Good morning, ladies and gentlemen, and welcome to the NRx Pharmaceuticals Discusses FDA First Cycle Review conference call. At this time, all lines are in a listen-only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. I would now like to turn the conference call over to Brian Korb from Astr Partners. Please go ahead.
Thank you, operator. Before we begin, I'd like to remind everyone that certain statements made during today's call may be considered forward-looking statements within the meaning of applicable securities laws. These statements are based on management's current expectations and assumptions that are subject to risks, uncertainties, and other factors that could cause actual results to differ materially from these expressed or implied. Please refer to the company's SEC filings and today's press release for a discussion of these risks. NRx Pharmaceuticals undertakes no obligation to update any forward-looking statements except as required by law. Joining us today are Dr. Jonathan Javitt, Founder, Chairman, and Chief Executive Officer of NRx Pharmaceuticals, and Glenn Tyson, Chief Commercial Officer. Dr. Javitt will provide an overview of the company's recent developments and strategic priorities, followed by remarks from Glenn on commercialization activities and market readiness initiatives.
Following their prepared remarks, we'll open the call for questions. With that, it is my pleasure to turn the call over to Dr. Jonathan Javitt. Jonathan, please go ahead.
Thank you, Brian. Good morning, everyone. It's a privilege to meet with you and update you on the progress of our Abbreviated New Drug Application, otherwise known as an ANDA, for preservative-free ketamine. As you know from our press release, we've completed our first cycle review with FDA, and we're delighted to share with you that, to the best of our knowledge, we have only one matter to clarify with FDA prior to approval. The agency has advised us that there are no major deficiencies related to our drug, to its ingredients, to its manufacture, to chemical manufacturing controls, to labeling, or any related matter connected to the drug itself. The sole remaining item is a concern raised by a reviewer that the luer lock tip might deform in use and might not mate properly to the syringe.
Our vial is different from the glass vials that people are used to in that you do not have to open the top, put a syringe on a needle, push the needle through the stopper, draw up the medicine, remove the needle from the syringe, dispose of the needle, and finally administer the medicine to a patient. Instead, all you have to do is twist off the plastic cap of the vial, connect the luer lock syringe to the neck of the vial, draw up the medicine, and administer it with no chance of a needlestick injury or sharps waste along the way. The ANDA contains documentation that this vial has now been used in three currently FDA-approved products that have collectively shipped about 11.9 million doses in the last 12 months with no complaints, no returns, no adverse events, and no recalls.
Moreover, the ANDA contained testing data documenting in-process testing of 500 vials per manufacturing lot for each of our seven lots, with no malfunctions observed in any of the 3,500 articles that were tested. The vial is manufactured under full design controls as specified in Code of Federal Regulations Part 820.3, which includes strict adherence to the ANSI standards underlying luer locks and precise testing procedures for the twist-off force that is required to open our vial. We actually measure it down to newton centimeters. We have a special testing rig that does this precisely and mechanically. FDA has inspected this vial component on multiple occasions during its plant inspections at our manufacturer for the other products.
In a meeting on Thursday, the FDA recognized the extensive measures we took to comply with medical device law related to the luer lock tip and the documentation of this both in the ANDA and on file at our manufacturer, where it was already inspected. Accordingly, FDA asked us simply to submit an attestation from the manufacturer that our vial is manufactured on the same manufacturing lines using the same materials and methods of the three currently approved products. This attestation is being submitted today. We believe the request we received is consistent with a final verification step rather than a request to generate new technical data. Because the requested information was already available from our manufacturing partner, we are able to respond immediately. We are delighted by this outcome, and we believe it significantly de-risks the likelihood of a near-term approval of our ANDA.
