Welcome to the Matinas BioPharma Third Quarter 2022 Results Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to Dr. Ankit Bhargava, Investor Relations Representative for Matinas BioPharma. You may begin.

Thank you, Dagmar. Good afternoon, everyone. And thank you for joining the Matinas BioPharma third quarter 2022 results conference call. Earlier this afternoon, we issued a press release with our financial results along with business updates. The release is available on the Matinas BioPharma webpage under the Investors section. There are slides accompanying today’s presentation, which are available by joining the webcast through the Investor section of the company’s webpage. Speaking on today’s call will be Jerry Jabbour, Chief Executive Officer; Dr. Terry Matkovits, Chief Development Officer; Dr. Terry Ferguson, Chief Medical Officer; and Keith Kucinski, Chief Financial Officer. We also have Mr. Thomas Hoover, Chief Business Officer, available to answer questions during our Q&A section. At this time, I would like to remind our listeners that the remarks made during this call may state management’s intentions, hopes, beliefs, expectations, or projections of the future. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the Safe Harbor provisions of federal securities laws. These forward-looking statements are based on Matinas BioPharma’s current expectations and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from those contemplated by such forward-looking statements are discussed in the periodic reports Matinas BioPharma files with the Securities and Exchange Commission. These documents are available in the Investors section of the company’s webpage and on the SEC’s webpage. An archive of this call will be posted to the company’s webpage also in the Investors section. Following the company’s prepared remarks, we will open the call for a question-and-answer session. Now I will turn the call over to Jerry.

Thank you, Ankit. Good morning, everyone, and thank you for taking the time to join us today. This afternoon, we will review our third-quarter financial results for 2022 and provide some highlights of our recent progress. We have departed from our normal filing schedule and call timing for this quarter. So I thought I would begin by providing some quick context to explain this change. First, we have seen that there is considerable competition for analyst and investor attention with the early morning calls. We wanted to provide an opportunity in a more convenient time for our analysts and valued investors to participate meaningfully. Second, Dr. Matkovits and I had been planning to travel to Uganda tomorrow in preparation for our Phase 3 trial and not returning until our Annual Meeting of stockholders set for Monday, November 14th. Despite that trip being postponed temporarily, we thought it best to stay on the schedule we had laid out for our analysts earlier this fall. So now let's get into it. During the third quarter and through today, we have achieved significant milestones for our company. We are a company proud to set and accomplish goals, and we are very proud of the list of milestones we have been able to achieve during 2022. At the very top of that list was the announcement of the interim results from Cohort 4 of our Phase 2 EnACT trial of MAT2203 in cryptococcal meningitis. Overall, EnACT was a highly successful Phase 2 trial, with patient survival results that are simply unprecedented for an oral therapy in this vulnerable patient population. Dr. Matkovits and her team, working closely with Dr. David Boulware from the University of Minnesota, delivered something many never thought would be possible: a clinical trial showing that oral MAT2203 could deliver effective doses of amphotericin B directly to the brain, achieving survival rates in excess of 90% and virtually eliminating the kidney toxicity historically associated with IV formulations of amphotericin, allowing for the safe use of MAT2203 for up to six weeks. We want to thank all of the EnACT patients, our dedicated investigators, and the entire clinical study staff in Uganda for their commitment to this important clinical trial. The feedback from key opinion leaders and infectious disease doctors at ID Week two weeks ago in Washington was fantastic, and we're aggressively preparing to commence our Phase 3 trial in cryptococcal meningitis in the first quarter of next year. Dr. Matkovits will go into more detail on our EnACT results and how we are well positioned for Phase 3 a bit later in the call. In addition to these impressive data in cryptococcal meningitis, Dr. Ashraf Ibrahim of the Lundquist Institute of the Harbor-UCLA Medical Center presented data at ID Week with MAT2203 and its impact on another deadly fungal infection, mucormycosis. Dr. Ferguson will briefly review some of the highlights from this promising preclinical study in vivo. During the quarter, we also received important feedback from the European Medicines Agency in the form of scientific advice and the granting of orphan drug designation by the EMA for the treatment of cryptococcosis. The EMA feedback was overall aligned with our FDA-supported plan for Phase 3, which positions this product for global development and registration. Positioning MAT2203 for global development and continuing to generate compelling data across invasive fungal infections couldn’t come at a more opportune time. As you may be aware, in October, the World Health Organization released its first fungal priority pathogens list to guide research and development. In its report, the WHO highlighted that invasive fungal diseases are rising at an alarming rate, particularly among immunocompromised populations. The underrecognized and emerging global health threat of invasive fungal disease is compounded by rapid emergence of resistance to many available therapies, resistance that generally leads to prolonged therapy and recurrent hospital stays. Despite this continually growing threat to human health, fungal infections receive very little attention and resources globally. The WHO classifies the identified fungal priority pathogens into three groups: critical, high, and medium. Both cryptococcal meningitis and aspergillosis were on the critical list, followed closely by mucormycosis on the high-priority list. With our Phase 2 success in EnACT, MAT2203 is well positioned to become an important weapon in the battle against cryptococcal meningitis. And we have also generated consistent and compelling preclinical data in both aspergillosis and mucormycosis, which could position MAT2203 to become an important part of effective treatment for many of these critical and high-priority fungal pathogens. We believe MAT2203 has many attributes of an ideal fungal agent. It's fungicidal, it's not prone to resistance, it's well tolerated and safe with no observed kidney toxicity despite use for extended periods of up to six weeks, and it has minimal to no drug-drug interactions. It's oral and delivered directly to infected tissues without exposing the body to toxic levels of drug in the blood. The profile for MAT2203 was one of the reasons we felt so comfortable initially studying its impact in cryptococcal meningitis, a severe invasive fungal infection with among the highest rates of mortality. Complicating treatment, this infection resides in the brain, making it very difficult to reach. However, for Matinas, this infection presented the opportunity to not only demonstrate that MAT2203 could safely and effectively treat this deadly fungus, but we could also show that our LNC platform could eliminate the historic toxicity of amphotericin B and carry this molecule across the blood-brain barrier and directly to infected tissues. With EnACT successful and in our rearview mirror, our confidence is extremely high that, one, MAT2203 is positioned for success in Phase 3 in cryptococcal meningitis and two, MAT2203 can also be used to treat other high-priority fungal pathogens like mucormycosis and aspergillosis safely and effectively, which informs the balance of our planned Phase 3 program. I'd like to turn the call over now to Dr. Matkovits to walk us through the MAT2203 EnACT data in more detail.

