Matinas BioPharma Holdings Inc (MTNB) 2021 Q4 法說會逐字稿

Hello and welcome to the Matinas BioPharma fourth quarter and full year 2021 results conference call. (Operator Instructions) As a reminder, this conference is being recorded.

I would now like to turn the conference over to Peter Vozzo, Investor Relations Representative for Matinas BioPharma. Please go ahead, Peter.

Thank you, Kevin. Good morning, everyone. And thank you for joining the Matinas BioPharma fourth quarter and full year 2021 results conference call. Early this morning we issued a press release with our financial results along with the business updates. The release is available on the Matinas BioPharma website under the investor section.

Speaking on today's call will be Jerry Jabbour, Chief Executive Officer and Keith Kucinski, Chief Financial Officer. We also have Dr. Terry Ferguson, Chief Medical Officer; Dr. Terri Matkovits, Chief Development Officer; Mr. Thomas Hoover, Chief Business Officer; and Dr. Raphael Mannino, Chief Scientific Officer who will be available to answer questions during our Q&A session.

At this time, I would like to remind our listeners that 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 investor section of the company's website, and on the SEC's website. And archive of this call will be posted to the company's website also in the investor section. Following the company's prepared remarks, we will open the call for a question and answer session.

I'll now turn the call over to Jerry.

Thank you, Peter. Good morning, everyone. And thank you for taking the time to join us. Today we will review our 2021 fourth quarter and full year financial results and provide a brief business update following the more comprehensive business update we provided in late January.

I would also like to take a few moments to expand on our stated strategic intentions of moving aggressively with our LNC platform technology into the delivery of nucleic acids, including messenger RNA, DNA and antisense oligonucleotides. We believe that the unique attributes of our delivery platform could position the team's LNC technology to become the next generation drug delivery platform for the intracellular delivery of nucleic acid.

And looking back on 2021, we are extremely proud of the significant progress that we made over the course of the year to advance our LNC platform technology highlighted by compelling clinical data from the first 3 cohorts of our EnACT trial of MAT2203. As you know, this trial is evaluating our oral LNC formulation of amphotericin B in the treatment of cryptococcal meningitis, a deadly fungal infection of the brain, which is especially problematic in immunocompromised patients, such as the HIV patients enrolled in EnACT.

We are extremely pleased to report that Cohort 4 is actively recruiting and continues to meet our enrollment expectations. As has been previously discussed, Cohort 4 is studying an all-oral regimen of MAT2203 during the 14-day induction period, followed by 4 additional weeks of oral consolidation therapy with MAT2203. Cohort 4 is comprised of 40 patients on MAT2203 and a control group of 16 patients receiving IV amphotericin B. This is an especially informative cohort of patients since the patients in the MAT2203 group do not receive any dose of IV amphotericin. And so it's a great opportunity to demonstrate the clinically meaningful impact that oral MAT2203 can have in these highly vulnerable patients.

We have enrolled 15 patients as of today, and all patients receiving MAT2203 are reported to be doing well. In fact, to date, all of the Cohort 4 patients who received MAT2203 have achieved sterility, meaning the absence of infection by the end of the 14-day induction period. It appears that Cohort 4 is off to a very good start, and we remain very optimistic that the positive patient experience and compelling clinical data will continue through the completion of this all-oral open-label cohort.

Enrollment in Cohort 4 is expected to complete in the second quarter of 2022, with availability of top line interim data anticipated in the third quarter of 2022. This past December, we met with FDA to discuss the data from EnACT and the pathway to a new drug application or NDA filing for MAT2203, focused initially on an indication for step-down therapy from IV amphotericin for induction treatment in patients with cryptococcal meningitis.

Based on those discussions and documented in the official minutes of the meeting, we plan to expand the current EnACT trial to include an additional cohort of patients, Cohort 5, which would include patients receiving MAT2203 as step-down therapy for induction following 2 days of IV amphotericin using a treatment protocol similar to the previously successfully completed Cohort 2. New features of Cohort 5 will include the primary endpoint and the non-inferiority margin, each of which will be discussed with FDA at our upcoming meeting. We believe that Cohort 5 will generate the confirmatory evidence FDA is seeking to facilitate an NDA submission in late 2023 or early 2024.

