Okay. Good morning, everyone. I'm Paul Choi, and I come from the small and mid-cap biotechnology sector here at Goldman Sachs. Before we begin, we'd like to make certain disclosures regarding the companies that are being discussed here today. Completely regarding us investment relationships, compensation, 1% or more. Closures are available read aloud during any session on your... However, they are available on our research portal for your information. Goldman Sachs only undertakes this under the assumption that any third-party speaker here today will not provide any confidential or material non-public information. Additionally, the views expressed by third parties do not necessarily reflect those of Goldman Sachs. With that, we'll continue. It's my pleasure to welcome Phathom Pharmaceuticals here. We're joined by the senior management team.
Starting on my left is Martin, then to my immediate right, at the far end, sorry, we have Azmi, Molly, and Terrie. What we'll do is let Terrie kick it off with some Q&A or some opening remarks, then we'll get into Q&A.
Buddy, thanks for inviting us to the conference, Paul. Phathom is a company that's focused on developing and potentially commercializing a potassium-competitive acid blocker for acid-related disorders. We are very far progressed in the development of this compound, which represents the first PCAB to enter the marketplace here in the U.S., Europe, and Canada. We have completed three phase III clinical programs, one in the eradication of H. pylori, the second in erosive GERD, and the third in non-erosive GERD. The first two clinical trials in HP and EE, both showed superiority versus the standard of care, and we anticipate launching both of those indications by Q4. We did receive two CRLs related to trace levels of nitrosamine, which in consultation with the FDA, we worked through a number of mitigation efforts.
One of those being a reformulation, a minor reformulation of the tablets. We began manufacturing in December and agreed with the FDA that we would resubmit the NDAs, which we did two weeks ago. We're absolutely thrilled that we're back on track, and very close to commercialization. If successful, this will represent the first new innovation into this category with a new mechanism in more than 20 years, and really is a meet the needs of a very large market. Population is about 22 million patients that suffer from GERD, that have really no other options in the standard of care, which is PPI. Very excited to be back on track and to be here to talk with you.
Great. Thank you, Terrie, and congratulations on the, on the NDA. For investors who may not be familiar and may not have the context with the background prior to your resubmission here, can you maybe briefly summarize the issue that originally, you know, led to Phathom receiving the CRL and back in February?
Yeah. When we were running confirmatory testing on stability of our product before the launch of H. pylori, we found trace levels of N-nitroso-vonoprazan. None of the other nitrosamines were found. However, we found trace levels of N-nitroso-vonoprazan that rendered the product not being stable at the end of its shelf life. Since that time, that was around the August of 2022. Since that time, we worked very closely with the FDA, first to define methodology and validate the methodology of testing, but also to define the upper limit under which we need to stay during the shelf life. Also in parallel, we ran experiments, mitigation experiments, to find a path to reduce and control the nitrosamine levels. Which we have achieved all of that by December of 2022.
Based on this, we start manufacturing using a minor reformulation, and we start generating stability data. We met with the FDA in March of this year, and during that meeting, we reached an agreement to resubmit the NDA with three months data, to be supplemented by the six-month stability data, to be supplemented by the six-month data during the review, which we have done, and now we're in the process of collecting the additional three months data to submit to the FDA shortly.
Just for context, there is existing guidance on the issue of nitrosamines from the FDA, in this case, this was a novel nitrosamine that was discovered, correct?
Correct. The guidance covers six or seven nitrosamines, which we don't have any. However, what we found is something unique to vonoprazan, which is N-nitroso-vonoprazan. Other products like Januvia, for instance, have similar nitrosamine drug substance related related impurities. That's why we had to define the limit de novo, and that's what we, what we.
This is a type of problem that, a phenotype, if you will, that is known to the FDA, but in this case, this was in sort of a new quote-unquote variant of nitrosamine that was discovered here?
Correct.
Yeah. Great. Maybe, you could elaborate a little bit more on the changes you made. You mentioned the reformulation and, you know, how does this compare to the Takeda version of Takecab that's currently commercially available.
Yeah
on the Japanese market?