Thanks, Jerry, and good afternoon, everyone. I won't go into detail on the design of EnACT since by now everyone is familiar with our Phase 2 randomized open-label sequential cohort study evaluating MAT2203 in the treatment of cryptococcal meningitis. We announced data from Cohort 2 in September of 2021 and just recently at ID Week where interim data from the all-oral Cohort 4 were presented by one of the principal investigators of this study. EnACT received the Outstanding Abstract and IDSA Award from the Infectious Diseases Society of America, and we believe it reflects the impressive nature of the data and the unprecedented survival rates achieved with our oral therapy. Turning now to data from Cohort 4. Slide 9 depicts a survival scene with MAT2203 treatment in both Cohorts 2 and 4 versus the survival scene with standard of care IV amphotericin throughout the entire 18-week trial. Ultimately, survival is what infectious disease doctors and the FDA care about in this patient population. At each time point in EnACT, MAT2203 outperformed standard of care on survival. Importantly, EnACT was not powered or designed for noninferiority, but these data provided a great deal of confidence heading into our Phase 3 trial where the primary endpoint will be two-week all-cause mortality or survival with a key secondary endpoint of ten-week survival. As Jerry mentioned earlier, these are unprecedented survival rates among all oral therapies. The primary endpoint in EnACT was early fungicidal activity, or EFA, which is the rate of use clearance in cerebrospinal fluid. This is a direct measurement of the quantitative rate of antifungal activity at the site of infection and has become a well-recognized surrogate marker for survival. The prespecified target threshold in EnACT was 0.2, which is clinically meaningful and represents a robust degree of fungal clearance that is associated with enhanced survival. Importantly, and as pointed out on this slide, treatment EFAs beyond the 0.2 threshold have not historically resulted in any incremental benefit. Overall, MAT2203 achieved the primary endpoint and demonstrated robust early fungicidal activity in both Cohorts 2 and 4, which is why we believe MAT2203 was able to reach such remarkable survival rates in the study. Several patients with high baseline fungal burdens had noteworthy antifungal activity within the MAT2203 treatment arm, including one patient with quantitative cryptococcal culture as high as 915,000 CFUs per ml at the time of screening. Each of these noteworthy cases highlighted effective clearance during the induction period, a key demonstration of potent antifungal activity even in the most challenging of cases. This shows that our drug is having an immediate and high impact on the disease, a key observation for infectious disease doctors. These next two slides highlight the data from Cohort 2 and the design of our Phase 3 trial, which is predicated upon the design of Cohort 2 of EnACT. As a reminder, Cohort 2 was designed to evaluate MAT2203 as step-down therapy after only two loading doses of IV amphotericin. In Cohort 2, our two-week survival was 98%. 97% of patients achieved sterility, including all patients completing the induction course of treatment with MAT2203, and there were no breakthrough infections. MAT2203 was additionally safe and well tolerated with no kidney toxicity or electrolyte abnormalities observed even with six weeks of treatment with MAT2203. Our Phase 3 study replicates this cohort design, and we believe there should be a high degree of confidence in its success. We've chosen this design for a few key reasons. First, it's a derisked design predicated on 98% survival at our key primary endpoint with a 10% noninferiority margin against standard of care, which is a very comfortable goal. Secondly, in practice, most physicians treating patients presenting with cryptococcal meningitis or other deadly invasive fungal infections are most likely going to start patients on an IV therapy. Third, enrollment is likely to proceed faster with the IV loading doses available. And fourth, treatment guidelines will likely look more favorably upon this design, and MAT2203 could be included much faster than is customary, an important element for both physician adoption and payer acceptance. We're excited to initiate this Phase 3 study early in the first quarter of next year. We will expand our clinical sites up to five. And another important aspect of our derisked, FDA-reviewed adaptive design is the potential to add additional patients once enrollment has reached 75% to offset unforeseen patient deaths unrelated to study drugs. Enrollment is expected to take approximately 18 months with top-line data expected in the second half of 2024. Before I turn the call over to Dr. Ferguson, I would like to mention some of the progress we've been able to make on the CMC manufacturing side of MAT2203. As you know, we are partnering with Thermo Fisher Scientific for the commercial manufacturing and NDA readiness for MAT2203. I am pleased to report that due to both internal and external efforts, our transition to Thermo Fisher is proceeding on schedule and we are in a good position as we enter Phase 3. We are intent on doing everything within our control to ensure the successful development, registration, and commercialization of this important product for ourselves and prospective partners around the world. I will now turn the call over to Dr. Ferguson for some additional color on our MAT2203 program.

