Hello, everyone. Welcome to BeiGene's Investor Day, to highlight our progress in research and development. My name is Julia Wang, and I am the Chief Financial Officer at BeiGene. We are very excited to host this event, both in person in New York City and online. Thank you very much for joining us today. This is truly an exciting time for BeiGene. As a global, truly integrated, and commercial-stage oncology company, we have reached a meaningful scale and are well-positioned, with strong momentum, to continue the acceleration of our business growth and patient impact. Before we begin, please be aware that during today's event, we will be making forward-looking statements, and our business carries certain risks. You can find more information in our filings with SEC, Hong Kong Stock Exchange, and Shanghai Stock Exchange. Joining me today to present are John Oyler, our Co-founder, Chairman, and CEO.
Dr. Lai Wang, Global Head of R&D, Dr. Mehrdad Mobasher, Chief Medical Officer, Hematology, and Dr. Mark Lanasa, Chief Medical Officer, Solid Tumors. We have a full agenda lined up for you today. John will kick it off and walk you through our path to global oncology leadership. Lai will share with you our approach for delivering impactful oncology innovations. Mehrdad will walk you through accelerating our leadership in hematology. Mark will further discuss our broad and evolving solid tumor portfolio. Lai will take you through our prolific research pipeline and the next wave of new programs and assets. After the presentations, we'll host a Q&A session. The presenters will be joined by Josh Neiman, Chief Commercial Officer for North America and Europe, and Dr. Christiane Langer, Senior VP for Global Medical Affairs at China.
As you might have followed our progress, over the last few years, we have significantly accelerated our progress and growth. Today, the BeiGene story is no longer about the company that will be, but rather it's about the impactful company that we have already become, with an even brighter future ahead. Specifically speaking, we are 10,000 people strong, with top talents operating on five continents. We have clearly built speed and cost advantages with the internalized global clinical development capabilities and have initiated over 140 clinical trials in 48 countries and regions. We are also building global manufacturing capability to support our clinical development and commercialization, including a biologic manufacturing site in Princeton, New Jersey, that is not far from here. Equally excitingly, our financial trajectory and operating leverage have also been very strong.
For perspective, last year, our total product revenue reached almost $1.3 billion, doubled versus the year before. The top line growth was 5 x as fast as the operating expense growth. This trend continued into the Q1 of this year. Going forward, we expect continued robust top line growth and strong operating leverage, further supporting our reinvestment for long-term growth, including into R&D. Throughout today's presentations, we look forward to detailing for you our innovations that are grounded in differentiated science and unmet patient need, while leveraging our global scale and internal capabilities with clear speed and cost advantages. With that, now I'd like to introduce John Oyler, our Co-Founder, Chairman, and CEO. Hi, John.
Thanks so much, Julia. Good morning, good afternoon, and good evening. Thanks for joining our R&D Day today. I'm really excited to share with everyone the great progress that BeiGene's made. Today, I wanna talk about our path to oncology leadership, as Julia said, and I think what most defines BeiGene's path is really our vision. 13 years ago, Xiaodong and I founded BeiGene. At this time, only on 1/6 of the world had access to the latest oncology medicines. Here in the United States, three out of eight cancer patients were unable to afford their co-pays. To us, this was simply unacceptable. We believed strongly in the science and its ability to have huge impact, but we were determined to change the business model to be able to bring medicine more affordably to cancer patients here and around the world.
To achieve our goal, we knew that we needed to approach almost everything differently, and we have. We'll talk about it later, but I think the single biggest lever to doing this is reducing clinical trial cost. Clinical trial costs can account for 75%-90% of all costs of a medicine brought to a patient. We set out to dramatically change this. Today, BeiGene's begun to realize this vision. We have several approved medicines, and we're providing innovative medicine today to over 800,000 patients worldwide. I want to let everyone know this is just the very beginning. To achieve our mission, we knew we had to do things differently, and we set out to build five important competitive advantages. The first advantage was around our research. Research and science are at the heart of who we are.
Our team is one of the largest in the industry, with 1,100 highly productive scientists. We've demonstrated our excellence across a broad spectrum of modalities. Nearly half the programs that we're working on have first-in-class potential. To date, we've received more than $1.4 billion in collaboration revenues. This is over 2.5 x our cumulative spend for research to date, so already our research is a profit center. Secondly is our clinical development. This is critical and central to the success of developing affordable medicines. We've built a team that's fully integrated, it's CRO-free, which is highly unusual, and it's highly productive. It's global. This team includes over 3,000 colleagues across 48 regions, and it's growing. We've run more than 120 clinical trials in-house, and we have over 21,000 subjects enrolled in our studies, and we're cost and time advantaged.
Our goal is none other than to be the absolute leading oncology development organization in the world. Our third competitive advantage is our global commercial footprint. We have approximately 3,500 colleagues worldwide, and our commercial revenue is up 60% in the Q1 of this year over the Q1 of the previous year. Our fourth competitive advantage, of course, is our pipeline. We have great cornerstone medicines in BRUKINSA and Tisli. Both have only begun to scratch the surface of their significant global potential, and BRUKINSA is now improved in over 65 markets. Lastly, and probably the least understood, we have tremendous manufacturing capabilities. This offers us additional speed, cost, and flexibility advantages. I'd like to highlight our $700+ million biologics manufacturing, late-stage research, and clinical development facility that Julia mentioned, which is in Princeton, New Jersey.
As of today, we have capacity that's 55,000 L of biologics manufacturing. We expect this to grow to 74,000 L next year, and it can easily be expanded up to 200,000 L. We also have small molecule production capabilities, with our capacity reaching 600 million capsules or tablets annually by the end of this year. Among our peers, we're one of the few full ADC manufacturing capabilities across all steps of the process. This provides us additional advantages in this exciting new area, which is internally valuable to us, but also makes us an extremely attractive partner for ADC programs globally. We have the entire ability to do this in-house. It's quite rare. Each of these is a clear, sustainable, competitive advantage.
Together, they enable us to innovate with speed and quality at lower cost, which allows us to better serve more patients all around the world. With that in mind, I want to leave you in my opening with these thoughts. First, BeiGene has built one of the largest, most productive and efficient oncology research teams in the industry, and our internal clinical development capabilities, which are extremely hard to build, are cost and time advantaged. The size of our R&D team today exceeds that of many larger companies and is incredibly productive. It's more productive than most others. By way of reference, our oncology R&D team size is close to that size of Regeneron's entire R&D team across all indications, and it's actually substantially larger than the oncology teams at either Seagen or Incyte. Secondly, we have the broadest reach of global clinical trials.
Over the past six years, we've become a leading oncology phase III clinical trial sponsor. We've surpassed several excellent large pharmaceutical companies such as Pfizer, AbbVie, and Lilly. We've actually completed 16 oncology phase III trials in this time period. In running these trials, by our estimate, our clinical trial cost per patient advantage has now been proven to be more than 30% lower than the industry average. Third, the team's productive. We have an innovative pipeline of oncology medicines with 23 development programs and more than 60 discovery programs. From 2020- 2022, we brought more oncology molecules into the clinic than several of our large pharmaceutical company peers. This includes the impressive oncology teams from AstraZeneca, Merck, and Janssen. Looking forward, we expect to bring more than 15 molecules into the clinic over the next 18 months.
This rate could easily make us one of the leading companies in the industry. Most important, these programs are not just large in number, they're very compelling programs. They address unmet medical need, and they have met a very high hurdle to move forward within our company. My last point I wanna make is really about the leadership position that we've built in hematology and where we're going in solid tumors. We now have three impressive post-POC programs in hematology. We've already developed one best-in-class heme medicine, BRUKINSA, and we're developing two others that you're gonna hear a lot about today. We'll also show today that we've built a very strong foundation of highly compelling programs with the potential to establish a similar leadership position over time in several other important solid tumor areas in the upcoming years.
With that, I'd like to introduce our Global Head of R&D, Dr. Lai Wang, to take you through some of this. Thank you.
Good morning, good afternoon, good evening, everyone. Thanks for joining us today. As John talked about a moment ago, BeiGene has ambition to become the global leading oncology company. This needs to start with R&D. Over the past decade, BeiGene has built a large oncology-focused research team, with now around 1,100 innovative scientists working in the lab. The major expansion happened in the last three to four years, which is translating into a burst of new molecules into the clinic. The team is on track to deliver 10 globally competitive new molecule entities a year to the clinic, starting from 2024. Today, I will show you examples of the new compelling molecules discovered by this research team. I will demonstrate to you that this is not only one of the largest, but also one of the most productive research teams in the world.
We believe the most critical experiment in drug discovery is the clinical proof of concept study, which is also the value inflection point for our drug candidate. BeiGene strive to deliver clinical POC faster, with high quality and at a lower cost. Our in-house manufacturing capability and the CL- free clinical development model can reduce the overall cost by at least 1/3, the shortening the timeline for a pre-clinical candidate, PCC, to clinical proof of concept for more than six months. With the success of BRUKINSA, BeiGene has established our position in hematology oncology, especially in indolent B-cell malignancies. To complement and synergize with BRUKINSA, our scientist has invented two other high-impact molecules, the BCL-2 inhibitor, sonrotoclax, and the BTK degrader, BGB-16673. These molecules are also expanding BeiGene's portfolio into other heme malignancies, including AML, MDS, and multiple myeloma and aggressive B-cell lymphoma.