As a result, we are planning to increase our manufacturing orders substantially beyond the first one million units that we already announced to five million units of launch stock. In today's regulatory environment, only 14%-18% of ANDA products receive a clean approval in the first review cycle. To have emerged with only one item that was classified as major, where we believe we have arrived at a rapid path to resolution with FDA, is way ahead of the curve from our perspective. Importantly, this was not a review cycle that identified new studies, additional manufacturing work, labeling revisions, or changes to our commercial plans. Based on the feedback received, we continue to move forward with launch preparation supply chain expansion, distributor onboarding, and the commercial infrastructure necessary to support market entry once the review process is complete. As you know, ketamine is on the FDA drug shortage list.
It's been identified as a strategic drug product by the military and the VA. Hence, approving a U.S. manufactured source of ketamine at a time when hospitals and clinics are forced to buy non-FDA approved compounded ketamine from local pharmacies is a priority that goes all the way to senior levels of government. Our focus now is straightforward. We aim to complete the regulatory process, continue scaling inventory, and to be prepared to launch into a market where reliable domestic supply remains critically important. With the regulatory review substantially advanced and our commercial preparations accelerating, we believe NRx is well positioned to create meaningful shareholder value through disciplined execution and a clear path toward commercialization.
Last quarter, we told you that we had recruited Glenn Tyson to serve as our Chief Commercial Officer. I've asked Glenn to offer some thoughts on our commercialization plans, and then we'll take your questions. Glenn?
Thank you, Jonathan, and good morning to you all. Happy to have this opportunity to meet you and give you an overview of our commercialization plans underway. As you're aware, this ANDA is the first key step in our progress toward commercialization of a portfolio of assets that we believe will provide new hope for people suffering with serious mental illness. NRx is not relying on a single product strategy to carry the story. Instead, we are deploying a staged commercialization model that starts with the ANDA and builds towards the launches of premium reimbursed branded therapies, NRX-100 and NRX-101. If approved, these two products could provide much needed options for people suffering with severe depression and suicidality. The interventional psychiatry market for ketamine, esketamine combined is growing rapidly and will likely exceed $3 billion in 2027.
We're already in the planning stages of a commercial model for NRX-100 that we believe will achieve broad market access, significant penetration in the growing interventional psychiatry space, and substantial revenue. What we can see is that the insurance reimbursed market is what's driving the profitability in this sector, and NRx looks to benefit from this with our portfolio of strategic assets. This launch sequencing allows NRx to generate potentially significant early cash flow from the ANDA while constructing a much more robust long-term market position with multiple proprietary assets. This first launch gives us the opportunity to set up a seamless distribution network that will both ensure we can meet market demand for ketamine and help solve the problem of the ketamine drug shortage in the U.S.
The ANDA, while launching into a generic market, has differentiating characteristics that when paired with an optimal distribution plan, we believe will lead to substantial market penetration. As a reminder, our ANDA product comes in a luer lock vial, as Jonathan just outlined, and this allows for needleless draws. It is free of all preservatives, including benzethonium chloride, which is found in all other ketamine products currently on the market. Perhaps most importantly, we have consistent, reliable supply that is made in the USA. Taken as a whole, this opportunity can expand access to ketamine in the U.S. for patients in need. Today, ketamine remains an important tool as a non-opioid anesthetic for many common surgical procedures, as well as having a place in emergency medicine, pain management, and within interventional psychiatry.
Our distribution plan takes into account all the various customer types and channels, and we believe our launch dosage form of 50 mg, which is 10 mg per milliliter in a 5 ml vial, will be seen as an important product that can reliably meet medical needs across a broad spectrum of sites and uses. At NRx, we are serious about addressing the issue of drug shortages, and with an optimized manufacturing process and supply chain reliability, we can produce new batches very quickly and cover any market fluctuations created by other manufacturers' inability to guarantee consistent supply. We are pairing this with a streamlined and highly compliant ordering system that verifies the necessary licensures of all customers and then delivers product confidently.