We have completed protocol design for Cohort 5 in close collaboration with Dr. David Boulware from the University of Minnesota and are scheduled to meet with the FDA early in the second quarter of 2022 to discuss specifics of the protocol. Our discussions will focus on the primary endpoint of 30-day survival, agreement on the non-inferiority margin and the size of the safety database necessary to support an FDA filing. Following feedback from FDA, we expect that Cohort 5 will commence in the second half of 2022, and based on current projections, take approximately 1 year to complete enrollment. Of course, this remains subject to FDA agreement on the above-mentioned key points.

Furthermore, our plans for MAT2203 as a safe oral formulation of amphotericin B go well beyond the treatment of cryptococcal meningitis and well beyond a purely domestic regulatory strategy, given the increasing interest from third parties in licensing MAT2203.

To support our partnering efforts as well as expand the global footprint for MAT2203, we are undertaking a number of important initiatives in 2022. First, we are preparing to submit a formal request for scientific advice to the European Medicines Agency during the second quarter of 2022. This is a key step in gaining regulatory advice outside the U.S. and the key strategic input for partners seeking to develop and eventually commercialize MAT2203 outside the U.S. We expect to receive feedback from EMA later in 2022.

In addition, preclinical studies of MAT2203 in candida auris and mucormycosis or black fungus, are scheduled to begin in the second quarter of 2022 to support potential label expansion into other dangerous invasive fungal infections. We know that amphotericin B has significant activity against these infections. And these studies are designed to show that our oral MAT2203 can have the same or perhaps even better efficacy, along with the picture of enhanced safety that seems to be emerging from EnACT. These studies, in turn, will support a potential registration trial in the treatment of a variety of invasive fungal infections with the ultimate goal being to position MAT2203 as the therapeutic of choice in the treatment of invasive fungal infections, which is projected to grow to an $8 billion market in the coming years.

Finally, in anticipation of a potential NDA submission for MAT2203, we recently selected and reached agreement with a leading global contract manufacturing organization to support the scale-up and commercial manufacturing for MAT2203. We believe this key relationship will support MAT2203 domestically and potentially globally and be another important consideration for a partner or partners seeking to develop and commercialize MAT2203 on a global scale.

Regarding MAT2501, our LNC oral formulation of the broad spectrum aminoglycoside antibiotic drug Amikacin, our single ascending dose study in healthy volunteers is ongoing, with data expected later in the second quarter of 2022.

Turning now to our current research collaborations. Our programs with Genentech, the NIH and Gilead continue to highlight the breadth and capabilities of our LNC platform. We expect to begin work on Genentech's third chosen compound in the coming months, and our second in vivo trial of oral LNC remdesivir scheduled to commence very shortly, with data expected in mid-2022.

Before we move into a discussion of our full year 2021 financial results, I would like to comment briefly on where we see the future of our LNC platform beyond the reformulation of small molecules. As we transitioned away from LYPDISO in early 2021, we focused on execution of the EnACT trial, which we believed would yield critical clinical data validating our LNC platform technology, highlighting the impressive efficacy and safety of an oral amphotericin formulation, while at the same time serving as a very important demonstration of how our LNC technology was able to carry drugs across the blood-brain barrier and target tissues that have been very challenging to reach with oral therapies.

Encouraged by these compelling clinical data and supported by a vast amount of preclinical data in the formulation and delivery of siRNA, DNA and antisense oligonucleotides, we have continued to significantly expand our internal capabilities, focused specifically on platform efforts to move aggressively into the intracellular delivery of nucleic acids. Since the middle of last year, we have added more than 15 new scientists and professionals, mostly PhD level, with people coming from companies like BMS and Merck and attracted by the potential of our LNC technology as a major step forward in advancing the capabilities for intracellular delivery.

We have established internal cell culture and nucleic acid formulation labs and initiated discovery programs based on the delivery of messenger RNA, DNA and antisense oligonucleotides. We are intent on further expansion of our LNC platform and establishing both an internal and external pipeline of drug candidates in the nucleic acid space. The unique properties of our LNC platform, including oral bioavailability, extrahepatic targeting, large payload capacity and improved stability and safety are supported by key preclinical data that differentiates our technology from both lipid nanoparticles or LNPs, and viral vectors.

Despite advances in treatments comprising nucleic acids, including the COVID-19 vaccines, safe and efficient intracellular delivery remains perhaps the greatest challenge to the effectiveness of these therapies as both LNPs and viral vectors have significant limitations. LNPs are limited in that they can typically only access the cell via clathrin-mediated endocytosis, followed by disruption of the endosomal membrane within the cell to gain access to the cytoplasm. LNPs typically are very inefficient and patients can also experience injection site adverse events and other toxicity, thereby limiting chronic or repeated use. LNPs cannot be delivered orally and are very unstable, requiring extreme cold chain storage temperatures to maintain their integrity.