On the solid tumor side, BeiGene has gone beyond IO. We have now built a deep pipeline of oncogenic signaling, targeted therapies, and the tumor-associated antigen TA driven therapies to complement our strong IO portfolio. I'm not going through the pipeline slides in details. We have a leading hematology pipeline with three important programs. A best-in-class BTK inhibitor with BRUKINSA, compelling efficacy and safety with sonrotoclax, and the BTK degrader, BGB-16673, with proof of concept in clinic. Our broader and innovative solid tumor portfolio is growing rapidly. We're expanding into additional tumor types with novel programs, including many targeted therapy. On the latest side, tislelizumab is leading the way with nine part of phase III readouts. For TIGIT, we are focusing on phase III in first-line non-small cell lung cancer with PD-L1 expression.
There are three collaboration programs in late stage developments, including sitravatinib, a multi-kinase inhibitor in collaboration with Mirati, zanidatamab, a HER2 bispecific, in collaboration with Zymeworks, Jazz, and Tarlatamab, a DLL3/ CD3 bispecific antibody, in collaboration with Amgen. In today's R&D section, there are three parts. First, our Heme CMO, Dr. Mehrdad Mobasher, will share with you new compelling data from our three key Heme programs. Second, our solid tumor CMO, Dr. Mark Lanasa, will discuss the progress in RO, as well as the evolution of our solid tumor portfolio. Finally, I will come back to discuss a few new exciting molecules freshly out, coming out of our research. Now, I'm going to hand this over to Mehrdad to talk about our hematology portfolio. Mehrdad?
Thank you, Lai. Hi, everyone. I would also like to welcome you all to BeiGene's R&D Day today, and thank you for spending some time with us, as I will be talking about our leading hematology pipeline. As I also discussed before, we believe that we are well-positioned to be a hematology leader in numerous indications with our current pipeline. We are here to show you our current foundation, what our near future direction is, and where we are headed as a leader in developing medicines in many hematological malignancies. In summary, we have cemented BRUKINSA as a best-in-class BTK inhibitor in CLL, a preferred option based on superior data.
We will solidify our leadership in CLL with the other two assets, sonrotoclax, our BCL-2 inhibitor, and our BTK CDAC, while we'll be amplifying our impact in other B-cell malignancies with progressive treatment strategies, including fixed duration or rational sequencing, and expand our footprint into other hematological malignancies. With sonrotoclax, we will be developing an AML, an MDS, and multiple myeloma, and our BTK CDAC, we can expand to high-grade lymphomas, including Richter's transformation and large B-cell lymphomas. We believe that we are an emerging global leader in hematology with our hematology pipeline of differentiated assets. Number one is BRUKINSA. We have shown superior and durable efficacy and safety across indications, including head-to-head studies.
BRUKINSA has the broadest label among all BTK inhibitors, with four indications that you see: CLL, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia, and is the first BTK inhibitor with compelling data in follicular lymphoma and now accepted filings in the United States and Europe. From the business side, BTK class is expected or projected to have $15 billion by 2028. Our BCL-2 inhibitor, sonrotoclax, also has the chance to be a best-in-class. We have already enrolled more than 500 patients and have compelling data across different indications and different combinations. Based on these compelling data that we have collected, we are initiating a phase III study in treatment-naive CLL that I will talk about later, and also fast-to-market strategies in Waldenström macroglobulinemia and mantle cell lymphoma.
We will also develop this medicine in AML, MDS, and multiple myeloma. Specifically, sonrotoclax has characteristics that can make it a best in class, give the potential for broad use in any practice. BCL-2 business opportunity is currently expected to be $4.5 billion by 2028, and that's despite the challenges that the current BCL-2 inhibitor has in practice. Last, we have utilized our expertise in BTK and approached a target with a novel mode of action and developed BGB-16673 with our CDAC platform. This medicine, our BTK CDAC, is the first CDAC that has entered clinic. We have enrolled more than 50 patients in this program, We have already achieved a proof of concept based on encouraging clinical data that I will talk about later.
We have a robust clinical development program. We expect to start at a pivotal cohorts by next year. As a BTK degrader, this medicine has a potential in diseases like Richter's transformation and large B-cell lymphoma, where BTK inhibitors don't have proven efficacy. We are starting our target population with BTK-resistant patients. Again, given the potential this specific mode of action has, we have the chance to broaden our target population. With that summary, I would like to focus on BRUKINSA, our BTK inhibitor that was designed to be best-in-class and now has demonstrated to be best-in-class with single arm and randomized trials, and now has a broad set of indications around the world. We had a hypothesis. That was around sustained inhibition of our target.
Our scientists at BeiGene worked on engineering and designing and rational dosing of a BTK inhibitor that exhibits high potency, kindness, selectivity, and bioavailability. With that hypothesis, that's how we were working on reducing off-target toxicity and maintaining continuous BTK inhibition to increase efficacy. With that in mind, we took BRUKINSA to a large clinical development program and enrolled a lot of patients in 35 trials, and have consistently shown good efficacy and superior safety. We have had two bold, what I call head-to-head studies, including the first one, ALPINE study in relapsed refractory CLL, that has shown superior PFS and safety, that I will talk a little bit about it later. An ASPEN trial in Waldenström macroglobulinemia.
We have presented long-term follow-up of this study, and we show more durable and deeper responses with in ASPEN trial, which has made zanubrutinib or BRUKINSA a standard of care in this disease. We continue to expand our development programs with BRUKINSA, with rational combinations, including our own assets, including sotorasib, in several hematological malignancies. This slide shows a list of BRUKINSA pivotal trials that are ongoing across five different indications. Some of these studies have already read out, and we have approvals based on those, including our CLL, and as I mentioned, Waldenström. Some are still ongoing, including the MANGROVE study in frontline CLL, that's assessing BRUKINSA with rituximab.
We just had the results of the SHINE study of ibrutinib plus chemotherapy, and that ibrutinib lost their indication in mantle cell lymphoma because of increased toxicity when they were combined with chemotherapy. We are combined with rituximab, and in early studies we saw good safety. Of course, we are now entering follicular lymphoma. PFS analysis from ALPINE study, showing PFS superiority, was presented last year at ASH 2022, as a late-breaker abstract, given the importance and the impact of this data. We were not surprised when we saw these curves, as we had confidence in this molecule all the way to the way that the molecule was designed based on our hypothesis.
This Kaplan-Meier curve that we showed at ASH was with a median follow-up of 29.6 months, which is a very meaningful follow-up in relapsed refractory CLL. Today I'm announcing that we have continued our study, and we will submit an abstract to upcoming ASH meeting with a longer follow-up. Based on incoming data, we are confident that separation of these Kaplan-Meier curves will continue similarly, and the impact of PFS is sustained now with three-year follow-up. We were particularly interested in a high-risk population or high-risk subset of CLL, with deletion of 17p or TP53 mutation, as these patients are known to have poorer prognosis. Where we see the impressive PFS superiority of BRUKINSA versus ibrutinib, with risk of progression or death decreased by almost 50%.
We usually discourage cross-trial comparisons. Since there are a lot of interest in knowing how BRUKINSA behaves versus acalabrutinib, I think this curve is a good curve to look at, and we can compare it with a curve that acala has shown in ELEVATE-RR, their study population limited to 17p deletion population. They have published that curve in their supplementary publication. There are two important things to see there. One is that the ibrutinib arm of ELEVATE-RR is exactly the same as how you see ibrutinib in this study. The second thing is, their hazard ratio when they compared ibrutinib versus acalabrutinib, the hazard ratio was one, and they only showed non-inferiority. Here you see the superiority of BRUKINSA.
In ALPINE study, zanubrutinib BRUKINSA was more tolerable than ibrutinib, more patients in the ibrutinib arm had treatment discontinuation and treatment dose reduction. However, that is not the reason for our PFS superiority, unlike what you might hear from some of our competitors. What we did was that we did several safety with efficacy sensitivity analysis, we factor in all those safety issues, as you can see, including accounting for treatment discontinuation or drug interruption. You see, consistently, PFS is superior with BRUKINSA. That shows that our superiority of PFS, consistent with the overall population, is a true PFS superiority and has nothing to do with tolerability of our medicine. Important safety finding in ALPINE was BRUKINSA's favorable cardiac safety profile that we showed at ASH and we presented in New England Journal of Medicine.
Most importantly, there was no death due cardiac events with BRUKINSA. We have followed this study longer and with a longer follow-up safety data that will also be presented to ASH. Based on the incoming data, we are confident that the cardiac safety profile of BRUKINSA will be similarly favorable. Okay, another way that we looked at the safety data of BRUKINSA in our entire program, is what we call it EAIR or Exposure- Adjusted Incidence Rate, which is a method that factors in exposure time and can provide incidence over a fixed period of time to enable comparisons. As I mentioned, ibrutinib was sometimes discontinued, so sometimes shorter duration. Some of the BRUKINSA patients remained on treatment longer, we wanted to see over a set fixed period of time, how do they compare?
As you can see in this graph, that I'm not going to go through all the details, both in terms of hypertension and atrial fibrillation, BRUKINSA has less hypertension and less atrial fibrillation when compared to ibrutinib. In fact, for the atrial fibrillation, the difference even statistically significant, as you can see, a P value associated with it. BRUKINSA has shown consistent, impressive efficacy across all indications and has shown superior to alternative therapy. This also includes follicular lymphoma. Based on ROSEWOOD Study, we are now the one and only BTK inhibitor that has an SNDA accepted by the U.S. FDA, as we just recently announced and previously accepted by EMA.