We're not disclosing the exact reformulation elements that we've done because of potential IP paths here. The formulation is essentially similar to what Takeda formulation is, however, the supply chain is different. We cannot comment, and we don't have exposure to what Takeda is doing specifically on the product that's specific to them. In our case, we believe the impurity is driven by nitrites in the excipients or potentially environment interacting with the secondary amine that is in the molecule. Our aim was from the mitigation, is to limit the interaction between the nitrites and the secondary amine, but also limit for any interaction, limit the growth of that N-nitroso-vonoprazan, which based on our data to date, we have successfully done so.
Okay, great. You've disclosed as part of the NDA submission process, that you now already have three-month stability data in hand, and there's a plan to submit additional follow-up or six-month stability data as part of your review process. Can you maybe remind us what, you know, in terms of like, process and methods, the stability data testing entails and under, sort of what conditions you are gathering data?
Sure. The data we collected is based on standard ICH stability guidelines, which is under long-term stability condition, which is the 25 degrees, 60% relative humidity. The accelerated stability conditions, which are 40 degrees centigrade and 75% relative humidity. For those, we had multiple configuration presentation for the products, for both the 10 and 20 milligram, in bottle packaging as well as in blisters, and we collected data at one month, two months, three months. When you add all of this together, we have many data points over the three months, and those data points all confirmed that we have very good control and ability to manage, repeatedly so, the levels of nitrosamine, nitrosamines, well below the limit that we have set for us.
In addition, we also collected stability data across the board to confirm that the minor reformulation did not affect any of the other stability parameters, which also was confirmed. We took all of the data elements, and we modeled them as well, using models that the FDA likes to see, and that projected our shelf life to comfortably meet the 24 months that we are stating.
Great. you mentioned your modeling supports a potential 24-month shelf life here, and from a commercial perspective, you know, the for instance, like H. pylori is a relatively short duration treatment. EoE could be made somewhat longer, but I guess, how important is that for you from a, from a commercial perspective?
I'll speak from stability and then. You know, it's really from a manufacturing perspective, it's to be optimal in managing the supply chain and distribution. It's not as much the clinical element, but that optimization of the supply chain and, you know, Martin maybe can comment from his.
Yeah, I think it's very manageable in terms of, you know, managing the supply chain, as Azmi said. It's also a chronic medicine, so I think, you know, people are gonna be getting... It's not gonna be sitting on the shelves waiting for the next acute therapy to happen.
Okay, great. With regard to the NDA, maybe for Terrie, you said you anticipate this will be a Class two resubmission, you know, pending the FDA's decision on that with a six-month review. Apart from the six-month stability data that we've been discussing, you know, what else do you anticipate in terms of potential data requests here, and what form could these data requests potentially take here?
Sure. We were in this resubmission, we were addressing the issues that are identified in the CRL, with well, two CRLs, one for HP and one for the erosive GERD application, both addressing the nitrosamine issue only. That's the sole issue relating to these reviews that remains. The remainder of the files have been completed, including the label, so we don't anticipate any additional requests. We will, as part of the standard resubmission, provide a safety update, but there is nothing within, you know, that evaluation that is outside of the information that we've provided before, just a regular safety update. We don't anticipate any additional requests during the process.
That's an interesting point you bring up, but just on terms of the safety update, Terrie, can you maybe just remind us where patients are in terms of a potential follow-up and duration of therapy from your various clinical trials?
Yeah. From the Japanese data, there's a study called VIVID, where they've been following patients for five years. We'll incorporate an updated package to include that safety data within the submission.
Okay, great. I know it's been relatively short time, but since your resubmission, can you comment on any FDA feedback or interactions that you've had since then? Yeah, maybe just to update your thinking on sort of, you know, how are you thinking about claims and data that you will be seeking for the EE indication?
I can cover that. The key communication we received from the FDA is that they acknowledged the receipt of the resubmission, and they assigned a target due date of November 17th. That's good. That's what we expected. Class two, six months review, that's all in line with our expectations. As for the remainder of the review, we were at a very good place when we received the CRL for the sole issue of N-nitroso-vonoprazan. Everything was really in a late stage of review. We don't anticipate any re-review, so to speak, of that material.