Thanks, Terry. Building off of Jerry and Terry's comments, we are positioning MAT2203 as an ideal antifungal agent with key value propositions of longer-term oral administration and avoidance of significant kidney toxicity. The capability of our LNC platform to both preserve the efficacy and fungal killing power of amphotericin B, while at the same time making it convenient and safe for patients, is incredibly important. While we are beginning our Phase 3 program with an indication for the treatment of cryptococcal meningitis, we've also developed a protocol outline for a Phase 3 study for the broader treatment of invasive fungal infections and plan to meet with the FDA to discuss this in the first half of 2023. Our ultimate goal is securing multiple orphan indications for MAT2203, maximizing the available regulatory exclusivities while also positioning this drug to be used as broadly as possible in the treatment of those WHO-identified priority fungal pathogens. Additionally, we believe MAT2203 has important potential applications for the prevention of invasive fungal infections, especially in immunocompromised patients, such as leukemia patients and transplant patients. Underscoring these plans are data we continue to generate in support of potential broader use of MAT2203. As Jerry mentioned earlier, Dr. Ashraf Ibrahim of the Lundquist Institute of the Harbor-UCLA Medical Center presented MAT2203 data for the treatment of invasive mucormycosis at ID Week. This late-breaking study demonstrated impressive in vivo efficacy of MAT2203 in treating two different strains of mucorales in immunosuppressed mice, with prolonged median survival time, enhanced overall survival, and significantly reduced tissue fungal burden of target organs, including lung and brain, comparable to that of ambisome conventional IV amphotericin B, thus positioning MAT2203 as a potentially important clinical option for the treatment of these deadly invasive fungal infections. Overall, MAT2203 is being positioned for global success with significant projected US and global revenues. We've seen more partnership interest in MAT2203 lately, and recent deal activity in this space bodes well for the value we believe we have created in our MAT2203 program. I will now turn the call over to Keith Kucinski, our Chief Financial Officer, who will discuss our financial results.