You see here the long follow-up of the ROSEWOOD study that we just presented at the ICML conference. We see that the median follow-up of 20 months, the primary endpoints of overall response rate and CR are both clinically and statistically superior when you compare BRUKINSA plus obinutuzumab versus obinutuzumab. You also see the curve for duration of response as assessed by RRC, that's clearly superior in the BRUKINSA plus obinutuzumab arm. We are very excited about this data and potentially giving this treatment to patients with follicular lymphoma. To summarize, BRUKINSA superiority is core to our hematology franchise right now. In treatment-naive CLL, we have data from SEQUOIA Trial that led to approval in treatment-naive. We just showed this data, longer follow-up of this data this summer and has been listed as NCCN Category One.
We have conducted two head-to-head trials that I talked about in relapsed refractory CLL. We are excited that we will send follow-up data from this study to ASH this year. Of course, Waldenström macroglobulinemia. In other indications, we have consistent, superior safety and efficacy data that has led to accelerated approvals. We have ongoing pivotal studies to convert and expand our label in mantle cell and marginal zone, as I mentioned. We're seeking approval in follicular lymphoma based on positive pivotal data from ROSEWOOD. We also have a Phase III study in that. BRUKINSA is central to our future clinical development in several indications, as now we have medicines that can be combined, including sonrotoclax, and improve outcome of patients with B-cell malignancies.
With that, I want to focus on sonrotoclax, that used to be called BGB-11417, which is our novel BCL-2 inhibitor that also has the potential to be best-in-class. The story of sonrotoclax is very similar to how I described BRUKINSA. Again, our scientists at BeiGene specifically designed a molecule, the characteristics that can lead to its being best-in-class. Specifically, sonrotoclax is more potent than the current available BCL-2 inhibitor, venetoclax. In preclinical models, we have seen superiority in BCL-2 net, the wild type, and specifically impressive activity in venetoclax resistance models. It is selective against BCL-2 only and not the other members of BCL-2 family, and this can be important in tolerability of this drug. As I mentioned, it has characteristics that can potentially enable broader use among all healthcare providers.
Specifically, venetoclax has a very long half-life of 26 hours and also accumulates in peripheral blood. That leads to the very known and important risk of tumor lysis syndrome with venetoclax, and that's why, in patients who receive venetoclax, they need labor-intensive lab checks at baseline, late hours of eight, end of the day, the next day, and the ramp-up is slow. Sonrotoclax, on the other hand, has a shorter half-life of five hours and doesn't accumulate in the peripheral blood. That has enabled us to aggressively work on shorter ramp-up and less blood checks, particularly those late hour blood checks are not going to be necessary. This can be used by all physicians, whether they're in community or academic practice.
We have already treated more than 500 patients in trials with sonrotoclax across different indications and combinations, and we are consistently seeing deep and durable responses, which speaks to the potency of this drug. Importantly, combinations, including combination with BRUKINSA in CLL, has been very safe and tolerable and induces deep responses. As a leader in B-cell malignancies, we believe that sonrotoclax strengthens our leadership position in these B-cell malignancies. We have already designed and planning on starting a phase III registrational study in CLL, testing a fixed duration of sonrotoclax plus BRUKINSA that I'll talk about a little bit later. We also have potential registrational opportunities in post-BTKI indications. Patients will receive BRUKINSA , and then after that, they can get sonrotoclax. This include phase II in mantle cell lymphoma that is currently enrolling a phase II study in relapsed refractory CLL in China.
These are indications that venetoclax currently doesn't have, and also an unmet population in Waldenström macroglobulinemia. We are developing sonrotoclax in AML and MDS, both in combinations and multiple myeloma in combinations. That will expand our hematology lead position outside B-cell malignancies. It's important to note that venetoclax currently doesn't have an indication in multiple myeloma and MDS yet. We have an extensive global development program with sonrotoclax, with many studies well for this drug. I'll briefly talk about some of them. On the top you see our study with B-cell malignancies. I'll talk a little bit more about this study, and I'll present some new and compelling data that has enabled us design our phase III study.
Below that, you see a study in multiple myeloma patients with translocation 11; 14. Today, I'll present some new data from this study in combination with dexamethasone. Below that, you see our study in myeloid malignancies, we specifically presented some data at ASH 2022, and we showed even at the lowest dose of 40 mg, we had complete remissions that were durable. That gives us a lot of confidence about future of this medicine in acute myeloid leukemia and also MDS. I've listed the pivotal studies that I talked about in red, I'll talk about a couple of them later. We have a comprehensive design for this first-in-human study.
We have one study globally, that we call it 101, and a study specifically in China for dose finding in Chinese population, as is required by the health authority in China. This comprehensive study, that I'm not going to go through all the details, was designed to answer many important questions, including in CLL. We want to find out our dose, optimize our dose. We want to find the most optimal ramp up, as I was discussed before, that is very important, and the best rational combination, and I think we have achieved all of those. We have determined a recommended phase II dose, and we have done a comprehensive dose optimization with the 320 mg dose and the dose below that, which is 160 mg, to fulfill the requirements that the FDA and other health authorities have from us.
Today I'm showing new efficacy data from the CLL part with sonrotoclax. We started enrolling patients in this study with relapsed refractory monotherapy, then relapsed refractory combination of sonrotoclax, and then combination of sonrotoclax and BRUKINSA in front line CLL. I want you to look at the overall response rate in the treatment-naive population, which is 100%. Every single patient that was treated with this combination had a response. I also want you to look at the high rates of complete remission, CRs. CR is a meaningful endpoint in CLL and is known to correlate with outcome. I want you to look at the relapsed refractory cohort, because this cohort was started before the treatment naive and has a longer follow-up, and the CR rate is impressive at 44%.
We know that longer treatment with BCL-2 inhibition deepens the response. We are confident that our responses will be around the same or higher in treatment-naive CLL as we continue this cohort as well. More important than CR in illustrating deep responses in CLL is eradication of minimal residual disease. Undetectable MRD is known as a very important endpoint in CLL. We call it a surrogate endpoint. We know that it correlates directly with PFS and even overall survival. Here I show the rate of undetectable MRD in treatment-naive patients at the dose of that 320 mg, which is a recommended dose, and the dose below that, the 160 mg dose. You see, the rate of undetectable MRD at 320 mg, a recommended phase II dose, is 65%.
As I mentioned, the 160 mg dose was started before 320 mg. We looked at the patients who have reached a 12-month landmark, which was because that was the landmark that we were interested for a fixed-duration treatment. MRD negativity in that population is 69%. We know that undetectable MRD rate increases with increased dose. We also see that those MRD negativities are coming sooner in our dose with 320 mg, all giving us confidence in the dose of 320 mg than the overall future of this combination at the 320 mg in treatment-naive patients. This is the PFS curve. Looking at PFS, which is the gold standard endpoint in CLL, PFS is 100% among all patients that were treated with 160 mg and 320 mg in treatment-naive patients.
You see that we enrolled 94 patients that were evaluable for this assessment in treatment naive, not a single patient had progression on this treatment so far. I'm acknowledging that some of the durations, follow-up is short in, particularly in 320 mg, but this gives us a lot of confidence. About safety, monotherapy with sonrotoclax and combination, both in relapsed refractory and, treatment naive, has been safe and tolerable. We have enrolled about 100 patients in treatment naive in this combination that you can see, and this cut and re-relapsed refractory. It's important to see specifically, we have no report of tumor lysis syndrome. It's also important to know, the similar combination of a BCL-2 inhibitor and BTK inhibitor, it is venetoclax plus ibrutinib. It does not have a label in the United States, given increased toxicity.
Even though it has a label outside the United States, its use is becoming less and less, and that's because we are learning a lot about the toxicity that is associated with this combination. We looked specifically at the toxicity that are known with venetoclax and ibrutinib, and we don't see that. When we put two safer and better BCL-2 inhibitor and BTK inhibitor of sonrotoclax and BRUKINSA together, we don't see complicated neutropenia, neutropenic fever, and sepsis. We don't see infections, and we don't see GI toxicities that are associated with the venetoclax plus ibrutinib that patients hate, including diarrhea. The totality of data that I showed you of efficacy, including the ORR, CR, undetectable MRD, and, of course, PFS, and the safety that has I showed you, has given us a lot of confidence about our next step.
We have designed the study that you see here that we will be enrolling previously untreated patients and will randomize them to a fixed duration of BRUKINSA plus sonrotoclax versus fixed duration of venetoclax plus obinutuzumab. I have to stress about the importance of fixed duration. Patients and physicians and health authorities and patient advocates and all, are very interested in fixed-duration treatment for a subset of patients. That's why we wanted to have a fixed-duration option for our patients and compare it to the most potent fixed-duration regimen that's available, which is venetoclax plus obinutuzumab. We showed impressive data from venetoclax plus obinutuzumab, and I say we because I was involved in development of venetoclax, and that was published in New England Journal of Medicine.
I have to acknowledge that its use has been very limited, given the issues that we have with delivering venetoclax plus obinutuzumab. We have confidence that we can beat venetoclax plus obinutuzumab in terms of efficacy, in terms of PFS, which is the gold standard, as you can see, the primary endpoint of this study, and we'll have two oral medicines. Both of them have shown superior safety, and we will of course, look at a series of secondary endpoints, including undetectable MRD, as I mentioned, is a surrogate endpoint, and we'll see how health authorities will eventually evolve with undetectable MRD.
This study design has already been discussed and okayed both by U.S. FDA and EMA, is very well on its way to initiation, and we are confident that we will start this study and start enrollment before the end of this year. I want to talk a little bit about multiple myeloma. We all know that multiple myeloma is a disease that we are not curing yet. That means we have a lot of multiple myeloma patients, because they all go through several times of progression, and even though treatment with multiple myeloma has improved so much over the past few years, all multiple myeloma patients continue to receive many lines of treatment. That shows that there's a huge pool of multiple myeloma patients and still an unmet need.