The label we are seeking is a label that give us the basic indication, which is that vonoprazan is approved for the treatment of healing and maintenance of healing erosive esophagitis with symptom control, heartburn symptom relief. In addition, our objective is to have superiority claims for the two-week healing for the moderate to severe patients, but also for the maintenance of healing at the six months for all patients and moderate to severe patients as well. We're on a very good path to achieve those claims. If that is met, vonoprazan will be the first P-CAB to have such superiority claims in the market.
That's great. Maybe turn to Martin in terms of what, as Azmi just mentioned, with regard to specific label claims and superiority on the two-month, two-week treatment and the maintenance period as well. How does that figure into, I guess, your commercial positioning of vonoprazan here? How important are those specific label claims in terms of fostering adoption for the EE indication?
I guess in terms of... I'll take two parts of positioning. First one is, I'll say, place in therapy. While our label allows for first-line use, I think definitely, and our position with payers, we anticipate to be one step through a PPI, which we're totally comfortable with. There's 22 million active patients in the market, meaning diagnosed and treated, and the only place they've had to go for 30 years is through a PPI. The majority of the market has met that criteria. That would be the positioning in place. I think what will make physicians move to it quickly, and we get this feedback from them, is the fact that we have superiority versus standard of care or the PPI, and that's the first time that's ever happened.
Having the superiority in the label allows us to make very strong claims. After we've sent claims down to OPDP, which is a division of the FDA that reviews your claims prior to approval. When we got the H. pylori approval, we sent down. We got back from the FDA clearance to make statements such as, "Rapid, potent, and durable, more than two times effective, superiority versus lansoprazole PPI." We have really strong messages from a positioning standpoint, and we believe we'll have really good placement in terms of positioning and therapy.
Okay, great. In addition to that, could you maybe elaborate, Martin, on where you are with regard to your commercial preparations? You're looking, you know, a few quarters away for a four-quarter launch here.
Okay.
Can you maybe just, you know, start on, start on that and, you know, maybe just elaborate where you are with regard to infrastructure build-out, starting with that, and then, maybe get a little bit more into the payer discussions.
Okay. We're actually, we're in a good, and I'll say comfortable place because our pause began when we got the news from the FDA. We were several weeks away from launch. We continued many of our activities. The medical science liaisons and the MSLs have been in place for a number of years, actually. They've been interacting with the academic community, answering questions, you know, sharing information regarding Voquezna. We've had presence at meetings such as Digestive Disease Week, and that continues through. We haven't stopped our presence. I think what made it unique in a very positive way, we had identified our sales force hiring, but we had not made offers yet, so we didn't have to carry those costs through the pause.
We can now go back to those pool of people, and those are, many of those people, or most of those people, were those that we sought out. They weren't in the market looking for a position, so we can go back to them. We'll start recruiting the sales force over the summer. We'll have them begin upon launch, and then, while they're coming on board and training, we'll start out of the gate with a digital launch, virtual launch to physicians, to the targets. Our goal is to have 300-330 sales representatives, and they'll call on roughly 49,000 high-volume, PPI high-volume, primary care and gastroenterologists. As you can imagine, gastroenterologists are kind of at the top of that pyramid.
That's where it stands with the sales force and then a virtual launch right away for a couple of weeks. From a payer perspective, we've continued dialogue with payers. We have account people who are on board. A matter of fact, you know, one of their successes to date is, since we had approval for H. pylori, we currently have 60% commercial coverage for the H. pylori packs, and given the fact that we don't have a product on the market, is quite unique and really positive, and it sends a signal that, you know, of that opportunity I was speaking to earlier. Everything's a go. We're working with the payers. We'll start recruiting the sales force. All the communication with physicians has continued, and we'll be ready to go upon approval.
Great. Could you maybe elaborate a little bit more on the payer work, particularly with regard to, you mentioned your base cases, assuming one step at it, but how do you, like, plan to anticipate helping doctors with, you know, in the case that, you know, there's payer challenges, anything, you know, maybe like a PA should come up or something like that? How do you think about facilitating the prescribing experience for physicians here?
