the CFO, Ruoyu Chen, the Investor Relations, Steve Jasper, and with us is also the Clinical and Regulatory Consultant, Susannah Hoyertory. Sorry. As always, this will be a 30-minute presentation. There should be some time at the end for Q&A, so if you do have a question, you can type them into the Q&A screen at the bottom of your, at the Q&A tab at the bottom of your screen. And with that, it's all yours, Han.
All right. Thank you, Jim, and good morning, everyone. Thank you for joining this seminar. My name is Han. My presentation today is about the Gyre Therapeutics. We are a company developing anti-fibrotic therapeutics for chronic organ diseases. And this is our forward-looking statements. Gyre is a U.S. NASDAQ-listed company, and we are controlled by a Japanese company, GNI Japan, and this company controls 85% of Gyre Therapeutics. At the same time, we also owns a subsidiary in Beijing, Gyre Pharmaceuticals, and we own 65% of Gyre Pharmaceuticals. In this talk, I will try to explain how Gyre different from other pharmaceutical companies, our differentiation.
I want to explain our strategies, how we manage and mitigate commercial risk, clinical and regulatory risk, and also product development risk. First, I want to introduce our three commercial drug currently approved. One is Pirfenidone. This one was approved in 2012, and then we've been marketing this drug. We were the leading sales in China. The 2023, the revenue is $112 million, and then this year, the sales is not done yet, but it's on track. So the drug Pirfenidone, it's approved for idiopathic pulmonary fibrosis. Then, there's a second drug, approved, also approved for the IPF, idiopathic pulmonary fibrosis. It's called Nintedanib. Nintedanib currently is marketed by Boehringer Ingelheim for $3 billion a year in the world.
However, this drug is going to... the patent will expire in 2025. To really mitigate our commercial risk, we acquired a generic Nintedanib in May 2024, and this will give us a stronger position in the IPF market. So we are the only company currently owns two approved drugs in the IPF market. And then we also proudly announce we also have the Avatrombopag. This drug targeting thrombopoietin receptor and also indicates for thrombocytopenia associated with chronic liver disease, and this one was approved in July 2024. So now we have three commercial drugs, which give us a stronger position and also a stronger financial support.
Then this slide summarizes our differentiation from other companies and also how we address the risk throughout the drug development process. Number one, we have a proven record. We developed Pirfenidone from research to commercialization, so we walked through this process successfully, which given us a strong track record and also our position in the fibrosis field in China, also in the world. And like I said, we have three commercial products right now, so we are financially sustainable, so which give us a very good security, particularly in this type of economic environment. And then, how we focus our innovation, what's our strategy? We focus on harnessing the chronic inflammation. Chronic inflammation, it's the cause of many, many organ disease, including liver, lung, kidney, and heart, and even neuron.
We target molecules in this pathway, for example, TGF-beta. Basically, we focus in this area, and then we tackle multiple organ diseases. That's our innovation focus. As you all know, drug development, it's a very high-risk process from all the way from target validation to establish a concept, molecular optimization and then clinical trials. There, this process, some people refer it to the valley of death. It costs billions of dollars and more than 12 years to develop a drug. We are a team of really experienced people in the pharmaceutical world, so therefore, our strategy is that we have a de-risk R&D approach.
For example, our lead candidate, F351, Hydronidone, it's derived from the approved drug, Pirfenidone, and then we have a number of drug in the pipeline are in a similar rationale. So in this way, we have already have one foot in the door. We just need to demonstrate how we make this drug better than the approved drug in terms of toxicity and also efficacy. And in fact, our F351 right now is in pivotal 3 trials. The result will be announced in early 2025. And additionally, we have a very rigorous and efficient clinical trial execution in PRC. This allows us to quickly advance our drug program in the competitive world. And also, our strategy is also we want to replicate the China clinical trial success in the US.
So this is the summary, you know, how our company differentiate from other companies and then how we mitigate the risk throughout the pharmaceutical development process. And then to give you just a little bit detail on Pirfenidone and Estuary. So those two drugs, Estuary and the Nintedanib, the only two drugs approved in the IPF. And then the IPF, it's a very big market, and then in this bio, IPF, it's becoming a really competitive field. People are really starting to pay attention to this field. And we are the only company in the world owns two approved drugs in the IPF, so really give us a strong position in the industry. And this is the summary of our pipeline. I have two slides to explain our pipeline.
The first slides are the commercial pipeline. So we have Pirfenidone, Nintedanib, and Avatrombopag. This second slide is really the slide I want to highlight with all of you, because you're interested in our long-term growth. 351 is our lead candidate right now. This lead candidate already completed IND in the U.S., and then we are filing a phase II in the U.S. The filing will be completed before the end of 2024. And then, in China, we have successfully completed a phase II study. The result was published, and I'm going to share a little bit of the clinical result with you in a moment.