There's a subset of the multiple myeloma that they have translocation 11; 14, and these subset of multiple myeloma patients are specifically very dependent on BCL-2. There's a rationale to combine BCL-2 inhibition with dexamethasone because that makes the multiple myeloma cells more susceptible to this treatment because they are more dependent on BCL-2 inhibition. We have this part of this study, the 105 study, and you can see the dose escalation part of this study that combines dexamethasone with sonrotoclax. Today I'm showing for the first time some compelling data that we have from dexamethasone plus sonrotoclax. I want you to look at the 640 mg bar that shows we have high ORR of 70%, but more importantly, the deeper responses.
In multiple myeloma, specifically, deep responses of VGPR, CR, and what we call it stringent CR, are very important and are known to correlate with outcome, and we are very happy and excited with the data that we see here. As a comparison, I've put the venetoclax monotherapy data in translocation 11; 14, that shows an ORR of 40%. This study, as I showed in the previous slide, will have an expansion of the dexamethasone plus sonrotoclax, and also a separate part of this study that will also combine with the most potent proteasome inhibitor called carfilzomib. You heard briefly from Dr. Lai Wang about some of our chimeric degradation activation compounds, or CDACs. BGB-16673 is the first compound that has entered clinic, and I'll talk about it today, and it's a BTK degrader.
CDACs are bivalent molecules that co-opt a normal process that leads to degradation of the protein. You see a very simple cartoon in the bottom that basically brings something with your target and leads to the degradation of the protein. The only thing I want to talk about based on this cartoon is that it's very different than a BTK inhibitor because it completely degrades the protein. In our case, it degrades BTK, and it will affect B-cell receptor pathway that the cancer cells are dependent on. As you can see, the degraders, our BTK CDAC, is agnostic of the mutations, and that's very important sequencing.
Regardless of what BTK inhibitor, what covalent BTK inhibitor patients receive, BRUKINSA or anything else, this medicine can be given to them, and none of the mutations that we're talking about now are going to be relevant. Because of degradation of the protein, it has the chance to be even more potent than the conventional BTK inhibitors. And I also want to compare some of our characteristics with the competitors that are out there in the degradation platform. You saw some data at ASH from one of our competitors that had a BTK degrader, but our compound compares to theirs, doesn't have IMID activities. Therefore, we know that we are not going to see the safety issues that they had, and that gives us more confidence about the future of this medicine.
We have put together a robust clinical development program with this molecule, and we're executing very well. We have two clinical trials, again, one global and one specific for dose findings in China, and both of them are enrolling very well, and there's a lot of excitement in the community, and we have enrolled 50 patients so far in this trial. We are very well set to start the pivotal cohorts of this study that I will show later by 2024, and we're working on opening combination arms of this study, particularly in combination with sonrotoclax also next year. That will also potentially expound our presence to diseases that the conventional BTK inhibitors have a rationale, but haven't been proven to be successful, in inducing response, and that includes Richter's transformation or large cell lymphomas. This is a study schema.
I only want you to look at the diseases that are listed. A wide variety of B-cell malignancies are enrolled in our dose escalation, and then what we have, what we call a dose, we call a safety expansion, again, in order to the dose optimization that is required from us. We have the two predefined cohorts in dose expansion, that these are the cohorts that I say they have the potential to be pivotal, both in relapsed refractory post-BTK inhibitor in CLL and mantle cell lymphoma. We have achieved early proof of concept with PK and PD markers with this drug. Not shown on this slide, but in our PK, we saw dose-dependent increase in the concentration of our drug, which is what we want to see typically when we do a novel drug.
We have a long enough PK that gives us confidence that this will be a once-a-day treatment. I've been showing the PD markers in this slide. We looked at the protein degradation, both in peripheral blood and lymph node, as a marker of our degradation. You can see peripheral blood on your left-hand side, and you can see lymph nodes on your right-hand side. When we looked at the steady state in peripheral blood, we had 100% BTK degradation at the lowest dose that was tested. When we look at the lymph nodes, at the dose of 100 mg, we only had 20% malignant cells with BTK expression, and when we looked at 200 mg dose, we only had 1% of BTK remaining.
As I mentioned, the dose escalation continues, we will continue to collect data on our PD model as well. In a phase I, it's important to discuss safety. I'm showing safety from our 101, the global study only. In this heavily pretreated patient population that typically has a low reserve, we only had one single DLT that was rash. Majority of our adverse events were hematological, as it was expected in this population, both from the disease standpoint and of course, the treatment that they were getting. Again, important to know, we didn't have any of the adverse events that our competitors have shown. We have had no hypertension and no atrial fibrillation, and we only see some very low-grade fatigue with this treatment.
You also see the data on efficacy that I'm presenting for the first time. I want you to look at our preliminary overall response rate by dose on your left-hand side. Also, you can see, this patient population had a median pretreatment prior treatment of four. I want to draw your attention to the numbers of overall response rate you can see, and particularly how it increases from dose of 50 mg to 200 mg. The cohorts of 350 mg and 500 mg are early, the data is not mature. You can also look at the ORRs from the disease standpoints, all of the diseases that we have treated, from follicular lymphoma to marginal zone lymphoma and Waldenström. This is an important slide that I want you to look at.
While ORR is, of course, very important and we are happy with the impressive data that I showed in the previous slide. In this slide, I'm showing the streamline plots in combination with patient profiles. On your left-hand side, that heat map looking, you see a patient's profile and any treatments they have received before. Almost all these patients have received a covalent BTK before. You only see a few lines, the patient didn't receive covalent BTKs, and all of them are follicular lymphoma. A lot of our patients also received venetoclax before coming on these trial, and you see some of our patients even received non-covalent BTK. With those, you see that the majority of patients had response, and the responses were durable, and patients are remaining on treatment. I want to draw your attention to a couple of these lines.
All the way on the top, you see at our very first dose of 50 mg, we had a patient with mantle cell lymphoma that had received covalent BTK before, had a response, continues to be in response and remains on the trial. A couple of lines below that, in 100 mg, you see a Waldenström macroglobulinemia patient who progressed on zanubrutinib and pirtobrutinib, and when entered this trial, he had a response. The response is deepening and patient stays on treatment. There's a similar pattern in the CLL patients below that and many other examples, but I'm not going to go through all of that. These data gives us confidence that BTK CDAC is a viable option for patients who have diseases that are exclusively sensitive to BTK, but they have progressed through conventional, either covalent or non-covalent BTK inhibitors.
Just as a summary, we have very good safety. We are happy with the toxicity profile. Early, that what we see gives us a lot of confidence. We have no hypertension or atrial fibrillation, as I mentioned, and we have proof of concept, given the promising efficacy data and PD marker data that I showed you. In a very heavily pretreated patient population, as I mentioned, all of them have received covalent BTK, and a bunch of them had non-covalent BTK. I've mentioned and I talked about our current leadership in CLL and how we're solidifying our leadership in CLL. I want to talk about the journey of CLL patients and how I believe every CLL patient, during their journey with their disease, will have the opportunity to have a best-in-class, safe, and efficacious treatment with a BeiGene medicine.
Of course, CLL patients are diagnosed, a lot of them are in watch and wait for a while, and then they start getting treatment for their treatment-naive CLL. On the top, you see BRUKINSA. A subset of patients will get BRUKINSA up to progression. Now, with us developing a fixed duration of BRUKINSA and sonrotoclax, some patients have the chance to get that fixed duration treatment. We are also going to be assessing the role of CD20 in addition to do the doublet or CD20 with sonrotoclax alone. We know that a lot of patients enjoy a long progression-free trial, survival now with these novel medicines, but unfortunately, some CLL patients progress, and they are in need of another line of treatment. We are happy that we are a pipeline. We have several options for relapsed refractory CLL patients and physicians to choose from.
We can have our BTK CDAC with or without sonrotoclax, depending on what they got in their prior treatment. We can have our BTK CDAC with or without CD20. this fixed duration treatments can be repeated. There's data from venetoclax, and we know and we are confident that our patients can get our combination in relapsed refractory setting as well, and we will be testing sonrotoclax in combination with BCL-2 inhibitor as well. With that, I hope that you leave this meeting with these key takeaways. BRUKINSA, as the best-in-class BTK inhibitor in CLL, is based on SEQUOIA and, of course, ALPINE data, adding to our confidence, whose durable, superior efficacy and safety versus ibrutinib. We will be bringing forward sonrotoclax, our BTK CDAC, similarly to patients who need these treatments.
We will develop evidence to support impactful and desirable treatments, strategies, including fixed duration and important rationale sequencing. We will expand our footprint with sonrotoclax in AML, MDS, and multiple myeloma, as I discussed, and our BTK CDAC in aggressive lymphomas of Richter and diffuse large B-cell lymphoma. With that, I want to thank you for your attention and invite my colleague, Dr. Mark Lanasa, who will talk about our pipeline in solid tumors.
Thank you very much, Mehrdad. Thank you all for joining us again. Thank you again for joining us this morning. My name is Mark Lanasa, and I'm very glad to present the progress and potential of our solid tumor portfolio. We have three areas of focus at our solid tumor portfolio. The first is that we continue to have very positive news flow for tislelizumab, our PD-1 antibody, and we're looking to turn that positive news flow into regulatory approvals and ultimately patient impact. From there, we want to build upon tislelizumab to develop best-in-class regimens with new IO targets in our next wave immuno-oncology portfolio, including targets that we're disclosing today, including CCR8, DGKζ, and PVRIG.