Viral vectors, including adeno-associated virus, attempt to harness viral intracellular delivery mechanisms to facilitate fusion with the cell membrane and delivery of molecules into a cell. Unfortunately, viral vectors have historically been associated with severe negative immune responses and like LNPs, cannot be delivered orally. We believe LNCs provide a differentiated alternative to LNP and vector delivery. LNCs can effectively deliver molecules through both endocytosis and membrane fusion, in addition to having great flexibility with the desired route of administration. Because of their unique structure and delivery mechanisms, LNC formulations are not immunogenic and allow for safe, repeated administration, both significant drawbacks that have been observed with vectors and LNPs.

The structure of an LNC is also highly stable, protecting the payload both prior to and following administration into the body. This stability obviates the need for the extreme cold chain storage temperatures otherwise required for maintaining the integrity of LNPs. Furthermore, since LNC payloads are protected outside of cells and within the digestive tract, LNC formulations enable oral and even intranasal delivery in addition to the more standard IV administration. Because of their unique and proprietary composition, LNC enters cells in unique ways. And once they get inside of a cell, they release their cargo, thanks to the much lower calcium concentrations.

Clinical and preclinical studies have demonstrated successful delivery of LNCs and a therapeutic cargo to professional phagocytes, including macrophages and directly to sites of infection, inflammation and tumors. Each of these sorts of target cells have either exposed phosphatidylserine, which enable cellular fusion or specific phosphatidylserine receptors, which facilitate receptor-mediated cellular uptake. This specific cellular targeted, coupled with the potential to deliver a broad range of therapeutic agents, including small molecules, vaccines, peptides and proteins as well as nucleic acid polymers provide a broader way of potential targets and modalities from which to create a broad pipeline of internal product candidates and partnerships.

Alongside our internal discovery work focused on messenger RNA, DNA and antisense oligonucleotides, we remain in advanced discussions with leading biopharmaceutical companies in the nucleic acid space. We believe that a true partnership in this area will further validate our LNC platform while increasing third-party interest in additional applications of our technology. Unlike numerous other companies in the LNP area, Matinas is the only company working with LNCs, and we have built a significant intellectual property portfolio, combined with decades of knowhow to protect what we believe can become the next-generation platform in intracellular delivery. We remain very excited about our work with small molecules, but we are intent on taking our technology more broadly into nucleic acids and look forward to important and potentially significant updates on these efforts during 2022.

I will now turn the call over to our CFO, Keith Kucinski, who will discuss our financial results.

Thanks, Jerry, and good morning, everyone. Today, the company reported a net loss attributable to common shareholders of approximately $6.7 million or $0.03 per basic and diluted share for the fourth quarter of 2021 compared to a net loss attributable to common shareholders of $6.6 million or a net loss of $0.03 per share basic and diluted for the same period in 2020. For full year 2021, the company reported a net loss attributable to common shareholders of approximately $23.7 million or $0.11 per basic and diluted share compared to a net loss attributable to common shareholders of $23.2 million or a net loss of $0.12 per share basic and diluted for full year 2020.

Research and development expenses were approximately $4.2 million in the fourth quarter of 2021 compared to approximately $3.5 million in the same quarter of 2020. For full year 2021, R&D expenses were approximately $14.6 million compared to approximately $14.3 million for full year 2020. General and administrative expenses were approximately $2.5 million in the fourth quarter of 2021 compared to $3 million in the same period of 2020. For full year 2021, SG&A expenses were approximately $10.2 million compared to $10 million for full year 2020. Cash, cash equivalents and marketable securities at December 31, 2021, were approximately $49.6 million compared to $58.7 million at December 31, 2020. 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.

Thanks, Keith. In summary, we are on a strong trajectory for a highly successful year ahead. We continue to deliver highly compelling clinical data with the EnACT trial, Cohort 4 data expected early in the third quarter of 2022 and recently partnering with a global CMO to drive toward NDA readiness for MAT2203, positioning it to hopefully potentially become the leading therapy in the treatment of invasive fungal infections.

We continue to invest and expand our discovery team with active programs now in a variety of areas in the nucleic acid space. We'll have data from Genentech and from Gilead coming up in the middle of 2022 and the potential for early data from our discovery programs in messenger RNA, DNA and antisense oligonucleotides. We're intent on driving these programs forward and addressing some of the major challenge in the delivery of these therapeutics. We have real momentum going forward, near-term milestones, and we look forward to keeping everyone updated on our progress through 2022.