Thanks, Terry, and good afternoon, everyone. Today, the company reported its financial results for the third quarter of 2022, which reflected a net loss attributable to common shareholders of approximately $5.5 million or $0.03 per basic and diluted share compared to a net loss attributable to common shareholders of $6.8 million, or a net loss of $0.03 per share, basic and diluted, for the same period of 2021. The reduced loss resulted from the company recording $1.1 million in revenue during the current year period from its research collaboration with BioNTech SE, along with a slight decrease in operating expenses year-over-year. Cash, cash equivalents, and marketable securities at September 30, 2022, were approximately $33.1 million compared to $49.6 million at December 31, 2021. Based on current projections, we continue to believe that cash on hand is sufficient to fund planned operations through 2023. I will now turn the call back over to Jerry to provide some pipeline updates and concluding thoughts. Jerry?

Thanks, Keith. I did want to provide an update on our pipeline program since I know many of our investors are following these closely. First, and most importantly, our licensing discussions with BioNTech remain ongoing. The potential for the oral delivery of nucleic acids is extremely large, and we want to make sure we are putting our company and our shareholders in the best position both near and long term. Happily, our research collaboration is progressing well, and we have learned a lot about our technology and its application to nucleic acids over these past few months. We are diligently working together with BioNTech to commence in vitro and in vivo studies as soon as possible. Ultimately, we are both looking to increase the overall probability of success for these studies, and for each of us, there are a lot of steps along the way. On the licensing side, I have stated numerous times publicly that we are looking for the right deal and are prepared to make a fair deal for access to our LNC platform. We look very favorably at the precedents in this space and are also gratified to see a lot of interest from other third parties. We continue to believe that a deal with BioNTech makes sense for both companies, and are optimistically working toward that goal. We hope to have an update on this prior to year’s end. The other thing I want to highlight is that we have consciously chosen to slow down development of MAT2501 to allocate resources judiciously in these uncertain market times. While we continue to believe in the opportunity for the first oral aminoglycosides, we want to prioritize allowing some of our potential non-dilutive and inexpensive financing options to materialize and/or mature before moving into a Phase 2a study with that drug. In the short term, we believe advancing MAT2203 into Phase 3 and focusing our other efforts on platform expansion provides the greatest return for shareholders. In looking at our overall financial picture, we continue to push forward from a position of relative strength. Unlike many small-cap biotech companies, our enterprise value is far in excess of our cash, which we believe represents the market’s belief in our LNC platform and its considerable potential. While we do believe we continue to be undervalued, a cash runway into 2024 and multiple short-term opportunities for non-dilutive cash influxes position us to capitalize intelligently as we advance our products and technology. We have always been good stewards of our resources, and we will continue to protect our shareholders’ interests. We will continue to be thoughtful about how we extend our cash runway. And we believe that there are several ways this could happen in the short term, which would be viewed beneficially by our shareholders and the market. Overall, we are pleased with the progress we have made year-to-date, and there are several milestones remaining to be achieved between now and the end of the year, and then into 2023. Each of these could and should be viewed as potential value inflection points, and we are intently focused on executing to achieve one or more of these key objectives. Importantly, we have also used 2022 to expand our IP portfolio surrounding the LNC platform with multiple key new provisional patent filings, which we believe can further protect this technology and position us well internally and with partners globally. We have also taken the opportunity to increase awareness of our platform and its capabilities at multiple scientific and business development conferences throughout this year. Events such as the Next Generation Lipid Drug Delivery Conference, Partnerships and Drug Delivery, BIO-Europe Spring, the Mycoses Study Group Biannual Meeting, the mRNA-based Therapeutics Summit, the International mRNA Health Conference, and the American Society of Gene and Cell Therapy have given our team the opportunity to present and to engage with others to help them better understand our platform and how it potentially could solve some of the most challenging issues with drug delivery today. We want to increase our exposure and awareness at the same time we are doing whatever is within our control to advance our platform. This will conclude our prepared remarks for today. I will now turn the call over to the operator to facilitate a question-and-answer session.

Our first question comes from Greg Fraser with Truist.

The first question on 2203. Can you expand on the feedback that you heard from the doctors at ID Week? Was the feedback universally positive? Was there any data that the doctors were asking for like the sterility or the relapse status to better understand the clinical profile?