From there, we want to expand into additional tumor types with novel agents, some of which we believe have blockbuster potential, such as a CDK4 selective inhibitor in breast cancer. Tislelizumab is an outstanding PD-1 inhibitor and in fact is already a successful medicine. We have treated over 750,000 patients with commercial tislelizumab to date, and we have enrolled over 12,000 patients in our global clinical development programs. We are developing a subcutaneous injection formulation for tislelizumab that will achieve first human dose later this year, so that we can bring the impact of tislelizumab to more patients globally. The data for tislelizumab continues to be very positive. Indeed, every phase III study that we have initiated with tislelizumab has met the primary endpoint.
We have recently announced that the RATIONALE-305 study in frontline gastric cancer met the primary endpoint of overall survival in the intention-to-treat population. Similarly, in the RATIONALE-312 study, that study also met the primary endpoint of overall survival in the intention-to-treat population in a study of extensive stage small cell lung cancer. Again, we're working hard to turn these positive data into regulatory approvals with our partner, Novartis, are happy to inform that the FDA has completed their on-site GMP inspections for Tisli manufacturing, and the BLA review is progressing, as well as the regulatory reviews are also progressing in EMA. Importantly, regulatory submissions are now also underway to expand tislelizumab to the rest of the world in markets such as Australia, Brazil, and South Korea.
As John mentioned to you earlier, this is all being accomplished at reduced cost through optimization, internalization, and scale. Where do we go from here? At BeiGene, we believe that PD-1 is the beginning of the story in immuno-oncology, but it's not the complete story. PD-1 has definitively been a transformational mechanism within solid tumor oncology. One of the challenges that we have in solid tumors is that the human immune system is highly complex, and therefore we have developed a rational but focused program whereby we are modulating different components of the human immune system in a way that can address different patient segments, because the immune system is dysregulated in different ways across different tumor types.
If you'll hang in there with me for a moment, I'm about to take you on a brief but deep dive of our current solid tumor portfolio in immuno-oncology. To start with TIGIT, while we acknowledge that the recent data flow with TIGIT has been mixed, we have completed enrollment in five randomized phase II studies, and therefore, we will have in-house data that will allow us to understand the opportunity landscape for ociperlimab. Additionally, our phase III study in PD-L1 high non-small cell lung cancer continues to enroll very well, and we will complete enrollment this year. In short, we're delighted to have retained the global rights for ociperlimab. From there, for our next wave of molecules, we are working towards establishing proof of concept in a focused and cost-effective manner.
We are upscaling our LAG-3 program substantially this year with phase II studies underway in both frontline and resectable non-small cell lung cancer, frontline esophageal cancer, head and neck cancer, as well as frontline colorectal cancer maintenance. TIM-3 is another co-checkpoint inhibitor. We have established a phase II dose not only in combination with tislelizumab, but also as a triplet in combination with LAG-3. We are testing both that doublet and the triplet in frontline head and neck cancer. We're very excited about our OX40 molecule. The reason for that is that we have the only OX40 agonist monoclonal antibody that does not block the interaction between the OX40 and its ligand, the OX40 ligand.
We have established a phase II dose, both as monotherapy and in combination with tislelizumab, and have started a phase II study in both frontline and second line non-small cell lung cancer, as well as additional evidence generation in immune sensitive tumor types, including bladder, renal cell, and melanoma. HPK1, we believe, is a very important target. Our HPK1, which was one of the first HPK1s to enter the clinic, is advancing well through early evaluation. We have again identified a recommended phase II dose, both as monotherapy and in combination with tislelizumab, and have recently opened expansions in non-small cell lung cancer and esophageal cancer. Because we have seen activity with our HPK1 molecule, we think that this is a potentially important target in immuno-oncology. It turns out that we have a second HPK1 inhibitor that is on an entirely different chemical backbone.
We intend to bring that molecule into the clinic as well, so that we can compare safety, efficacy, and pharmacodynamic effects of the two molecules. From there, we have three new enemies that will be entering the clinic prior to the end of the year. Our CCR8, we believe, has best-in-class potential because it binds a unique epitope, which may facilitate more potent ADCC. DGKζ, like HPK1, is a kinase that sits downstream of the T cell receptor. This is a selective inhibitor of DGKζ and a potent activator of T and NK cells. Finally, PVRIG is another co-checkpoint monoclonal antibody that we believe has best-in-class potential, given its strong binding affinity and ligand blockade potency. The use of multi-cohort studies is core to our strategic and focused assessment of immuno-oncology combinations.
Umbrella trials evaluate similar treatment arms against the common reference arm with contemporaneous randomization to identify the most promising interventions. It really will allow us to establish prioritization across our relatively broad portfolio of immuno-oncology assets. They can be adaptive and allow for dropping ineffective interventions and flexible to allow new molecules to be added as they emerge from phase I. We have already initiated umbrella studies in advanced and resectable non-small cell lung cancer that are enrolling patients. We have an umbrella study in head and neck cancer that is in setup. To transition to what's next in solid tumor oncology at BeiGene, we are entering a transformative period with the application of new targets and novel methodologies across priority tumor types.
You'll hear from Lai in some detail about seven new molecules that we will bring into the clinic over the next 18 months for non-small cell lung cancer. On the lower left, from there, we are also bringing these novel methodologies and new targets across all of our priority tumor types. In the lower left, you can see in upper GI, we have both a bispecific antibody and ADC targeting CEA and a ADC, novel ADC targeting B7H3. In colorectal cancer, we again have the two CEA-targeting molecules, as well as a small molecule inhibitor of pan-KRAS. In head and neck cancer, our SMAC mimetic molecule continues to progress well through early investigation, and again, the B7H3 ADC. In breast cancer, we have recently announced an exclusive global option from Duality for their B7H4 ADC.
We think that this is a great target that's highly complementary to our internal portfolio of ADC targets. You heard from Mehrdad about the potency and selectivity of sonrotoclax, and we intend to test that in HRR-positive breast cancer. I'd like to spend a bit more time discussing in detail our selective inhibitor of CDK4. CDK4 inhibitors have had huge patient impact for women with breast cancer and have also been commercially very successful medicines. There are three approved CDK4/6 inhibitors, and all have dose-dependent toxicities that are related either to CDK6 inhibition or to other off-target effects. Although the adverse events with these molecules are driven primarily by inhibition of CDK6, efficacy is driven primarily by CDK4, and therefore, having a CDK4 selective molecule allows for improvement of both efficacy and safety.
There's a single CDK4 selective inhibitor that is already in the clinic that is being developed by Pfizer. That said, we believe that we have the potential best-in-class medicine, in that in a cellular proliferation assay, as you can see on the left-hand side of this slide, what you can see is that our CDK4 selective inhibitor has the highest potency against CDK4 of any of the approved CDK4/6 inhibitors or Pfizer's investigational CDK4 selective molecule. What this conveys is the greatest selectivity for CDK4 over CDK6, which we think will provide the widest therapeutic margin for us with this target. We have showed preclinical efficacy in a number of different preclinical models, and I'm very happy to say that this molecule has already completed its GLP toxicologic studies, did not have significant neutropenia or GI toxicities.
We are currently developing the IND and CTA submissions, and we'll have our first human dose by the end of this year. Putting it all together, across our target tumor types of upper GI, lung, head and neck, breast, and colorectal cancers, crossed against the diverse set of therapeutic modalities, we have developed a compelling group of innovative molecules to address priority tumor types. There is a large addressable population, an unmet medical need. Our B7H3 molecule, across multiple indications, CDK4 in breast cancer and potentially additional indications. The EGFR CDAC will be our first bivalent degrader in solid tumor oncology, the pan-KRAS molecule in thoracic and GI malignancies, and the MTA-cooperative PRMT5, again, in multiple solid tumors.
Therefore, we believe that we are well on track to establish Tisli as a global standard of care, to build the best-in-class combinations upon the foundation of tislelizumab with our next wave of immuno-oncology assets, and then finally, to expand into additional tumor types with novel agents, some of which have blockbuster potential. From there, I'm very happy to hand it back to Lai to share the exciting details of our innovative research programs.
I hope you enjoyed the presentation so far. BeiGene is developing a diverse and a compelling portfolio across hematology and the solid tumor, with 20+ programs in the development and the 60+ programs in discovery. I will detail our tumor type approach with the lung cancer portfolio where we have over 30 first-in-class or best-in-class programs, including CAR-T therapies, IO, and combinations. I will share with you seven new model programs that target lung cancer, including three small molecules, two ADC molecules, and the two bispecific antibodies, with differentiated TAA approaches. All these programs have compelling pre-clinical data. We're leading the industry in the breadth of novel modality designs. To improve patient outcomes, we combine differentiated targets with novel modalities across tumor types.
With our 1,100 innovative research team, we will deliver 10+ new medical entities per year to the clinic, starting from 2024. We believe we are on path to deliver innovation at scale. BeiGene pipeline has broad coverage in oncology with clear focus. Highlighted in red are our current key disease focus areas, including lung cancer and upper GI cancers in solid tumors, and the B-cell malignancies and AMR MDS in hematology. Pipeline grows, we are also expanding to few mature types, including head and neck, breast, colorectal cancers, and multiple myeloma. The following slides, I will take lung cancer as an example to walk you through our pipeline innovation strategy. Lung cancer presents about 20% of cancer worldwide, with high unmet medical need that we can address with our portfolio.