With that, I will turn the call over to the operator for a question-and-answer session.

(Operator Instructions) Our first question today is coming from Bert Hazlett from BTIG.

Congratulations on all the progress. So material efforts underway and obviously have been accomplished during 2021. With regard to 2022, Jerry, you made a couple of very intriguing points with regard to interest by third parties. I'm interested in the strategy in general there. The interest, I guess, is growing in 2203. Is that a candidate for licensing or partnering? Or is it more with regard to other opportunities in the platform like an antisense oligos or RNA or DNA or other different types of molecules? Just interested in the strategy more broadly with regard to Matinas.

Yes, Bert, great question, and thanks for joining this morning. I think 2203 has always been for us a foundational drug. It's clearly demonstrating the key attributes of the platform. We're getting oral bioavailability. We're keeping the patients safe and we're having success in targeting infections in hard-to-reach places in the body. The data from EnACT, those first 3 cohorts and what we're seeing in Cohort 4, do set this up to be a very successful drug. And that's attracted a lot of interest from third parties. So our strategy is to capitalize on that. We've seen deals in the anti-infective space during and just after Phase II from global partners where the increasing incidence of infections globally and the lack of investment in this space has made companies very hungry for differentiated assets. And when you're talking about 2203 with its broad spectrum nature of amphotericin B and now the opportunity to make that oral and essentially safe, you're talking about a drug that has an opportunity to treat tens of millions of patients. So we are preparing this drug because of interest that's been expressed already. We have an idea of what these companies are looking for. And for us, it's a question of timing and checking boxes. So as we think about where Matinas is today with roughly 34 employees and a focus on discovery and formulating drugs and creating drug candidates, we do believe that 2203 is a great candidate for a partnership. That doesn't mean that we would not continue to develop that drug through NDA filing and perhaps through global development as well. But the interest is real, and we think they care about things like Cohort 4 data, the Cohort 5 validation from FDA. Certainly, now that we have a global CMO, that's a big box, being able to show that you have CMC and scale up at least planned is really important. Getting that advice from EMA is also setting this up. So we think in the second half of this year, specifically off Cohort 4, that interest is going to intensify. It's already strong. It's going to intensify. And we think getting through some of these near-term milestones will also increase the value to the point where it does make sense for us to entertain that.

And I would say 2501 is in the same bucket because as you look forward with Matinas, our strategy here is we're a platform company. And we have a differentiated, unique platform, intracellular platform delivery. And if you look even today, the interest and the importance of delivery is highlighted with every day moving forward. I mean, Voyager deal with Novartis today, we take a keen interest in things like that, where companies are investing earlier and earlier in potential delivery solutions in the gene therapy and nucleic acid space. It's one of the reasons why we've invested so heavily internally in the back half of 2021 and now turning the page to 2022 in nucleic acids. And the partnership interest is real there too. So it's a combination of setting our clinical stage assets up for commercial partnerships and then expanding the utilization of the platform to the point where we can enjoy some of those more meaningful collaborations with third parties in the oligo space.

I have about 7 or 8 more, but I'm only going to ask one, and I'd love to ask about 2 questions -- 2 programs, excuse me. Could you describe a little bit more about the data that is upcoming that we can expect with regard to 2501 during the year? And then with regard to the -- remind us of the Gilead and Genentech data that we might see during the year as well.

Thanks, Bert. All right. So 2501 first. Look it's a little bit in the shadows of 2203 just because it's a little earlier. But when you have the potential for the first oral aminoglycoside, it's a big drug with a lot of interest. We actually had another great update meeting with the Cystic Fibrosis Foundation yesterday who continues to be very motivated in helping to drive the development of that drug. We're right now in a single ascending dose PK study. So we're gathering data about the safety of our drug in healthy volunteers. Enrollment is going well, and we expect to have data right in the middle of 2022. But we expect this drug to be safe. So what we're really doing now, in the background we're also doing some longer-term tox studies, which are going to set us up for a Phase II trial. We need to begin and have begun to plan what that may look like with the Cystic Fibrosis Foundation and others. But the data from the SAD is really validating that we continue to have a safe drug. I mean Amikacin is one of the most highly toxic aminoglycosides. In addition to sort of nephrotoxicity, you get ototoxicity, you can take away your hearing. And so we need to continue to demonstrate that our LNCs can eliminate that toxicity. In addition to facilitating intracellular delivery, which can target the therapy right to the lung, a lot of therapies targeting NTM and other pulmonary infections fail because they can't get any drug or they can get a limited amount of drug to the lungs. Well, we've shown the ability to get drug right to the lungs, and that's because of our mechanism of action being taken up by monocytes, maturing into macrophages, going right to the site of infection. That's been established now in multiple preclinical studies. And obviously, EnACT is another validation of that. So we're excited about 2501. The data from SAD, we believe will sort of be consistent with what we've seen with the safety of our platform. And so we're looking forward to that.