Then with that result, we initiated the pivotal phase III, and then the trial right now, the patient's enrollment was completed about a year ago, and then the last patient out will be October 2024. We are going to have top-line result on this pivotal phase III trial early 2025. Our second candidate is IF-523, which is a caspase inhibitor. Caspase is a very difficult drug because caspase is everywhere. However, we were able to show very encouraging results on the acute liver injury in our phase II trial. We just completed the 16 patients, and then we're going to enroll more patients in the near future.
So hopefully, we'll have more patient result, and then we can share with everyone in a few months, and which is at this right now, the result is encouraging. And then we have a F230, which targeting the pulmonary arterial hypertension. And this one, the IND was already approved, and then we are going to start enrolling patients soon. And then the last one on the pipeline right now is a 528, which was also a derivative of a commercial product, and this is going to target chronic obstructive pulmonary disease. And this one, we plan to file the IND soon. So this is about our pipeline. And next, I will spend a couple minutes explaining about our F351 program.
Susannah is our lead in this program, so if you have any questions, she'll be happy to answer your question about this program. The Hydronidone, like I explained, it is a derivative of Pirfenidone, and it targets the TGF-beta pathway... and then it has a more favorable metabolite compared with the Pirfenidone. So then potentially reduce its liver toxicity. And this result actually was validated in our phase 2 trial, and also are going to be validated on our ongoing pivotal trial. Clinical trial development right now on this program, phase 1 was completed both in China and also in the U.S., and then the phase 2 was completed in China for HBV-associated liver fibrosis, and then the confirmatory pivotal 3 trial is ongoing right now.
As you know, the liver fibrosis, it's a very big market. Even the HBV-associated liver fibrosis, there's a very big market in the Asian countries. And this summarizes our phase 1 trial results in the U.S. And then, it has a very favorable toxicity profile. It's very well tolerated in the repeated doses. And then, the phase 2 result was completed, and this result was published. This is a very brief summary of some of the clinical results in the phase 2 trial. As you can see, at the 270 milligrams per day, it has the most significant benefit based on the fibrosis improvement and also by the liver stiffness measurement.
This is the design of our pivotal 3 trials ongoing right now. We are going to have the results ready at the end of 2024, and then we will announce in 2025. Here's a summary of some of the upcoming milestones. Well, I didn't list the commercial milestone, but you know we have three drugs, so the other two drugs will start commercialization very soon. In China, on the pipeline, so we are expecting the pivotal 3 trial results, and we, in fact, have already started the NDA preparation. In the U.S., we have completed the phase 1 trial, and then I forgot to mention, Gyre was listed on Nasdaq at the end of 2023.
We are filing a phase 2 protocol for MASH or NASH-associated liver fibrosis in the U.S. And this one summarizes our highlights of our company. We are a sustainable pharmaceutical company with three approved drugs that will be in commercial very soon. One in commercial already, two will be in commercial very soon. And we are a revenue-generating company. And then we have a very robust pipeline: F351, F573, F230, and also F528. And our lead compound is currently in the pivotal 3 right now for HBV-associated liver fibrosis, and also we are filing a phase 2 study in the U.S.
And then our goal is, since the Gyre was just listed on the Nasdaq, so we want to take this opportunity to tell you our company, and then share our story, and hope some of you will be interested, and then we could engage more in future to explore collaboration opportunities. With that, thank you very much. Any questions?
Great. Yes, we do. Thank you. I want to start with the F351 trial. The first basic question is why are you using a derivative of Pirfenidone and not just using the same compound that you use in China?
That's a very good question. So this is our company's strategy. Pirfenidone, the patent, the chemical patent expired a long time ago, and then, right now, it's really hard to file any patents on Pirfenidone. So the F351 gives us the position so we can protect globally on our new compound. So that, that's the strategy. And also, we also create the new compound that has a much more favorable metabolite, so to reduce the liver toxicity. You know, Jim, as you know, in the chronic disease, it's very different from cancer.
For cancer, you know, the tolerability for toxicity, it's higher, but for chronic disease, people would take the drug for a very, very long time, so there is zero tolerance on the toxicity. So to have a better safety profile in a compound, it's really give us a much stronger competitive edge. That's why we made the 351.
And the existing Pirfenidone sales, those are all in China, correct?
That's right. We don't have a team in the U.S., but however, these are three drugs we are exploring partnering opportunities in the U.S. right now. We want to partner in the U.S. to co-develop our 351 program in the U.S., and also to commercialize the generic Nintedanib, and also the Avatrombopag. Also, we have a very strong sales team in China. We have 500 people right now. Probably we'll hire another 100 people next year. We are one of the strongest sales team, sales network, so we are also interested in collaborating with some company in the U.S. or outside China to help them to commercialize their product in China.
So, we have a two-way collaboration opportunities for Gyre.
If 351 is approved in the U.S., would you, you would seek approval in China as well?
The 351 right now, the Pivotal Three will be done in China very soon. Then, if everything goes well, we anticipate we'll, we'll, we'll have approval in mid-2025 or maybe later, sometime. But that's, that's this is just a hope, right? So nobody can guarantee that. But in the U.S., then we'll start the phase II trial in the U.S., and then advance the program in the U.S. So that, that's the plan for 351.