At this time, the commercial team is setting up all the necessary distributor contracts and preparing all the forms and electronic systems for accurate and timely government reporting, as well as finalizing implementation of financial reporting systems. We are also building required company infrastructure by setting up pharmacovigilance and medical information functions, as well as other systems to capture any customer issues. Because of what we learned in recent market research with purchasers in all channels, we have increased our plans for initial commercial supply manufacturing from the one million vials already in plan to four to five million vials to meet initial launch demand. We would not be making this level of inventory commitment unless we had high conviction in the opportunity, the market demand, and our readiness to execute.
Once the ANDA is approved and all labeling is finalized, we will be ready to launch and confident in our ability to deliver meaningful results for shareholders. That concludes my prepared remarks. I will be available to answer questions upon the conclusion of this discussion. With that, I will turn the call back over to Jonathan.
Thank you. Brian, would you like to introduce our questions?
Yep. Sounds good. Thank you, operator. Please go ahead. Appreciate it.
Yes. Thank you, ladies and gentlemen. Should you wish to ask a question, you may press star one on your telephone keypad. Once again, that is star one should you wish to ask a question. Your first question is from Elemer Piros from Lucid Capital Markets. Your line is now open.
Yes. Good morning, everyone. Jonathan or Glenn, would you please explain how you were able to overcome what others are struggling with in terms of shortage and secure the U.S. supply of the drug is question one. Question two, if you could describe the economic benefit to NRx, specifically for this first five million vial opportunity.
Well, thank you, Elemer. When you say, how are we able to overcome a shortage? The only way to overcome a shortage is to manufacture into that shortage. Now, I think there are a couple of reasons why we are in a position to do that. Every vial of ketamine today is sold in a glass vial with a rubber stopper. Pharmaceutical glass is increasingly expensive and increasingly in short supply. More importantly, a glass bottling line can generally manufacture about 10,000 units in a manufacturing run. A blow-fill-seal bottling line, where you're fabricating a vial from a couple of pellets of plastic, can manufacture one million units in the same amount of time with the same workforce, or less.
Because literally the machines we're using take pellets of plastic, melt them into a little puddle. That puddle is infused with air to form the shape of a vial. That vial is automatically filled with medicine. The machine seals the vial, puts a label on the vial, puts a wrapper on the vial, puts it into a box, and puts it onto a pallet without a single human being touching that process. That's very different from an old-fashioned glass bottling line.
I see. Thank you.
Almost unlimited manufacturing capacity. At least unlimited compared to the ketamine market today. We don't need to buy pharmaceutical glass in order to satisfy that capacity.
I see. So it was mostly, or it is not necessarily drug related, but the entire process related and including the glass vials that leads to the shortage.
Well, correct. If what you are asking is whether there is a shortage of ketamine API, ketamine pharmaceutical ingredient, to our knowledge, there is not, and we have very significant amounts of ketamine API in the warehouse ready to go. Really the shortage is the capacity of the current manufacturing lines. And one of the problems is ketamine is a fairly well-known drug. Its price is not exorbitantly high. So if you have got a choice between devoting a manufacturing line to a biologic that could sell for thousands of dollars per vial
Or an old sterile generic injectable product, the expensive new drugs are going to capture the manufacturing capacity out there. The other thing to recognize is that much of the ketamine supply today is coming from overseas. Overseas supply lines have been significantly disrupted, as anybody who reads the news knows. So there is a real need for a high-capacity supply that is manufactured in the United States, and that is what we aim to do.
Yeah. To part two of the question, or second question, Jonathan, if you could explain what you expect on?
Well, at some point we may give more guidance about the margins that we expect to achieve with this product. But I think just in terms of common sense, people can recognize that a couple of pellets of plastic is a whole lot less expensive than a glass vial, a rubber stopper, a metal crimp, and the machinery that's required to put all that together. Recognize that that glass itself is not problem-free. Keeping lint out of glass, washing glass, is an ongoing challenge for people who are in that sterile injectables business. So we expect that our unit margins will be significantly higher than the unit margins of people who are bottling in glass, and we'll give some more precise guidance about that at the right time.