I think I'll take the first part. You know, the situation or the strategy is, and we've seen it now proven with H. pylori, is we have superiority with erosive esophagitis as well. That superiority gives us, I'll say, the right to have the conversation. When you look at our pricing, which is a branded premium price for H. pylori, we envision a price of $17-$22 per tablet, when we have approval for GERD. That branded premium price with superiority to justify that, and that ability to contract with rebates, we believe, will get us that position. It comes down to the physician writing the prescription.
If in fact, our base case plays out, which we have every reason to believe that it will, one step through a PPI, that's typically going to be identified through two ways. At the pharmacy, 'cause they can pick that up in a nanosecond, and they'll come to you and say, "Here's your script." Or they'll say, "Hey, listen, you haven't stepped through a PPI." That would be one way, but we think the majority of the patients will have stepped through a PPI. When the doctor prescribes, everything's electronic now, there could be a pop-up and say, "Has that patient been on a PPI?" That PPI experienced patient then would automatically go through.
We'll make sure we're really transparent with physicians as to what to expect, when they write a prescription, because what we wanna do is minimize any work for them. We're not anticipating a prior authorization, paperwork, things going back and forth with the payer. That is not what we're anticipating.
Okay, great. Maybe both for you, Martin, and for Azmi. It's been a little while, and you spoke to us a little bit about your MSLs, like going out in the field and speaking to physicians, but it's been a little while since the PHALCON data were initially top-lined and presented and so forth. You know, what is sort of the, you know, muscle memory in the prescriber community, or how would you characterize it, the awareness of the PHALCON data at this point?
Yeah, I'll start and then pass to Martin. It's actually very high. you know, We are very active in publications. We're very active through the MSLs and in communication with physicians, opinion leaders. We are designing clinical trials as well, for, you know, EE as well as on-demand. We're in discussion with physicians and sites and clinical leaders on all these elements. DDW was really significant for us. Actually, the key question that we've been getting is, when Voquezna going on the market. It's that sense of, you know, wanting to use the product is very high. Our call-in center actually get calls about availability of the product, from physicians and patients as well. There's a very strong anticipation that we're welcome, obviously. Martin, your perspective.
Yeah, I think on the primary care side, if you were asked, physicians, they'd say, "Well, I'm aware, I'm aware something's coming." When you when you raise it to a gastroenterologist, they know that Voquezna is coming. They're familiar at a high level with the data. They know that it's a different mechanism of action, which is attractive, and they know that it's been compared to a PPI. That's without even sharing any information with them. Given the fact that you know, that we haven't launched yet, that's a really high awareness amongst gastroenterologists. When you then show them the data, their intent to prescribe is really high. A matter of fact, when we bring the profile to physicians, and it's just, it's just data. There's no headlines, you know, there's no powerful messages, just the data.
They allocate about 42% of their patients that they anticipate to put on Voquezna. I go back to, again, the fact that there's been nothing for them, no changes for them in the past 30 years. I think the awareness is there for us to jump springboard for us to get started from.
Great. maybe just as a refresher, in terms of market framework, you know, how much of the current EE market is sort of GI specialists in terms of prescribing behavior on PPIs relative to primary care physicians?
You know what? It's, it's evenly distributed. If you think of either as a pyramid or if you're familiar with deciling that the industry does, when you take a look at your decile nine and 10, it's mostly gastroenterologists. Primary care enters at nine, and then at eight, it tips. That's for a couple of reasons, is the majority of erosive esophagitis patients, while they might get their final diagnosis with a gastroenterologist, they're sent back to primary care, and that primary care is adjusting therapy, they're the long-term physician. They actually have patients who are coded for erosive esophagitis and making treatment decisions. That's where that 49,000 physicians comes to be.
Great. One of the things you guys have been doing, maybe for you, Terrie, is a patient access program, you know, post your clinical trials and things along those lines. Can you maybe comment on how that's going, and just how that's sort of factored into thinking about your discussions of pivoting patients onto commercial?
The patient access in terms of.
Yep. You mean like, when the patient gets there, like copay?
Yes.
Support services.
Yes, exactly.
Yeah.