On the Genentech front, the third compound, we've done a small molecule. We've done an antisense oligonucleotide. The third compound is going to be different, and it's going to be -- we can't talk about it yet, but it's going to be in a very, very interesting area, something that we have not -- we've done some type of these molecules before, but not the specific one. So it's going to be an opportunity to expand the platform. We're waiting for the final protocol from Genentech for that. But we're excited about that because we think more so than the small molecules and oligos, this is going to allow us to put a stake in the ground, which we think will cause investors in the market, their heads will turn. And then on the Gilead front, the second in vivo study is going to start. We say shortly, I'm talking about in the next week or so. Formulations were sent down a few weeks ago. And that's important because it's going to be another COVID-19 model. It's going to give us the opportunity to show that we can knock down the inoculum there and essentially deliver a prodrug orally, which is really, really hard. Remdesivir is not an easy drug to work with. And for us, continuing to work with Gilead and the NIH is continued validation of our platform in more and more areas. So regardless of how you feel about remdesivir as a drug opportunity moving forward, this is additional data with the delivery of a prodrug and an antiviral. And with the way the world is evolving here, antiviral medications, specifically oral antiviral medications are going to become more and more important. And our unique ability to get them inside cells without any unintended immune response is a great demonstration. So -- and that's coming in the middle of 2022 as well, Bert. So 2 really good questions.

(Operator Instructions) Our next question today is coming from Mayank Mamtani from B. Riley.

This is Yuan on for Mayank. Can you share more details of the design for Cohort 5? And we want to know, will this new cohort have impact on the time line? Also can you clarify why this cohort might be required in terms of regulatory requirements? Because on one side, it's requested by FDA, but on the other side, it seems that you still need FDA input on the design?

Great, it's a good question, and I'll ask Dr. Matkovits to go into some details. So our discussions in December focused specifically on this and the opportunity and the pathway for -- to filing an NDA for step-down treatment. So there's always already been a good deal of FDA input into this idea of Cohort 5, it being satisfactory to them in qualifying for essentially a pivotal stage cohort and generating the data necessary to file an NDA. So now taking that feedback from December, our discussions in early April are really just refining the design that FDA is already comfortable with. So it's really going to be narrowly focused on the endpoint, which we've said we believe can be 30-day survival where our data is very compelling versus IV amphotericin, the non-inferiority margin and then the size of the safety database. So overall, it doesn't change our time line. CMC was always our gating item to filing an NDA. And with the expansion of the number of clinical sites from 2 to 5 in Uganda, we think we can enroll it reasonably quickly, keeping in mind that this is still a deadly invasive fungal infection. So it doesn't necessarily change our time lines too much in terms of being able to file an NDA. But we do expect that our discussion with FDA in April will be pretty narrow and focused and gaining their agreement is important, but we feel that they already have a lot of information and have already provided a lot of input. But Terri, maybe you can expand on that a little bit.

Sure. Thanks, Jerry, and you've covered it very well. So we're really very well positioned now to have a very focused discussion with the FDA. We've already crossed the major hurdles with getting their alignment that we don't need to expand the program into U.S. patients. We can focus on where we know the patients exist and where there is a high unmet need in Uganda, where we know we can enroll the trial very quickly at the same site, at the same centers that are already treating patients with our oral MAT2203. So the operational execution should be very seamless as we're really just replicating what was already demonstrated in Cohort 2. It will continue to be, we expect, an open-label design for an endpoint that we know we will win based upon, of course, the data that we've generated to date. So we're optimistic that FDA will agree with the endpoint and the statistical analysis plan that we will be submitting for their review. And really, this is just a final step in getting FDA alignment on the study that will be critical for NDA submission.

And just one follow-up here. After the April discussion, when will we hear any feedback or update on this program?

Sure. So it takes about…

Great. Yes. Go ahead, Terri.