Yeah. Do you think you could maybe elaborate on what sort of premium you hope to get for the preservative-free version of ketamine?
I think it's premature to talk about what sort of premium we might get. Quite frankly, if at the outset, the preservative-free advantages simply capture additional market share, that'll be a major win. A premium, that'll be a win on top of it.
Okay. Yep. Thank you so much. I'll get back to the queue.
Thank you. Your next question is from Patrick Trucchio from H.C. Wainwright. Your line is now open.
Hi, it's Erica. I'm in for Patrick. Thank you so much for taking the question. I guess, has a new GDUFA date been assigned for the amended submission, and is it going to be treated as a minor amendment or a major amendment? What does the shortest possible review cycle really mean? Then separately, what specifically changed in the KETALAR reference with the drug label? Thank you.
A new GDUFA date hasn't been assigned, therefore, we can't answer the rest of the question. FDA's posture in the call was extremely collaborative. Not only was the Office of Generic Drugs on the call, but so was the leadership of FDA’s Center for Drug Evaluation and Research, otherwise known as CDER. You know, the FDA recognizes that this is a strategic drug that's in drug shortage, where the supply chain is primarily an overseas supply chain, and there's a very high priority that goes all the way to the Secretary of Health and beyond to reshore the manufacture of strategic drugs to the United States. With regard to the specific change in the RLD, I don't have that information for you today. We can certainly get it out there. But it was not a significant change. People make labeling changes all the time in old drugs.
And in this case, a small change was made after we had filed the ANDA, so we have already updated the ANDA to incorporate that change. We got that filed last night.
Thank you so much. Have you submitted the manufacturer certifications yet? If not, when do you expect to submit those?
This is the manufacturer that has been repeatedly inspected by FDA. They are in VAI status. I think we are fine on that front.
Thank you so much.
Thank you. Your next question is from Thomas Shrader from U.S. Bank. Your line is now open.
Good morning. Thanks for taking the questions. Can you give us a little update on how much preservative-free text you will be able to get into the label? Will you be able to give any sort of comparative data or things like that? Glenn, I enjoyed your comments. It sounds like you know what you are doing. I am curious if you can give us some background on other drugs that have launched into this sort of filling shortage market and what you are looking at as a stalking horse for how to pull this off. Jonathan, if you could, I would love you to give us an update on the BLA timeline. That is your next big catalyst, so I appreciate you are focused on today, but as much detail as you could give us would be great. Thank you.
Tom, with regard to what we expect to see in the label, I think the fact that it is preservative-free hopefully will be noted in the label. It may simply be noted by the fact that there is no preservative listed, in which case we will be free to tell the market that it is preservative-free. I would not expect to see comparative data in an ANDA product because typically, ANDA products are labeled with the label of the reference listed drug. That would be a little bit new to say, well, let us put information in the label about toxicity associated with benzethonium chloride. On the other hand, in our outreach to the market, we are certainly free to identify the toxicities associated with benzethonium chloride.
In fact, the toxicology report is posted by the FDA as part of our open docket, where we have requested a citizen petition to remove toxic preservatives from injectable drugs.
Got it.
Yeah. For the most part, labels are written in six-point type, and that is typically not where people look for that kind of information. Before we go to Glenn, what was the second question you had for me, Tom?
Oh, it was at the end, an update on the BLA, what you can tell us about where you are.
Well, BLA is for a biological.
I'm sorry. NDA. I misspoke. NDA. Sorry about that. Your NDA. Sorry.
Yeah, we were poised to get that submitted in June, and as we started to run into this question on the luer lock and provide FDA with information on that, we wanted to get this resolved because that same vial applies to both products. Now that we've cleared this, we're going to turn our attention back to the NDA. We've, in the background, been talking with FDA about how they'll interpret the real-world evidence. As you've seen, there's both a presidential executive order and there's direct language from the Congressional Appropriations Committee that funds the FDA, guiding the FDA to use the 65,000 patients of real-world evidence. We've presented this evidence at a clinical meeting, so it's out there.
