a population that has previously been vaccinated with a flu vaccine or have had flu in their lives to really be protected if H5N1 is going to become a bigger problem than it is today. We have focused on an RSV combination, and I would like to underline the word combination. I know that there are RSV vaccines out there, but we think, as we've briefly discussed before this meeting, that combination vaccines are a way to go in the future. That is another element that we have envisioned to be doing.
Going to other pathogens, shingles is still a big problem, not in the least because the currently available vaccine, while very efficacious, has a tolerability profile that makes that about 20-40% of the population that gets the first dose doesn't go to actually take the second dose, which makes a lot of people that are undervaccinated or non-vaccinated. Using our AI machine learning, the new capabilities, we think that we can actually design antigens that could provide an equally effective vaccine, but more tolerable because of the matrix formulation. Finally, C. diff is a problem that we know. There isn't an efficacious vaccine that has been approved out there, and we are actually capitalizing on some of the work that has been done in the lab to, again, using this machine learning and AI to design better antigens.
For the work on Matrix, we do believe that new formulation can cater better, be tailor-made, if you wish, for oncology applications, for instance. Change the type of immune responses that we are generating in order to better adjuvate whatever oncology vaccine is out there. This is on the top of the work that John has mentioned, testing Matrix with different platforms.
That's really exciting. I know there's been a lot of investor excitement about the Moderna oncology vaccine. Hopefully we could get some more visibility on that in the next few years. Maybe looking at potential BD opportunities, what feedback have you heard from potential partners on Matrix-M, and what specific aspects of the platform have received the most interest from outside big pharma companies?
To me, action is one of the best forms of feedback. Getting another top 10 pharma to sign that material transfer agreement over the weekend was fantastic news for us. We do not intend to be done there. As companies start to experiment with what they hope to be their future portfolio assets and even existing assets potentially, they see how effective Matrix-M is in the lab. That turns to other conversations that we would intend turn into licensure and agreements that start to generate upfronts and royalties for the company and multiple streams. That is what we envision. That is what we intend to deliver. Until we do, we have not. Those are difficult things, if not impossible things, to project and give you timelines on.
That is what we call the surprise factor with Novavax that as we get these things, we will let you know. In between, you can take a look at the Sanofi agreement that Jim outlined. What we are doing is, if you think about the way we are restructuring the company and positioning it for success as a platform, innovative business that is focused on partnering and business development, we are squeezing our expenses down to that minimal core and a minimal core with the intention that just the Sanofi deal alone, assuming success, and not even on all of the potential aspects of the deal, but on the basic baseline aspects of the deal can get you to profitability as soon as 2027.
That alone provides a steady platform and engine where we're self-funding to drive additional innovation out of our pipeline with the intent of bringing these assets to early proof of concept and partnering them out with other organizations. In addition, we can out-license our current tech platform in the form of Matrix-M, where you've already seen now three top 10 pharmas engaging, starting with Sanofi and two others now top 10 in revenues around the world, experimenting with our Matrix-M and their pipelines with the intent, we hope, assuming success with their experiments, that that leads to potential licensing deals with those companies as well, with Sanofi as a model for that go forward.
You have the work we're doing with Ruxandra in the lab to create new formulations of Matrix-M to explore disease areas like oncology beyond infectious disease to further strengthen our patent suite and to generate tremendous opportunity going forward. Feedback, Ruxandra, we're hearing from partners on why do they love our science so much? Why are they interested in it so much at least?
I think that everyone in the scientific world realizes that there is not such thing as a magic bullet. While many of the platforms create a lot of hype at a certain point in time, we still have so many unresolved issues in the area of vaccines, in the area of infectious diseases. We need a panoply of different platforms and different technologies in order to cater to what Mother Nature actually is throwing to us. If one platform would have solved everything, we would have had by now a vaccine for HIV, yeah? We do not. Or for other infectious diseases. HCV is another example, is it not? I think that we need to maintain that scientific humility and think how we are going to contribute from our side to developing excellent science.