Sorry. It takes about 30 days. Within 30 days we should receive the final minute, but we'll have an idea around the time of meeting as get their written feedback, their initial thoughts on the design. But final feedback is typically 30 days after the meeting is concluded.

And just given the way the calendar is setting up, it does look like we'll be in position to provide that substantive input during our first quarter conference call in May. So the calendar is sort of working in our favor where as the update comes in, it's sort of right in line with when we expect to inform the market about Q1 results. So it's going to line up pretty nicely. And by then, we should also be much further along with Cohort 4. And so during that May call, those would be 2 key updates from the company, both with respect to FDA and then the continued successful intervention with MAT2203 and an all-oral regimen.

Our next question today is coming from Greg Fraser from Truist.

I got on a bit late, so I apologize if this was asked already. But on 2203, for a theoretical upside scenario in terms of filing timing in which you're able to submit the NDA prior to completing Cohort 5. What do you envision potentially supporting an early submission, interim results in a certain threshold? I realize this will depend on your discussions with FDA, but I'm curious how you're thinking about an upside scenario for timing? And then just a quick one on R&D and SG&A spend. How do we think about spend in 2022? And then specifically for Cohort 5, how should we think about the cost for that cohort? And how much of that cost would you expect the NIH to cover?

Sure. So Greg, I'll take those, and thanks for the questions. So in terms of upside timing, there's 2 different variables to that, right? Because some of the upside in timing will also be FDA's willingness to allow us to file an NDA with shorter stability on registration batches. So that's already assuming that FDA is comfortable with the 6-month stability, which is there's precedent for that, but that would be sort of the first opportunity for an earlier filing. And then in terms of, because it's open label and because we can have more frequent interactions with FDA because of our regulatory status and some of the other designations that MAT2203 has. There is that opportunity to go in there. If we're seeing consistent results through, let's say, the first half to 75% and maybe an opportunity to go in, that will be one of things that we talk about with FDA, not only in April, but probably more as Cohort 5 starts to get drawn off. I still think it's optimistic to think that we'd be able to file an NDA in late 2023, primarily because of the CMC side. But if the data continue to be as compelling as they have been in Cohort 2 and now what we're seeing with Cohort 4, remember, when FDA was evaluating this drug or we were discussing the data in December. We didn't have the benefit of any of the data from Cohort 4, which is important because it eliminates that question of what impact does IV amphotericin have, for example. And in Cohort 4, you get to answer that question. And so far it's none, that all of the results we're seeing during the induction phase with MAT2203, are MAT2203 is alone. And the patients, as I mentioned during the call, those on MAT2203 are all doing well, and nearly all of them have achieved sterility. The only ones we don't know are the ones that haven't finished the induction period yet. So those will be important elements to discuss with FDA. So that's very important. So there could be an opportunity to move NDA filing up a little bit in 2023, but we have to see how those 2 key inputs sort of go over the course of this year.

In terms of the cost of Cohort 5, we believe that that will be covered by NIH. That process is already in place. Dr. Boulware is working with the NIH on that. Obviously, the NIH has been a great partner to Matinas and to this platform. And so we would expect that support to be there again. Matinas' contribution historically has been the cost around manufacturing and supply of the drug, some study monitoring and things like that. But we do believe that regardless of the ultimate size of Cohort 5 that NIH will be willing to step up. And that's a big deal for us. And so we're counting on that. Our cash flow forecast takes that into account. But we wouldn't do that unless we had a high degree of confidence. And obviously, David Boulware also has a very, very good relationship with the NIH. And so that's sort of how we're thinking about 2203.

I missed one question in there, Greg, though. Remind me of what the third point was.

Just how to think about R&D and G&A spend.

Yes. I mean, obviously, we're continuing to invest in the platform, but we're doing so in a disciplined way. Adding headcount has increased sort of the R&D spend modestly over the period. We don't expect huge increases and any increases or any additional investment, we're also, we believe, going to have the opportunity to offset those with some non-dilutive capital. So we're not evaluating any sort of capital raise at the moment. We're generally comfortable with our cash position, taking into account some of the catalysts and milestones we have ahead. But for 2022, it's going to look consistent with what we've spent, I would say, over the last 6 months internally here as we've shifted away from LYPDISO and that would continue sort of on a straight line through 2023 as well.

We've reached the end of our question-and-answer session. I'd like to turn the floor back over to management for any further or closing comments.

Great. Thanks, Kevin, and thank you all for joining us today. We appreciate your continued interest in Matinas, and the team here really looks forward to providing with updates on our future progress. Have a great day.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.