Yeah. You want me to take that, Terrie? Yeah. I'll repeat again, is the feeling is the patient will need to step through, and that that will be identified before the patient gets to the counter. There's two ways to help. One, we'll have a copay support, and we envision that that copay will be in the range equivalent if you were to get an OTC PPI and take it as prescribed. We don't want a patient to walk away because of a copay, and that'll be for commercial patients. The other thing we're doing is, we plan on partnering with a cloud pharmacy, and cloud pharmacies really came to be during the pandemic. This is not a specialty product.
What they do is they do a light touch on reimbursement, and then any patient maybe who hasn't met their deductible, commercial patient, hasn't met their deductible, for some reason it isn't covered, we will not give away free goods. It will not be a bridge program, but we can, through consignment.
sales, working with that pharmacy, we can provide product to the patient and at the same time ensure that we receive revenue.
Sure. Maybe probably one of the most common questions you'll typically get from investors is, you know, what does the shape of a launch curve look like? You and I have often talked about Dexilant.
Mm-hmm.
the most recent market analog for this particular category. Do you feel like that's still relevant? That was certainly a drug that was launched pre-pandemic. Does that analog, in your mind, still make sense?
I think, you know, we've looked at many analogs as we've tried to, you know, evaluate the launch curve, because particularly in that first 12 months, I think, you know, Dexilant is an appropriate analog, as are many others, like Linzess. I think there's parts of other product launches that we've evaluated. None of them fit perfectly, because this is a really unique opportunity, a very large market, no competition, you know, first-in-class, best-in-class. We're launching, as Martin mentioned, out of the gate with already 60% commercial lives covered for the H. pylori indication. In fact, we already have in one of the large contracts that we have contracted with one of the payers, we already have the bottle, which is a 30-count bottle for erosive GERD already covered as well.
While you can look to some of those analogs, you know, there are other dynamics at play that I think will help us accelerate that first year of launch versus some of the other launches.
Great. Maybe turning to other aspects of the business, you mentioned in your introductory remarks that you are working on lifecycle management for vonoprazan here, including NERD. Maybe you can remind us of the prior data at a high level and how the NERD indication potentially figures into your longer term strategy to maximize and extract value from the asset here.
Sure. Maybe just, before I touch on that, I'll just mention the unique mechanism of action, which really plays into how we've shaped both the clinical program and looked at lifecycle opportunities for vonoprazan. Vonoprazan is unique in that unlike PPIs, it binds to both the active and the inactive pumps, and that really translates to the differences we see in the clinic. The rapid onset of action within the first day are very potent and very durable. And that was how we designed all of the clinical programs to really highlight that differentiation versus PPIs. When we looked at the profile, the first two indications are obviously H. pylori and then erosive GERD.
The third program, which we have read out a positive phase III, is for non-erosive GERD, which is the largest segment. It's around 70% of the patient population for GERD. And there, we're also pursuing a very unique dosing regimen, which is looking at on-demand or as-needed therapy. We're looking at extending the daily dosing study, which we'll read out shortly and plan to file that by year-end. That's the NERD indication, which will have approval next year. Based upon that data, we'll initiate an on-demand or as-needed phase III study. And that will be a highly differentiated versus the standard of care PPI. In fact, the FDA has engaged with us in designing that clinical program because many patients don't want to take their PPI every day.
PPIs have tried and failed. Their mechanism is not appropriate to be utilized in an on-demand or as-needed fashion. This will really present a unique opportunity for the patients that are suffering from these two diseases. The other opportunities for us are looking at eosinophilic esophagitis. I'm in discussions with the FDA regarding a protocol for pediatrics, as well as EoE patients in pediatrics as well as adults. We anticipate initiating that phase II for that patient population. Potentially looking at additional presentations, IV, as well as an orally dissolving tablet. The unique profile for vonoprazan also presents an opportunity way down the track, towards the end of the life cycle of vonoprazan for a switch. That's something we would plan well down the track.
Ultimately, the goal is to displace PPIs. In Japan, where this product has been on the market for several years, vonoprazan is market leader in Japan and has displaced. It was a very similar market dynamics at play in Japan, where they entered into a largely genericized marketplace and really rapidly became market leader. They've got more than 45% share in Japan. the ultimate goal.
That translates to about $800 million.
Correct.
annual sales in US dollars, right?
