Good afternoon, everyone. Thank you for joining the HC Wainwright 27th Global Annual Investment Conference. My name is Joshua Coarsen, and I'm an Equity Research Associate at HC Wainwright. Today, I would like to introduce our presenter, Fabrice Chouraqui, who is the CEO of Pharming. The floor is yours.
Thank you very much. Good afternoon, everyone. I'm the CEO of Pharming. I have joined the company about six months ago and am very happy, actually, to tell you more about Pharming after the forward-looking statement that you are quite used to. Pharming, for those of you who've known and followed the company for quite a while, has really changed tremendously over the past three, four years. When three, four years ago, it was a one-asset company with a legacy product called RUCONEST. It is now a company with two commercial assets on the market, RUCONEST and Joenja, each growing double-digit, and with a high-value pipeline with two programs with a sales potential of more than $1 billion. This unique combination of high-growth commercial assets and a high-value pipeline really is supposed to deliver strong value creation in the near future.
What attracted me to Pharming and what makes Pharming really unique is the fact that we have this legacy drug called RUCONEST indicated for hereditary angioedema attacks, which has been on the market for 10 years, continues to grow double-digit, and actually provides the cash to allow the expansion of our portfolio and pipeline. Being able to have our destiny in our hands is quite unique in the biotech environment nowadays. Obviously, we will not be stopping with the portfolio and pipeline that I just showed you. Our goal is to create a world leader in rare disease and leverage really the proven capability that the company has developed over the past years, specifically in clinical development, in supply chain, and in commercial. If we look at where we are today, clearly, as you may have seen, the company is enjoying a very strong momentum.
Sales in the last quarter, which we presented at the end of July, grew by 26%. Those revenues, where the growth was driven actually by the growth of our two commercial assets, both RUCONEST and Joenja. We've also, in Q2, delivered meaningful operating profit and generated meaningful cash. As you can see, a big significant improvement compared to where we were last year. As a consequence of this performance, for the second quarter in a row, we raised our revenue guidance, which we expect to be between $335 million and $350 million this year. Let me tell you more now about our two commercial assets, and I'll also spend time on our pipeline since I believe this is where a lot of the value creation relies. Let me start with RUCONEST, the foundational product, as I said.
RUCONEST has established itself as a cornerstone treatment in the treatment of hereditary angioedema attacks. As you probably know, hereditary angioedema is a disease which is caused by the deficiency or the dysfunction of the C1 esterase protein, which is a protease inhibitor that regulates inflammation and immune response. RUCONEST targets the root cause of the disease. What you see here is the three different immune cascades that lead to a hereditary angioedema attack. RUCONEST is the only treatment that targets through all those mechanisms and at different points. That explains the very strong efficacy of the drug. The drug is being used in all types of patients, type 1, type 2, also normal C1, which are difficult-to-treat patients. The valuable position of the drug for patients is very well established.
Just to give you an idea, 97% of attacks are treated with just one dose of RUCONEST, and 93% of attacks are stopped for at least three days. As a matter of fact, given its very strong efficacy, RUCONEST is often used by patients who have failed other treatments. That's a good thing. I know that usually people like to be positioned in first line, but in a highly dynamic market, it's also very good to have carved out a space for yourself when you are a reliable, high-efficacy treatment that patients can trust. That's why there's been a lot of stickiness with RUCONEST and a growing understanding of its distinctive value proposition. That translated, obviously, in its performance. Again, 10 years in the market, the drug is growing 28% year on year.
You can see that growth is coming both from new prescribers, more prescribers using the drug, quarter over quarter, and as a consequence, more new patients being put on the drug. Clearly, a drug that will not be displaced, has carved out a very specific subsegment because of its unique value proposition, and also a drug that has a very specific manufacturing process. It's being manufactured out of the milk of transgenic rabbits. Obviously, something which is not easy to replicate, and I'm not aware of anyone who has attempted to control this very complex manufacturing process. Now let's talk about Joenja. Joenja, a drug which has been on the market now for two years and currently is indicated for APDS. APDS means activated PI3K delta syndrome. It's a rare primary immunodeficiency which is the result of a gene defect on two genes that lead to PI3K delta hyperactivity.