Greg, thanks for your question. I'll turn that right over to Dr. Matkovits and then if he wants to weigh in, Dr. Ferguson. But Terry, go ahead.

So two of the key elements of our clinical data for our cryptococcal study that really resonated with the physicians were survival and safety. So the ability to achieve survival rates that exceeded, and far exceeded, what has been seen with the available therapies was really resounding and really supported where they saw the benefit of our drug in the clinical setting. Secondly, the safety profile of our drug. Being able to treat patients for the first time with a longer treatment course of an amphotericin B product was really fitting into a high area of unmet need with patients suffering from invasive fungal infection. So those really were key attributes of our drug that highlighted the clinical interest. The opportunities to expand the use of our drug for the treatment of other deadly invasive fungal infections, such as mucor, aspergillosis, endemic mycoses, and the Candida infections, really indicates the potential for the first time to use an amphotericin product clinically for longer-term use in these other deadly infections.

Terry Ferguson, anything else to add there?

Just to add to that, I think that they were very happy with the data that they saw. There were not additional questions or holes that they found in the data. So they were very excited about it. You saw a lot of people taking pictures of the slides during the presentation. And I think the general air that I sensed was one of excitement around an opportunity to do things with amphotericin that hitherto were not really possible, to be able to give it orally, to be able to give it without worrying about the nephrotoxicity. So I think that the sense I saw was a lot of excitement and being very happy with the data presented.

And then, just to add to that, too, I mean, Greg, the one thing that jumped out at me the most was that instead of discussing the data themselves, the questions jumped to the 'how'. It was all about the mechanism of action and how our platform works, and trying to understand pharmacokinetics. That gave us the opportunity to talk about how this LNC platform encapsulates drugs in a solid crystal or keeps drugs out of the blood, allowing activated cells to go right to the site of infection. They were so impressed with the ability to achieve these survival data with an oral therapy that it jumped right to the 'how', and then it became a platform moment. I think that's the other thing that emerged at ID Week that generated significant interest.

So I'm curious about the Phase 3 study for invasive fungal infections. Will you be enrolling patients with different infections like mucor and aspergillosis, and how are you thinking about size and duration, as well as costs?

I would say, we've developed the protocol outline for that. Our plan is to enroll patients suffering from a variety of invasive fungal infections. There's precedent in this category for the so-called all-comer or basket studies. I think you'll see us focus on the major ones: mucor, aspergillosis, and maybe some of the more endemic mycoses. We're working on patient numbers now. We don't think it needs to be a huge study based on precedent in the space and the fact that we have demonstrated success in cryptococcal meningitis. We will obviously prepare well and submit a package to the FDA to have those discussions. That will be something that happens in the first quarter. But Terry Matkovits, anything to add to that?

I think Jerry, you hit it on the head. We intend to leverage what we've already demonstrated regarding efficacy in cryptococcal meningitis to allow us to conduct a more streamlined basket study for treating invasive fungal infections. We hope the FDA will be amenable to a more streamlined design that perhaps would allow us to conduct a smaller open-label study with external comparators, which would not require us to do a significantly sized study.

Can you use the same formulation in the study that you used in EnACT?

Correct, yes.

And would you initiate that study on your own or possibly wait for a partner to help fund it?

Given the interest in this asset and the fact that we're in an active process, our hope and expectation would be that we have a partner on board, particularly given the global nature of that sort of trial. This is not merely from a cost perspective but from a regulatory perspective, being able to set this asset up the right way from the beginning to check a lot of the regulatory boxes around the world. We anticipate that this would be part of the discussions we’re having with third parties.

I'll ask one more quick one and get back in the queue. But can you just remind us how long the standard treatment protocol with amphotericin is for mucor and aspergillosis?

Because of the toxicities associated with IV amphotericin use, it's typically restricted to one to two weeks of treatment followed by a step-down to an azole or echinocandins. However, those classes of antifungals have significant liabilities associated with their use, such as resistance and complicating drug-drug interactions. Just to remind us that these are immunocompromised patients who have significant underlying comorbidities and are on polypharmacy. The ability to treat with a safe alternative to a class that has significant drug-drug interactions and limitations of use due to those interactions really positions our drug to expand the opportunity with any amphotericin product.

Our next question comes from Robert Hazlett with BTIG.