In the past decade, BeiGene has built a strong immuno-oncology pipeline centered around our PD-L1 antibody, tislelizumab, as shown on the right. Mark has given you updates on our progress in IO in his section. To complement the IO portfolio, we have also developed therapies targeting the oncogenic signaling pathways and the TAA immunotherapies. Today, I will discuss seven new molecules in detail. EGFR CDAC, pan-KRAS inhibitor, PRMT5 MT inhibitor, two ADCs, B7H3, and the CEA. Two immune cell engager, MUC1/ CD16 and Claudin-6/ CD3. For the color coding, dark blue stand for small molecule, light and lighter blue stand for ADCs and bispecifics, respectively. EGFR CDAC. EGFR mutations occurs in about 50% of lung adenocarcinoma in Asian and 15% in Caucasian, where it represents a very large lung cancer patient population.
Four generations of EGFR kinase inhibitors have been developed over the years. The first three generations are already on the market, the fourth generation are in the clinical development. EGFR CDAC induce complete EGFR protein degradation, which might present a better way to abolish EGFR signaling. By first, inducing more sustained signaling inhibition by eliminating the EGFR protein in the cells. Second, by covering broader EGFR mutation spectrum, by addressing both osimertinib sensitive and the resistant EGFR mutations. Third, by destroying EGFR scaffold function to minimize compensatory signaling via heterodimerization with other receptor tyrosine kinases. EGFR CDAC program is on track to enter clinic early next year. pan-KRAS inhibitor. Oh, actually, this one is the EGFR CDAC data.
As shown on the top right panel, compared to the traditional EGFR TKI, BeiGene's EGFR CDAC molecule has broader EGFR mutation coverage, targeting both osimertinib sensitive and the resistant mutations, yet it completely sparing wild-type EGFR. This molecule has demonstrated a very clean selective profile in the protein panel as well. The molecule has desirable oral bioavailability, which supporting daily dosing in the clinic, where robust antitumor activity was observed. Two models are shown on this slide. The one on the left is an osimertinib-resistant subcutaneous model, and the one on the right is an intracranial model. This molecule has good brain penetration. What is not shown here is that EGFR CDAC also works well in osimertinib-sensitive models. pan-KRAS inhibitor. As shown on the top right panel, compared to.
For the pan-KRAS, which is covers a very broad cancer population, which was found about in 15% of the all tumor types, pan-KRAS, KRAS has been a holy grail for the oncology. This is accounts for about 9% of the lung cancer adenocarcinoma in Asia and 33% in the Caucasian population. This also has high prevalence in the CRC as well as in the pancreatic cancers. The G12C KRAS inhibitor is the first success in the KRAS field. However, the G12C mutation only accounts for about 10% of the all KRAS mutations.
Although the KRAS knockout was embryonic lethal, we found in-house, the adult mice was inducible KRAS knockout appeared to be normal and healthy, suggesting there is a low risk with inhibiting wild-type KRAS by KRAS inhibitor. We believe this is due to the compensatory mechanism by NRAS and HRAS. We have developed a KRAS, pan-KRAS inhibitor, which is highly potent across different KRAS mutations and with good selectivity against NRAS and HRAS. PRMT5. PRMT5 is a protein arginine methyltransferase, essential to many cellular functions in both normal and the cancer cells. Many companies have attempted to develop a substrate or co-factor competitive PRMT5 inhibitor. However, the first generation of PRMT5 inhibitor cannot distinguish normal versus tumor cells. The development is largely impeded by unfavorable on-target hematological toxicity observed in the clinic.
To address this toxicity issue, we are leveraging a fascinating biology, a sensorimotor study concept, to develop the second generation PRMT5 inhibitor to selectively cure tumor cells with MTAP deletion. MTA is MTAP is MTA methylcell adenosine phosphatase. Tumor MTAP deletion leads to accumulation of MTA in cancer cells. MTA-cooperative PRMT5 inhibitor is designed to only stably bind to the PRMT5 in the presence of a high concentration MTA. Normal cells have very low MTA concentration, therefore, avoiding inhibition by the second generation PRMT5 inhibitor. MTAP deletion represents a large cancer population segment, finding about 15% of all tumor types, including lung and GI cancers. BeiGene's PRMT5 inhibitor has promising pharmacological properties with good brain penetration and a desirable half-life. Changing again, in addition to oncogenic target therapies, BeiGene has also developed a strong portfolio with TAA-derived therapies.
Hoxene ADCs and immune cell engagers are the current portfolio focus. I will highlight a few select programs from both platforms in the next few slides. Moving forward, we are also investing new ADC technology with next generation payloads and allogenic cell therapy with CAR-T against TAAs. BeiGene aims to develop innovative and world-leading ADC platform, with rationalized design to enhance efficacy and reduce toxicity. Our robust ADC discovery platform has enabled high quality and efficient delivery of single or multi-targeting antibody to fit different targets and disease biology. We also actively take various creative approach around payload linker conjugation to address the main pain points in the ADC field. For the payload, we generate a diversified and optimized payload toolbox to cover broader targets and indications. This includes propargyl topoisomerase I inhibitor, designed with better permeability to achieve stronger bystander killings.
We also have MMAE payloads paired with hydrophilic linkers to enable higher DAR. In addition, we leverage pro-drug design to enlarge safety window of PBD. For the linker, we use hydrophilic linker platform to improve ADC by physical properties and reduce aggregation, which is also equipped with multiple cleavage mechanism to support various drug design needs. For example, we designed a two-step lysosome cleavage tandem release linker to minimize systemic payload release. Another one is we screen the four linkers insensitive to neutrophil protease to reduce neutropenia toxicity commonly associated with MMAE payload. For the conjugation, we use stable conjugator and the site-specific conjugation technology to achieve homogeneous DAR and better ADC stability. BSMHC ADC is the first ADC product I want to introduce to you.
B7-H3 is highly expressed in various tumor types, including lung, GI, and gynecological cancers, as indicated on the top right table. DS-7300 is a B7-H3 developed by Daiichi Sankyo and has shown interesting clinical proof-of-concept data in small cell lung cancer and prostate cancer. Compared to DS-7300, BeiGene leverages internal ADC platform to pursue best-in-class opportunity via differentiated drug design, including higher bar, propargyl linker to enhance bystander effects, and a stable conjugator. I will show some data in the next slide. A detailed comparison versus DS-7300 is shown on this slide. In regards the medical design, BeiGene's B7-H3 ADC demonstrates stronger on-target and bystander killing activity, as shown on the top left two panels. In contrast to DS-7300, whose DAR reduced nearly 50% after four days post-dosing in monkey PK study, BeiGene's ADC shows good stability with sustained DAR over the time.
I would also like to point out, in xenograft models that are insensitive or resistant to DS-7300, BeiGene ADC still demonstrate robust anti-tumor activity, even at the half of the dose of the competitor molecule to compensate for the difference in DAR. Hopefully, this exciting data will also translate into better efficacy in the clinic. CEA ADC. CEA is a well-established TAA, highly expressed in lung and GI cancers, with tumor prevalence indicated on the top right table. Chemical POC has been achieved for Sanofi's SAR408701 in lung cancers. The overall response rate is only 20% in lung cancer patients with high CEA expression. While the activity is minimal in lung cancer patients with medium CEA expression, also was minimal in the CRC and gastric cancer patients. We believe there's a lot of room for improvement in the chemical efficacy.
BeiGene's CEA ADC adopts a highly differentiated ADC design, aiming to expanding target population to lung cancer patients with medium, low, high expression and GI cancer patients. Utilizing topoisomerase one inhibitor with high DAR to enhance the tumor killing versus DM4 anti-microtube payload, as well as the stable conjugated design and hydrophilic linker to enhance ADC stability and homogeneity. As shown on the left panel, BeiGene's ADC demonstrates prolonged vascular stability, while that for SAR408701 quickly dropped to only 20% remaining at the end of the PK study. While ADC concentration in tumor versus circulation was assessed, BeiGene molecule showed a higher tumor enrichment. In addition, BeiGene molecule was also superior in the bystander effect. Consistent with this great characteristics, BeiGene ADC also demonstrates robust anti-tumor activity in SAR408701-resistant primary colon and gastric cancer models.
MUC1 x CD16A. MUC1 is a very attractive TAA for multiple tumor types, especially for lung. Around 90% of lung adenocarcinoma has moderate to high MUC1 expression. To differentiate it from previously failed MUC1 monoclonal antibodies, BeiGene takes a unique MUC1 antibody discovery approach to target the membrane proximity region, which can minimize soluble MUC1 binding to avoid syncip effects, as shown on the top right panel. In-house bioinformatics analysis showed a nice correlation in the expression of MUC1 and CD16A, NK cell activating receptor. Based on this finding, CD16A NK engager was selected as a bispecific partner for the MUC1 program.
BeiGene's MUC1 x CD16A bispecific has the following characteristics: high CD16A binding affinity, Y-type FC function for FCR binding, and a spatial short distance between MUC1 and the CD16A . All these characteristics strengthen NK cell engagement, and they improve tumor cell killing. Claudin-6 CD3. Claudin-6 is a very clean TAA. It's highly tumor-specific, making the attractive TAA suitable for CD3 bispecific developments. Claudin-6 is expressed in lung and gynecological cancers. It is very challenging, actually, to develop a highly selective Claudin-6 antibody due to its close homology to the family member Claudin-9. There is only a single amino acid difference between these two proteins. Claudin-9 has broader normal tissue expression and therefore needs to be spared. BeiGene's Claudin-6 CD3 bispecific is highly specific against Claudin-9.