A hyperactive PI3K delta pathway results in dysregulated B and T cell development, which leads to fairly common immune clinical symptoms, severe recurrent infections, lymphoproliferation, a large set of autoimmune symptoms, bronchiectasis, and lymphoma. It is a drug which is life-changing. I must say, I've had the opportunity to meet patients, and it's quite striking as RUCONEST is for hereditary angioedema, but really for Joenja. Here, we're talking about patients who have struggled to get access to a diagnostic and finally can get a treatment option. Joenja is the only drug approved for activated PI3K delta syndrome (APDS). On that slide, you can see actually the burden of symptoms on the left side that a patient can endure. This is actually a summary, a case study of a 20-year-old patient which we have followed over six years on Joenja.
You can see that since that young man has been put on treatment, his life, his disease has improved tremendously. He was able to stop immunoglobulin injection. There was no hospitalization. All his seven infections returned. His blood count actually went back to normal. Perhaps more important, there's been no degradation of his lung functions. Clearly, a drug that really transformed the lives of patients. As a result of those changes, this young man was able to graduate from high school, then graduate from college, and get a job. When you encounter those stories, this makes the job that you do very meaningful. That explains why Joenja actually has had a nice uptake and the prospect for the drug. As you can see, there's been an acceleration of patients on Joenja in the first half of the year.
In the first half of the year, we've had more new patients on Joenja than in the whole of last year. That says a lot about this acceleration of patient uptake. There are actually a number of growth catalysts in the near term. Today, the only source of business are adult patients, 12 years and older, in APDS. There are three very, very well-identified new sources of business that actually will add on top of the existing one. That will be able to actually sustain and even dramatically accelerate the uptake that you saw. First of all, there is the reclassification of VUS patients. VUS means variant of uncertain significance. We have actually figured out that when doctors think that one of their patients has suffered from APDS, they commission a genetic test, and one can expect that that genetic test comes back either positive or negative.
In many instances, that test comes inconclusive. It comes inconclusive because the patient has a gene defect on the two genes coding for the PI3K delta pathway, but there's not been any proof that actually their variant, their gene defect on this gene, is leading to a hyperactive PI3K delta pathway, is leading to a gain of function. We've commissioned some work lately, which has been carried out by Dr. Milner and his team at Columbia University, a few streets up north. That work has been published in Cell in June. Dr. Milner and his team were able actually to identify 100 new variants that are linked to a hyperactivation of the PI3K delta syndrome. That means that those patients, some of these patients who are VUS patients, will be able to be reclassified as APDS patients.
That is obviously bringing actually great hopes to these patients in the absence of a firm diagnosis. It's also an additional source of business actually for Joenja. We assume that over time, about 20% of all VUS patients will be reclassified as APDS. Something also interesting in this publication is that the scientists that carried out this piece of research showed that the prevalence of those new variants is actually far higher than that of the variants that we have known to date. They conclude in the article that the prevalence of APDS could be up to 100 times higher. As you can imagine, a huge upside for Joenja being the only drug approved for this disease. Obviously, we're doing a lot of work right now to understand those data and see how we can explore those data further.
That's the first near-term growth catalyst that is going to kick in in the second half of this year. There is a second source of growth, which is the expansion of the label to the pediatric population. We've completed the trial, which was actually as good as the adult trial in terms of efficacy and safety. We've submitted the NDA to the FDA, and we expect to receive this label expansion, pediatric label expansion, in the first half of next year. Another important source of business, there's about a third of the patients, of APDS patients, that are pediatric. A number of them are already well identified, and some actually are already on Joenja through the ACCESS program. The last growth catalyst is the geographic expansion. We've launched Joenja in the UK. The drug actually is doing extremely well.
We've identified eight countries where we believe that it would make sense to have boots on the ground to launch Joenja because in those markets, the disease is treated in center of excellence. You don't need a lot of resources and get actually a payback fairly quickly. We've just filed the NDA in Japan, and we expect an approval in the EU next year. Overall, you can see that really Joenja is very much a drug at the very early stage of its life cycle. As I said, today, the only source of business is adult APDS. In APDS, there are many more growth opportunities with the pediatric, with the VUS patient reclassification, and with potentially this upside on the prevalence, which could be up to 100 times higher. My hope is to put a number on that in the coming months.