The answer very often is through collaboration, is through partnering, everyone bringing their best technology, and we put it together and something that is better than the sum of the parts is actually happening. This is why we are experimenting with matrix and these other platforms and asking the question, can we actually provide something that is much better than the sum of the parts?
It's so well said, Ruxandra. It ties right into our vision and our strategy, that mindset of abundance that we talked about before, that if we hung on to the tech ourselves and just used our platform and squeezed one or two assets out and compete with that, that's so limited as to what the possible potential of this technology really is to impact global health. By sharing it with other companies in a positive way, with a win-win mindset across multiple platforms, no one company has all of the answers ever. By partnering and opening our arms and our minds to more, we create abundance for everyone and win-win scenarios across the industry.
Great. We think that strategy makes perfect sense. Maybe in the final few minutes, can you highlight the key catalysts to look out for in 2025?
Look, and Jim, please build upon this and Rux, but I think in general, what to look for from Novavax, our first and foremost, aligned with our three priorities. First priority is optimize the Sanofi deal. So already in our hands, already tied to the potential for profitability as early as 2027 is continued execution on that, starting with our BLA. We have an April PDUFA date for BLA. Look for that with Sanofi. Look for Sanofi to share data, their readout on their phase two, phase one two trials, which got fast track from FDA, combining our COVID-19 vaccine with their two world-leading flu vaccines, right? We want to look for that. Look for the MAH transfers from us to Sanofi, which generate additional $50 million in milestones.
Look for potentially toward the end of the year, maybe into next year or so, but Sanofi to launch a full phase III trial with a combo, which leads to another $125 million milestone for Novavax. Look for Novavax to close additional deals to enhance existing partnerships, to continue to shrink down our physical footprint and our cost footprint toward those goals that we've shared with the investor community. We've shown we can do it before. Look for big swings in pieces of that again. One example at the end of last year in December, Jim was the sale of our CZ manufacturing facility, $200 million in cash for the company, and then also a reduction of roughly $80 million a year go forward every year on operating expenses saved. Look for us to do more things like that with our global footprint, right?
Look for us to share data from our emerging assets in the new pipeline in the second half of this year. We intend to do an investor day. Perhaps you can be part of that with us, Chris. That would be great. Where we share initial learnings from these four assets, initial data from Matrix-M and our experiments with new versions of Matrix-M, our experiments in oncology and across different platforms, et cetera. You never know when we might announce a new partnership or a new collaboration. We're working on that 24/7. We have a dedicated team to that. We're fueling that team with new data all the time on how our technology works so well with other platforms. It's our intention to do more. We can't predict that.
We can't tell you when, but look for us to potentially surprise you with more announcements in that arena as well. Anything to add, guys?
I think as we stand here today, the path to not only break even, but long-term value creation has never been more clear. We are looking forward to the meetings here today and ongoing with investors as they learn more and gain conviction around that. Specifically, what are the proof points, as John just outlined, where people can further see catalysts to drive improvement in our stock and value creation for patients around the world?
I am the geek, so I have to focus on data. I think that this year we are going to be able to share additional data that actually underpins what we have presented here today for all the platforms, for all the collaborations. That excites me enormously.
I'll close with this sentiment. It's not done until it's done. That's our mantra internally. We intend to prove our optimism and our intent. We intend to prove that out with action and by delivering for the investor community. Until we've done that, we haven't. We can share with you our excitement and our intent. We know we've got a proven tech platform and we're working with something very special here. We believe in the vision and the mission and the journey that we're taking the company on. We appreciate all of the investors who've given us their faith and their trust already. We promise to work really hard with all humility and keep our nose to the grindstone to not let you down. It's our goal to deliver. We'll do our best to do that each and every day.
A lot to look forward to and a lot to be proud of in the last year. With that, I think we're out of time, but I'd like to thank Novavax for being here.
Thank you, Chris.
Thank you.
Appreciate it.