The evidence not only demonstrates the significant efficacy of ketamine in resolving depression suicidality, but demonstrates that the effect is larger and more rapid than the effect seen with intranasal esketamine. So, we've consistently said that we think the NDA is going to get dealt with over the next 12 months. That was 12 months from June, and quite frankly, I think that having dealt with this packaging item ahead of time keeps us within that timeline.
Thank you, Jonathan. Yes. So, to your other questions, just a couple of things. First, I'll say hat in the carton packaging that the luer lock vial will be contained in, there is statements about it being preservative-free. I'm not sure how significant it will be in the actual label, but certainly in the packaging it will be noted, and we will ensure that all of our distributors are aware of the differences of the product and the potential benefits here. As part of our market preparation, as you can imagine, we've done a fair amount of market research that's still underway, and we're interviewing purchasers at various levels within hospital systems, within specialty accounts, within interventional psychiatry, and various clinics. We're testing the profile to understand what will make a difference. What I can tell you is that the preservative-free comments are certainly things that they're concerned about.
I think the awareness of benzethonium chloride and any challenge that may present to their patients is not well-known to them, but they are happy to hear about the preservative-free nature of our product. Secondly, the fact that we are talking about consistent supply is something that's very important to them. It's a very sensitive issue, and all customers in ordering are having to toggle between manufacturers and compounding pharmacies, which creates challenges in terms of their consistent supply and their feeling about having a safety net of supply that they can count on. So that's very important to them, and we're hearing that pretty consistently across the board.
I think, just in final, I would say it's uncharacteristic as a market launch into a supply shortage. What we're trying to understand is really what it means to our customers and how we can talk to them, ensure that they are very clear on the benefits of the product that we have, and how do we move them to an ordering system that is very simple and that is reliable. So that's really where we are with trying to penetrate this market and meet the drug shortage, and that's meeting with the very positive comments from our customers that we're speaking with.
If I can squeeze in one quick follow-up. How many customers do you think you really need to hit to get, I don't know, a significant fraction of the market? How lumpy is the target market?
That's a really good question. It's a market that's segmented into the purchasers are on-label use in hospitals, hospital systems, et cetera. Then you have the interventional psychiatry space. There's about 8,000 interventional psychiatrists in the U.S. But it's very highly concentrated in terms of the number of customers that are purchasing. And we believe there's probably about 2,500 that are purchasing the majority of the ketamine here. So maybe that's not an exact perfect Pareto Principle, 80/20 rule, but it's pretty close.
Perfect. Great. Thank you for all the details.
Thank you.
Thank you. Once again, that is star one should you wish to ask a question. And your next question is from Ed Woo from Ascendiant Capital. Your line is now open.
Yeah. Congratulations on all the progress. Assuming that you can get approval tomorrow, or how quickly after approval will you be able to start selling product?
We have.
Ed, I think that's a great question. As you know, we guided at the end of the quarter that we had initiated manufacturing of a million units of launch stock, and we just told you today that we're increasing that to five million based on the funding that we raised and based on the market forecasts that we're seeing. Our anticipation is that we should be able to start shipping within a couple of days of FDA approval.
Great. That's great to hear. Thank you for answering my questions, and I wish you guys good luck. Thank you.
Thank you.
Thank you. There are no further questions at this time. I will now hand the call back over to your hosts for the closing remarks.
Thank you very much for joining us, Jonathan. I do not know if you have any final comment.
No. All we can really do at this point is thank our shareholders, particularly thank the people who stepped in on our recent public offering to provide us with the resources to be ready to launch this drug when it is approved. We look forward to continuing to bring you news. We will see you on the earnings call in about a week. Thank you for joining us.
Thank you, ladies and gentlemen. That concludes our conference call for today. Thank you all for joining. You may now disconnect your lines.