Beyond APDS, we are also studying the efficacy and the safety of the drug in two adjacent indications. In primary immunodeficiencies with immune dysregulation leading to PI3K delta signaling, it's a disease with higher prevalence, five times what we thought the prevalence of APDS could be. We have also another program ongoing in SIBD, and here, we're talking about a disease which is much, much more prevalent. We've picked those two programs. We started those two programs not by chance because clearly there was a very strong scientific rationale. First of all, these are patients which have the same clinical, very similar clinical manifestation as APDS. The unmet need is very high, as I said, and the prevalence is much larger. Clearly, in terms of scientific rationale, in those patients, it is believed that PI3K delta, a hyperactivated PI3K delta, is also part of the etiology of the disease.
What's also interesting is that we've had, we still have a few patients involved in our ACCESS program, compassionate programs, and those patients have been responding very well to the treatment. Obviously, in discussion with the medical community, that was a great incentive to start these two programs. We have two Phase 2 trials underway. We expect them to read out in the second half of next year. It's going to come very soon and clearly could help significantly broaden the opportunity for Joenja. You can see that clearly we have a drug here who could well become the first billion-dollar drug for Pharming. Possibly in APDS alone, that will depend on the true prevalence of APDS, but definitely with those two additional indications. Let me talk now about KL1333. This is an asset that we got from the acquisition of Ableva that we've completed earlier this year.
KL1333 is a small molecule which we are developing for primary mitochondrial disease. These are a group of diseases which are well-known, well-characterized. There are more than 30,000 diagnosed patients in the U.S. and the top five EU countries. What's also interesting is that those patients are treated in centers of excellence. It's not that they are scattered, and you can access them very, very easily. The mechanism of the drug is well-known. I will not go into detail, but in a nutshell, it normalizes the NAD+/NADH ratio. As such, it allows a normal production of ATP, which is actually the root cause of the disease. It's a genetic disease which is caused by a gene defect on mitochondrial DNA. As a consequence, the mitochondria in the cells are not working properly, not producing the energy as they need.
As a consequence, those patients are suffering from very significant fatigue and muscle weakness that completely impair their life. We have a Phase 2 trial ongoing. It's a registrational trial. The two endpoints have been pre-agreed with the FDA. What's important to note is that this program underwent an interim analysis at the end of last year, and it was successful on both endpoints, which obviously de-risked the study. This analysis has been carried out on 40 patients. We've now resumed the enrollment of the trial after the acquisition of Ableva. We expect to enroll 180 patients. We have been actually broadening the number of sites to ensure that all key centers in the U.S. would be involved, which is absolutely essential when you deal with this type of disease. As I told you earlier, the company enjoyed a great momentum, clearly leveraging a very strong growth platform.
We've raised our guidance. You can see here our operating expenses for the year, which include obviously some non-recurring Ableva acquisition expenses. What's important to bear in mind is that RUCONEST is clearly well-positioned to continue to provide strong and predictable cash flows to allow to sustain the development of our portfolio and pipeline, as we intend actually to self-fund all the development of our pipeline and the launch of this drug. Overall, you can see that we've had a very strong start of the year. Sales revenue grew by 33% in the first half of the year. As a consequence, we've updated our guidance, which shows clearly that there are not only our confidence, but also the growth opportunities, not only in the near term, but also in the long term.
The fact that we have a high-value pipeline with two potential billion-dollar programs with Joenja and KL1333, and that there are significant catalysts in the near term. It's not like I am asking you to wait for a couple of years, but clearly, there are a number of very short-term catalysts on growth acceleration for Joenja. There are the two Phase 2 trials reading out at the end of next year, and then KL1333, which will read out in 2027. With this, I'll be very happy to take any questions you may have.
I just had a question regarding your cash position for the company and your intentions going forward as far as M&A and continued.