Yeah. About $850 million, they're selling in Japan, it's still continuing to grow pretty rapidly, driven by volume, about 20% year-on-year. We anticipate that vonoprazan will really present opportunity to radically change the therapeutic options in the US, Europe, and Canada and change the paradigm within the marketplace.
Great. I want to maybe just touch on your comments with regard to the on-demand study that you referenced, and maybe, you know, since PPIs historically haven't worked in that particular application, can you maybe just comment on what the FDA has guided Phathom on with regard to how to approach the on-demand study here?
Sure. We designed the phase II study in collaboration with the FDA. The way we designed the phase II was patients come in, and they're given daily vonoprazan. Those four who respond, those patients who respond, move on to on-demand. On-demand, in this case, is where the patients when the patients have an episode of heartburn, they take vonoprazan. We'll monitor how fast that heartburn episode resolves, and also we'll monitor over the following 24 hours, the absence of return of that episode. We need to not only control it fast, but have the patient free of heartburn for 24 hours. That combined endpoint is what's unique about this study.
Our phase II study showed that vonoprazan, actually, in all those levels we tested, 10, 20, and 40, did achieve resolution of heartburn episode after occurrence as early as 1 hour, and for most patients, that resolution remained over 24 hours. Very separated from placebo. We talked to the FDA. They were actually very pleased and encouraged by that because it's unique elements of the design, but also the unique elements and the rigorous of that endpoint as well, because it's a tough endpoint. Our phase III study that we're discussing with them is largely that phase II design, and the discussion is going really well and we anticipate finalization of that very soon.
Great. Just quickly on EoE, there has been some developmental efforts from biologics such as DUPIXENT and some other antibodies for that particular indication. I guess, as you think about potential development in EoE, would this be as a step before biologics, or do you think it would make more sense in a post-biologics population?
Before biologics. Yeah.
Okay, great.
I mean, you know, phase II will tell us, but that's our intent.
Okay. Maybe to bring Molly in here, you recently did a capital raise, can you maybe comment on, you know, following this raise, where your cash position takes you to? You're obviously on the cusp of commercialization here, so I'm sure that figures into calculus. Then I had a follow-up question for Terrie.
Yeah, as you mentioned, we just announced a $150 million gross raise. That was very well oversubscribed, a lot of interest in the market, that essentially gave us runway through 2025 now. That coupled with the $100 million of debt availability we have and the $175 million under our royalty financing agreement, plus this additional capital, we feel really gives Martin the resources he needs to launch erosive GERD this year and as well as non-erosive GERD next year.
Okay, great. With your capital position, bolstered meaningfully now, Terrie, you know, you've talked about life cycle management. In terms of prioritizing capital, how does life cycle management rank, I guess, relative to business development? As you think about business development, where are sort of the key opportunities or focus areas for you as you think about the longer-term strategy, potentially outside of vonoprazan?
Sure. Our number one priority, in the short term, so I'd say, you know, define that as in the next two years, is optimizing vonoprazan. You know, we believe that, you know, as you look at the number of indications that we have in succession over the next two years, it's really a pipeline within a product. The resources that we have will be really focused on maximizing the launch in Q4 and then going into 2024 with launching the daily dosing and then following up with on-demand, and then EoE. We, we believe, based upon the success in Japan and all of the market research and dynamics that we've seen play out from access perspective, that we have the potential to generate, at peak, more than $3 billion, this compound.
We really want to make sure that we don't spread our resources and focus beyond optimizing vonoprazan. Having said that, in the medium term, and we've done some work to look at the GI landscape more broadly and look at assets, particularly in, you know, late phase II, phase III, where we could leverage the structure that we've put in place, both in Azmi's group, in terms of the expertise we now have in development, and then in Martin's group, in commercialization, to look at assets that are within the GI space that are adjacent to vonoprazan. We've done that work and paying close attention to opportunities that may arise once we become cash flow positive.
In the very short term, all of our focus is in just maximizing the launch and maximizing the opportunity.
Great. We're up on time here, so we'll end it on that note. My thanks to the Phathom team for joining us today. Thank you very much!
Thank you, Paul.
Thank you.