You mentioned that the patents on Pirfenidone have expired, so are you seeing generics, generic competitors in China right now, or?
For Pirfenidone, there are not much competitor for Pirfenidone right now. But the Nintedanib, since this one just expired in China, and also will expire in the U.S., so people are engaging more into the Nintedanib. And then, that is why we acquired a generic Nintedanib. Yeah, that we predict we'll see more competition with Nintedanib than Pirfenidone.
If you do announce a partnership in the U.S., do you think there's the potential for some, some financing that goes along with that, some non-dilutive financing?
That's a very good question. Yeah, so we have sales in China right now, $112 million last year, and this year, probably something, you know, in that range. And then, that money will be sufficient for us to support our trial in China. But in the U.S., in the long term, we predict we'll need financial support, and then we need both fundraising and also as a business partnership. Whether these two will be together, we don't know. If a large pharma company want to provide the financial support for our U.S. program, that'd be really fantastic.
How big is the market in the U.S. for NASH and for, you know, liver fibrosis? I'm sorry, pulmonary fibrosis.
Susana, you want to answer the question? It's huge, but, Susana, please.
I can answer the question regarding the, excuse me, NASH market. It's right now, based on the latest, probably, about 15 million and more patients affected with NASH, but I think that's an underestimation. With the better diagnostic and more focus on the disease, these numbers going up, but it's huge. Because, right now, we have every, maybe other or third patient that is obese, and if not taken care of, going that pathway toward NASH at one point of their lives. So in other words, it's, it's large. Even with the approved drug, Resmetirom, which right now is growing quite slowly, and it's a question how the doctors will position use of that drug for liver fibrosis versus the metabolic aspect.
So, Jim, for example, recently, Madrigal, their compound, Resmetirom, was approved. And then, there was an analyst predicted if Resmetirom covered just a portion of the NASH fibrosis market, the annual sales could be up to $4 billion or more.
Okay, and the F351, that one would be for pulmonary fibrosis, right? How big is that market?
So Jim, currently, the first indication on the phase III trial right now, right now, it's HBV-associated liver fibrosis.
Okay.
Then, in the US, we are planning for the MASH fibrosis. But, you know, we could also explore HBV-associated fibrosis also. But, your question is... Actually, that's a good question. This drug could also, in theory, also have efficacy on pulmonary fibrosis too.... So it's about, we are not exploring that one at the moment.
Okay, and currently, I looked at your balance sheet, you have about $44 million in cash and investments. You know, how long was that? You know, you know, factoring in your current cash burn, you know, how long does that last?
That's gonna last a long time, and also, we are also a profitable company, so we'll continue have a profit coming in every year. So then, there isn't any concern for our sustainability with the company right now.
So-
Our fundraising in the future is really want to advance the program in the U.S.
Okay, well, that's... And so the phase 3 trial in the U.S., I guess, would be a significant cash drain. Do you have any sense on how many patients would be involved in that, and what it would cost?
We are starting with the phase 2 right now, so we estimated about $12-$15 million to run the phase 2 trial. But then for the phase 3, it really depends on how we stratify the patients, and then that would determine by the statistician, you know, how many patients need to be involved. But that's gonna be expensive trial, yeah. And we definitely need to partner with someone.
So, it sounds like the existing business will support you through the end of the phase 2 trial, and then you'll need financing to complete phase 3?
We hope-
Is that the right way to think about it?
We hope we will raise fund to support our phase 2 trial in the U.S. Yeah, I think with our pivotal 3 trial results, if that result is favorable, which we anticipate, there will be interest from investors to sponsor the trial in the U.S., so that's our plan.
Okay, and then there's several questions about the share price. You know, it's been very volatile over the past few years. It's up right now. You know, what are the factors, you know, that are driving the price right now? Do you have a sense on that?
Yeah, that I know that's a good question. You... The, the, Gyre, you know, we, we, we were just listed in the past few months. And then, as you mentioned, you know, there's a volatility right now. We feel part of the reason is because we, just listed on the- on the Nasdaq, and that, that caused the volatility. And secondly, we have a very low liquidity at the moment. Our controlling shareholder is GNI Japan, who owns 85% of the company. So then, to really, reduce... I mean, right now, the, the stock price seem to, to, more stable right now. And then, a good news is, the, the, the stock was just included into the Russell 2000 and the Russell 3000 about a month ago, so then...
And I hope in the future we could increase the liquidity. And also, with our more product in commercial and also the Pivotal 3 trial, hope that will also support our stock price in the future.
Okay, so, we are out of time. I just wanted to thank you again for presenting and doing meetings with us, and hope to hear from you again soon and get an update on how the trials are going.
Yeah. That's fantastic, Jim. Thank you so much. We'll keep you posted, and we'll keep everyone posted.
All right. Thank you.
Thank you again, everyone, for your time.
Thank you, everyone.