It is in fab single chain FV format to shorten the spatial distance between the two arms for better tumor cell killing. It can stimulate T-cell infiltration and result in robust anti-tumor activity in immune core tumors, as shown in the top right panel. In addition, it works in cells with low antigen levels and cures Claudin-6 negative cell via a bystander effect, leading to strong efficacy even in heterogeneous tumor models, as shown on the bottom right. I have shown you that we have a very deep target portfolio in lung cancer that complements well of our existing immuno-oncology pipeline. The seven programs highlighted today cover a very broad lung cancer patient segment. The target populations are distinct but also overlapping, which providing multiple approaches to treat lung cancer patients.
We have fully leveraged our integrated CMC and manufacturing capabilities across multiple modalities to empower a fast path to clinic. Over the last few years, we have also established an extensive early-stage clinical trial network. In addition, our internalized clinical development capability enables very quick clinical proof of concept, better than industry standard. I think everyone agreed that combination treatment is a key to the future success in oncology. With all these tools in our toolbox, we have tremendous flexibility and advantage to test the rationalized internal combinations. This slide is not meant for you to see the details, but rather give you a high-level view of the breadth and the depth of our BeiGene portfolio in our key tumor types of interest. Each column represents a tumor type, and each row represents a program sorted by modalities.
Over the years, BeiGene has heavily invested in various technology platforms and therapeutic modalities. Very few company has the breadth of the platform that BeiGene strive to build in-house. On medicinal chemistry side, we have shown you that we are able to produce not only one best-in-class molecule, protein stuff, but also potentially a second one, sonrotoclax. CDAC is in general difficult to make with good pharmacological properties due to its large molecule weight. BeiGene has one CDAC molecule, BTK CDAC, in the clinic, with beautiful proof of concept data that I showed you today, and that there are two more CDAC molecule at an early stage. One is EGFR CDAC, while the other one was undisclosed target. This makes BeiGene one of the companies with the largest pipeline in the protein decoration space.
One of our major efforts in the last few years is to upgrade our antibody discovery and engineering platform, which empower us to deliver complex antibody molecules with greater efficiency. On the ADC, we started running late, but now we have our own proprietary platform established with four programs at R&D stage and close to 10 in discovery stage. Cell therapies and mRNA therapies are still at a relatively early stage, with leading assets progressing on track towards clinic in the next couple of years. Hopefully, at the next R&D day, I'll be able to share with you more advancements in those areas. We're extremely excited about the next wave of innovation. In the next 18 months, we're on pace to deliver 15+ molecules into clinic.
What's exciting is not only the quantity, but also the quality of these molecules, hopefully bringing new treatment options to cancer patients around the globe. To summarize research innovation section, our 1,100 team in research is prolific and innovative. They run treatment-changing molecules at a pace of 10+ new molecules a year. We have kept our entrepreneurial culture and always have a sense of urgency, which we believe is extremely critical to our success. Our tumor type approach is comprehensive, including target therapy, IO, and combinations. The seven molecules we review today have compelling differentiated the lab versus competitive molecule or are in the leading position in their target class. We lead the industry in the breadth of novel modality designs. You have now seen how we strive to improve patient outcomes with differentiated targets and with novel modalities across the tumor types.
Finally, there are three take-home messages I hope you get from today's R&D presentation. First, BeiGene's hematology portfolio is more than just for cancer. Two other potential blockbuster medicine are being developed, sonrotoclax and the BTK CDAC, BGB-16673. Second, BeiGene's solid tumor portfolio is more than just IO. We have a broad target therapy portfolio with exciting new molecules to complement our IO portfolio. Third, research innovation at scale. BeiGene's research innovation is scientific and impactful and prolific. I will hand this back to John for his closing remarks.
Thanks so much, Lai. I hope everyone has taken away, as Lai said, the following points. You know, we do have one of the largest, most productive, and cost to time efficient teams in the industry. Our oncology clinical team is one of the largest and advanced in the industry today. It has a track record of success and again, sense of urgency and entrepreneurial spirit and focus on cost. The pipeline's impressive, 23 development programs, 60 discovery programs, two blockbusters already, two impressive programs that we think have now declared themselves and have tremendous prospects. We've already established a leadership position in hematology with three very important programs, and I think we've laid the foundation, as Lai showed you, to do the same in several other areas in solid tumors in the upcoming years.
I do want to reiterate our leadership position in Heme and our belief that this is not one program, it's really all three. I know you hear lots of noise from our competitors related to the BTKI space, but the data and the longer-term follow-up that was shared to you today with Merhdad, especially around the PFS separation in both the all comers and in the deletion 17p population, speaks for itself, and it can't be denied. Secondly, the BCL-2 inhibitor, Sonro. It is potentially best-in-class, superior safety and tolerability, but the ease of use should really be able to expand its use in the community setting. We're close to initiating phase III trials for the BCL-2, and the market potential here is quite large. Thirdly, our BTK CDAC.
It's exciting because it shows our capabilities in this important new platform, but also there's a clear and quick path for BTKI-resistant population. Given the removal of the structural function, it really has the potential to work in some of these other areas, like large B-cell lymphoma, Richter's, and potentially beyond hematology. Today, BeiGene's making significant progress on our path to oncology leadership. As we've said already, our medicines have treated more than 800,000 patients, and I think that's why we're all part of this industry, and it's why BeiGene's team is here and together. We have the entrepreneurial and the science-driven culture still. We've created this, it allows us to continue to make and work on developing critical medicines, and to make them quickly, affordably, and to bring them accessibly to more patients around the world. 13 years, it's been quite an adventure.
The industry and the sciences worked as we believed. You're hearing about covalent molecules, which people didn't believe in. You're hearing about immuno-oncology, which people didn't believe in. You've seen very impactful ADCs in this period, which people weren't so sure about. It's been a tremendous decade of impact for cancer patients. It's a tribute to the incredible, you know, partners we have in fighting cancer and peer companies that we work with and, you know, help develop science. It's amazing. That said, cancer is still killing 10 million people a year. No patient can face cancer alone. No oncologist can help patients alone. No family can deal with things alone. No company can fight cancer alone. No regulator, no policymaker.
We're all in this together, we're all trying to work together to move forward this ecosystem that we have to have impact, to try to fight and work to do our best to impact this 10 million number. We can only do it through working together as an industry, and we're really proud to be a part of that. That's what gets us excited every day and every morning when we wake up early and stay late, and makes us super passionate about what we're doing here. With that, I just want to thank everybody that works with BeiGene and that works at BeiGene, and all of our investors and supporters and everybody. Let's do our best to really have impact and help reach billions more patients affordably and reduce this 10 million number. With that, I thank you.
Thank you, John. In order to round out our presentations today, here is a summary of our upcoming catalysts in the H2 of 2023. We won't talk about them in greater details, but wanted to make sure that you have this information. With that, we are wrapping up our presentations and now moving on to the Q&A session. As our panelists come up onto the stage, I'd like to get out a few logistical items. If you have a question and you are in the room, please raise your hand and we will bring you a microphone. If you are online, please feel free to submit your questions on Zoom. When asking a question, please start with your name and your company before sharing the question. With that, let's open up the floor for questions.
Thank you very much. Yige Guo with Guggenheim Securities. Great presentation, and congrats on the progress across the R&D pipelines. I guess a couple of quick ones from us. number one, on the BCL-2 inhibitor, it's interesting to see that you guys are pursuing indications not pursued by venetoclax or not approved. In particular, multiple myeloma, can you talk about the frequency of the T-11;14 mutation? What's the opportunity? How big is the opportunity? Is it possible that, you know, the efficacy that we see in that population can be expanded to the total population? A second one on the KRAS and the pan-KRAS program. I guess there's a school of thoughts that inhibiting the wild type KRAS could sort of like contributing to the adaptive resistance.
I guess, but that could come with some on-target toxicities such as rash. Wondering, what's your thoughts on, you know, balancing, the inhibiting the wild type KRAS, but dialing out the on target toxicities? Thank you very much.
I'll start with the BCL-2 inhibitor in multiple myeloma with translocation 11; 14. Translocation 11; 14 is about 20%-25% of the overall population. Thankfully, as physicians are learning about this translocation, a vast majority of multiple myeloma physicians or even community physicians are testing for 11; 14. Like I said, the pie is huge. That's why 25% of this pie will remain huge as well. We are taking several paths to that. Actually, we are starting with some of the indications that venetoclax has not approved, but of course, we are pursuing all of those, including CLL and AML.
I can take the pan-KRAS question. Now, as you pointed out, because KRAS is such an essential molecule for the body, there was a lot of concern about developing a pan-KRAS inhibitor. We actually did not just initiate program based on a scientific hypothesis. We actually did experiments. We made a KRAS conditional knockout mice, and we did a adulthood whole body systematic knockout, and the mouse was perfectly fine. With that piece of data, you know, previously people only did for the bone marrow kind of specific knockout. With that data, we should went on to start the pan- KRAS inhibitor program because the pan- KRAS inhibitor will inhibit wild type KRAS.
We believe in normal cells, the signaling pathway will be compensated by NRAS and HRAS, therefore, you shouldn't be in the major toxicities. So far, our molecule we have made in-house has been very well tolerated in the animal models, so this remains to be seen in the clinic, but we are pretty confident there shouldn't be a major issue with the pan- KRAS.
Thank you. Next question, please.
Sam Issibavy, XL Asset Management. Congratulations on a marvelous outlook at a micro level. I have a question for you. Some five years ago, maybe more or maybe less, a Senior Chinese Official, maybe Xi Jinping, I'm not sure, was very proud to point out that the PD-1 prices in China were the lowest in the world. How can this be good? Can you specify what I'm trying to remember? What's your outlook for pricing on a longer-term outlook in China?