I've got one or two. Congrats on the progress as well from me. Just with regard to the harmonization of the EU Phase 3, could you just go into a little bit more detail there? Are there any particular wrinkles in either additional work or work you're doing to make it amenable to an EU filing and acceptance?

One of the benefits, Bert, of us going early to the EMA was that we were able to get their feedback in time to incorporate it into our overall protocol planning for the Phase 3 for cryptococcal meningitis. So even though I would say the majority of their comments were aligned, there are some things they want to see, which we will be able to incorporate pretty easily. We think this is a study that we will be able to use to meet the criteria of both regulatory agencies, which is obviously a huge advantage. The benefit of Dr. Matkovits being proactive there, and going and getting that feedback means we can align everything at the start of Phase 3, without finding ourselves in a position of having to conduct smaller studies or other things to appease regulatory agencies.

And then you talked about being in an active process with regard to 2203. I’d love to just get your sense of maybe where you are and what a good deal might look like there. I know there are a thousand different ways to slice this, but is this something where you might consider a geographic carve-out, or is it something given this alignment that seems to be in place, you'd like to license the whole thing? Just a little bit more on the status and the types of deals that you might be considering.

Timing is everything in this business. There have been parties actively following the development of this drug for some time, obviously, their interest was piqued by Cohort 2, where you first saw the ability of this therapy to effectively treat immunocompromised cryptococcus patients. That interest has only increased since the data at ID Week and now with the World Health Organization's call for additional development. We've seen an increase in the prevalence of these fungal infections, particularly in immunocompromised patients, during the last year and a half, particularly since the pandemic. So it's a perfect storm. There is a lot of precedent in this space for deals done on a regional basis. You can look recently at things like Sidara or F2G in that space. I think we have a better product, one that has a broader spectrum and the ability to more effectively treat these pathogens. We want to be smart about it. We know we're not going to slow down this train because we have a drug that performs really well in these patient populations and that has the opportunity to stack indications. The interest is increasing, we would and are open to regional licensing deals, but we haven't discounted the potential for a global deal given the emergence and attention. We are focused on execution and being smart about how we fund. The NIH’s support of the Phase 3 for cryptococcal meningitis is a big reason we can afford to be patient. They will support a lot of the patient costs in that study. That is a big variable for us. Our team is working hard to inform partners. We have an active data room open, so we will be opportunistic and comprehensive in our outreach to all interested parties. Finding the right partner is a key part of our business objectives in the next two quarters.

And just following on that exact topic regarding BioNTech. I certainly don’t want to negotiate on a quarterly conference call, but at the same time, I'm interested if there's any particular ask or any particular hurdle that's being considered to affect the broader transaction?

I don't think there's an obstacle. For them, there are a number of things they need to consider. They're quite happy with how the research collaboration is progressing. We all know that their intentions have been pulled in a number of different directions. The parties are discussing value, and I think anytime you're trying to wrap your head around valuations, exclusivity, and the opportunity for oral messenger RNA, things can get complicated. These are mature, pleasant discussions. We always have a sense of urgency in everything that we do. But we are comfortable proceeding on a timeline that puts us and our shareholders in a position for the right deal. If we would have had the right deal two months ago, we would have done it. I think we're moving closer every day, and both parties believe it makes sense. It's a matter of crossing the T's and dotting the I's.

Our next question comes from Mayank Mamtani from B. Riley Securities.

This is Sahil Kazmi on for Mayank. Congrats on all the progress, and thanks for this really comprehensive update, and some of the interesting data we're seeing from EnACT. So maybe just starting there, as you think about the Phase 3 study, could you talk about some of your expectations for the different treatment arms in terms of the induction, consolidation versus standard of care, and put that in context of how significant that one-week loading dose of amphotericin is?

A couple of things we need to clarify. There won't be a one-week loading dose for the Phase 3, at least as far as the MAT2203 arms. We're talking about two loading doses. So over the first two days, patients will receive a loading dose, and then it will transition on day two to oral MAT2203 for the remainder of the 14-day induction period. The standard of care arm will involve seven days of IV amphotericin followed by fluconazole. We don't expect—and what we saw, both in Cohort 2 and was validated in Cohort 4—is that the loading dose was not responsible for the antifungal effect of our drug. I think one of the benefits of not stopping at Cohort 2 and going to an all-oral regimen in Cohort 4 is that it takes away the concern about the benefit of the loading dose. The loading dose provides reassurance for physicians at the beginning, and I believe it will expedite enrollment and has potential guideline impacts. But I will let Terry Matkovits elaborate on the two treatment arms. This study will involve approximately 270 patients, randomized two to one to the MAT2203 treatment arms, but Terry, could you discuss that in more detail?

As Jerry mentioned, our design for Phase 3 is replicating identically to what we did in Cohort 2, so the two days of IV amphotericin followed by a step-down to our MAT2203 arm. The final design of the study, which was collaboratively worked with the FDA, allows us to potentially secure for the first time a broader treatment indication for any amphotericin product specifically for a six-week treatment period. The way the primary endpoint is positioned focuses on two-week all-cause mortality, which we saw in our Cohort 2 data, performed better than standard of care. This same comparison will be tested in our Phase 3 registration trial, so we believe we are very much positioned for success. With two independent cohorts of EnACT, we have demonstrated better survival relative to standard of care. Recall that the overall statistical analysis will be for noninferiority. We need to demonstrate that we are noninferior to standard of care, which is a much lower regulatory bar. The ten-week all-cause mortality endpoint will also support these long-term treatment indications, which are likely to be a first-ever indication for any amphotericin product. Our Cohort 2 data saw numerical benefits, where we had 90% survival relative to 85% in the standard of care arm. This was similarly replicated in Cohort 4, so we believe we are well positioned to meet the criteria for both induction and longer treatment.

Additionally, that's one of the benefits of having multiple interactions with the FDA this past year, where we gained agreement for a longer indication of up to six weeks, primarily due to the safety data we generated and which they observed. This has also favored our treatment of mucormycosis and aspergillosis, both of which have treatment periods longer than two weeks. The FDA will be considering our data from crypto and that should impact the possibility for longer indications with a streamlined trial for invasive fungal infections.

And then maybe just a brief question on the BioNTech collaboration. Are you able to discuss in a bit more detail about some of the ongoing research and diligence that might have informed the preclinical models you're considering as you look to deploy some of the attractive features of the platform here?

Yes, we can't. We're not really at liberty to go into the specific nucleic acids or the targets. This is really two parties coming together, each with unique strengths and expertise: us with our ability to formulate and create novel formulations, and them with their unique messenger RNA format. There was a lot of learning that took place between the two groups regarding what they had previously used for delivery, what challenges they had faced, and the work we've completed with them on cell identification and uptake. This foundational work will position us to identify the best in vitro and in vivo studies going forward, so it has been collaborative and beneficial for us both.

Our next question comes from Matthew Coffield.

Thanks, and congrats guys on the continued LNC progress. Based on the Cohort 4 success and pivotal developments in cryptococcal meningitis focused on step-down therapy, what are your thoughts on the future usage of MAT2203 as a frontline therapy and how relevant do you see that ultimately being in terms of treatment benefits and the focus on platform expansion?

It's a good question because we get this query a lot from investors. Why are we discussing step-down versus starting with oral therapy. We've examined all these issues and had the opportunity to analyze the Cohort 4 data from an open-label trial, and we’ve discussed the Cohort 2 data extensively. We have also consulted with physicians and payers about their perceptions, which has helped us understand the treatment landscape. Ultimately, we keep returning to the same conclusion: using MAT2203 as step-down therapy checks a lot of boxes. It allows us to derisk our studies and align ourselves with physician practices, facilitating quicker study completion. It also diminishes questions that some physicians and patients may have about enrolling in the study. We believe this matches clinical practice. It's true that after Cohort 4, there's no question that we couldn't initiate it; however, it factors into every consideration as we position for success.

Now I will turn it back over to Jerry for closing remarks.

Great, thank you, Dagmar. We appreciate everyone taking the opportunity to join today. We look forward to your feedback. If this afternoon slot works better for our investors and the analysts, I think judging by our analysts' queue today and the participation I'm able to see online and calling in, I think this is a good thing. We look forward to updating you as we progress through the remainder of '22. We're going to close strong. We thank you for your support. One of the benefits we have as a small biotech company is the strength of our investor base. We have a very passionate and informed investor base who follows us closely. We'll continue to work hard on your behalf and check those boxes for the rest of the year and into 2023. Thanks, everybody.

Thank you. This concludes today's conference call. We thank you for your participation. You may disconnect your lines at this time, and have a great day.