Sure, sure. I don't know exactly to what you're referring, but I can certainly speak about pricing. You know, with the largest number of cancer patients in the world, 25% of all cancer incidents are in China. I think as we built this company, we understood that, you know, if you charged U.S. pricing in that country, you simply can't afford it. The GDP per capita is much lower. From that perspective, our expectations in building the company was you'd have a range of prices under reimbursement that would range from roughly several thousand dollars, probably on average $2,000 a month, and that's all that could be afforded at this point in time. Nonetheless, if you looked at that and saw reimbursement, you'd be in a situation where the industry would contribute billions of dollars back to innovative medicine.
I think as we've laid out, most of the cost for innovative medicine is upfront. It's in clinical trials. I think today there's about $17 billion in oncology that's coming back to the industry to pay for that upfront cost of clinical trials from China today. The price point is roughly where we assumed it would be couple thousand dollars. This is different than in the U.S. and I think we have a, you know, system in the U.S. where pricing has been very high. Medicine, I think as I said, when the company was started, really innovative medicine was only getting to 1/6 of the world. Our approach as BeiGene is, first of all, we have to dramatically reduce the clinical cost, which is upfront.
If this is 75%-90% of the total cost of making a medicine and delivering it to a patient, you know, how do you do that? You do it, first of all, through getting to additional centers and bringing them into the clinical trial, you know, pool. We've done this in Australia. We're doing a lot of work in Poland and Italy, now in Brazil and South Africa. By getting to more centers around the world and in the United States, working with centers that are often neglected here, we're able to, you know, conduct clinical trials more quickly and conduct clinical trials more cost-effectively. Our goal is through globalization, through adding additional centers, through internalization, not using CROs, and through adopting the latest technology. Almost all clinical medicine now is double entry, manual double entry to get into a clinical trial system.
You know, working to fix these things, our aspiration is to reduce clinical trial cost in half. I think we're 30%, not 50% so far. I think the second part is, once we get a medicine approved, because we've become so good at manufacturing in our industry, whether it's a small molecule or a biologic, our cost of goods sold is now dramatically lower than it's previously been. I think our ability to now take those medicines and try to get them to more places around the world, even if it's a lower price point, as long as they're contributing above your cost of goods sold, creating a gross margin, which can come back and help pay for that upfront cost of the clinical trials.
Both BRUKINSA and Tisli, you know, ultimately, you know, we've probably spent close to $1 billion on those clinical development programs. The revenue that comes back from these other places, even if it's at a lower price, it can help us cover that upfront cost, which in our minds can ultimately lead to lower pricing here in the United States, and in Europe, and in Japan, the traditional markets. To that effect, you've heard of, you know, the BTK, superior on efficacy and superior on safety. Yet in the United States, when that product is launched, it's selling several thousand dollars a month less expensively than ibrutinib. Why is it doing that? That's our philosophy and because we believe that.
Can and are generating revenue across the rest of the world that can help us support a model and demonstrate a model that will result in lower pricing here over time. That's really what we're trying to drive to. You know, we think it's actually, you know, working quite well. We hope to prove that with BRUKINSA globally as we get to the CFDA markets, and we hope to prove that with Tisli as we bring it to the rest of the world, too. Thank you.
Thank you. Thank you. Next question, please.
Hi, thank you. Yigal?
Yeah.
Hi, Yigal Nochomovitz from Citi. Great, great presentation. Very, very interesting. I have another strategic question. It does intersect with Sam's question on pricing. This with regard to the combo with sonrotoclax and BRUKINSA. Excellent new phase II data with the efficacy that you reported, as well as favorable safety. My question was related to thoughts in terms of doing the combo in first-line CLL until progression, or at least a much longer epoch effect, fixed duration in the broader CLL population. What are your thoughts about that? The reason I ask is given the IRA likely having an impact on the pricing for the BTK class towards the end of the decade.
If you had a combo option, that you could, match, BRUKINSA with in the first-line population, that would give you another way to potentially protect BRUKINSA price, later in the decade. If you could comment on that strategically, and clinically. Thank you.
Maybe I should start from the clinical standpoint, if you don't mind. Like I mentioned, the real emphasis that we see from physicians and patients and all is a fixed duration of treatment, and that's as short as possible, because patients want to get a treatment and be done. Similarly, particularly post-COVID, we know that everybody wants a short treatment and not going back to clinics. Based on everything that we have seen in CLL field, including the venetoclax obinutuzumab that I showed, one year seems to be an optimal period, and that's why we have been anchoring our MRD negativity and our CR in that one year. We think with one year of BRUKINSA plus sonrotoclax, we'll put a lot of patients in MRD negativity and a long outcome. Not every patient will go on fixed duration.
It actually depends on patient's desire, physician's desire, subset of CLL they have. A few, some of our patients will remain on BRUKINSA up to progression, but some patients will prefer to go on the limited time treatment. There are a lot of effort just outside us as well. Like I said, you know, venetoclax obinutuzumab is a good regimen, we'll get those patients. There are patients who are currently getting ibrutinib plus venetoclax, we'll get those patients as well. That's how we see fixed duration as something that physicians want, that's how we see we're going to capture those patients. I think in terms of the strategy and what it means for pricing and all that, I'll defer that to my colleagues.
Thanks. Mehrdad, Just to make sure that I'm tracking, can you ask the second part of the, of the question again? Yeah.
Just I mean, there's going to be pressure on the BTK class, given IRA, presumably, and that may trickle through to the more innovative products like BRUKINSA. If you can pair BRUKINSA with a novel mechanism and price that as a duo, potentially you can protect price given claims around efficacy that you wouldn't have with the monotherapy. Is that a strategy potentially to expand that duo beyond just a fixed duration into the broader frontline population and treat to progression to capture that dynamic?
Sure. Thanks, for the thoughtful question. If we take a step back and we think about the impacts of IRA, right? It's on the molecule level. You know, the potential impact for zanubrutinib would happen irrespective of, you know, sonrotoclax.
Right.
I think if your question is, if the price, you know, comes down through the obligatory discount, you know, then by pairing it with sonrotoclax, we have a chance to perhaps provide more value through the combination. I think that's accurate. Really, what's going to be the clinical data that'll, you know, set the strategy. Other thoughts potentially around how we might package them together, in other ways that we might come to market. We're still need to evaluate that and see how the landscape changes over time. At the heart of your question is like, does this potentially unlock more value for zanubrutinib generally? Through the combination, I would agree with that.
I think the other aspect of the combination that might be a bit underappreciated is right now, you know, venetoclax is primarily paired with obinutuzumab from a fixed duration standpoint. So that's VO. Ibrutinib plus venetoclax, if you look at the U.S. market, a very low utilization, right? It's not currently approved. Actually, the sonrotoclax zanubrutinib combination as a potential opportunity to grow the BTK class, right? There's been some questions around potential cannibalization of zanubrutinib monotherapy. I think it's important to think about the reason patients get combination therapy, the reason they might get fixed duration. It's different from getting a monotherapy approach.
We would anticipate, you know, less cannibalization of zanubrutinib monotherapy and actually a growth of the zanubrutinib opportunity through erosion of venetoclax and obinutuzumab, and potentially then going into the other aspects of the market that are still getting chemo immunotherapy, right? Because the goal there is a deep and fast response. That's not why you use a BTKI monotherapy. In addition to your question, I think there's also the potential for sonrotoclax zanubrutinib to grow the overall market for BTK inhibitors and to grow the opportunity for zanubrutinib as well.
Thank you.
Sure.
Thank you. Next question, please.
Hey, this is Ken from Merion Partners, from speaking on behalf of Andy Barons. For the PRMT5, MTA cooperative program, wondering if, you could speak to any potential differentiation from other competitors from the second generation class? I mean, we've seen compounds from Mirati, Tango Therapeutics, I think, had initial data. I think Amgen has a program as well. Maybe you could speak to potential differentiation for that class. Thanks.
There are still very limited information out there for the other second generation PRMT5 inhibitor, as you point out, including Mirati, Amgen, as well as Tango. We have done some in-house analysis versus those competitor molecules. I can tell you, a lot of work is still ongoing. What I can say is about our molecule, which has really good pharmacological properties, and all about availability, we test out the competitor molecule, none of them are that great. You know, in terms of dosing-wise, it probably requires like twice daily dosing, as well as the brain penetration, we believe, is a very important characteristics for treating lung cancer patients. Our molecule has all those characteristics. Ultimately, you have to do the experiment in the clinic to see whether they are truly differentiating or not.
At this moment, I think this will be a highly competitive field. Don't get me wrong, a lot of people is investing that. you know, it's still very early in the game. We believe we're right out of game, and probably have a chance to take a leading position once our molecule gets to clinic.
Next question. Can we go to online? Lisa, can you please read the question that we are getting? Thank you.
One of the questions was asking about the timing for tislelizumab approval in the U.S.
That remains open-ended. We have, as I mentioned, we've completed the on-site GMP manufacturing inspections, and at this point, the, shall we say, the ball is in FDA's court in terms of the final adjudication and hopefully completion of the review period and determination of benefit, risk.
I'll ask another, that was submitted online. is asking about the Novartis agreement on TIGIT and what's next for the program.
Again, as I mentioned, we acknowledge that the external data flow has been mixed related to TIGIT. Ultimately, that's a question for Novartis. We don't have visibility to their internal discussions and deliberations in regards to specific programs. As I mentioned, we're very happy to have TIGIT back. We have broad development program of phase two studies, which, as John has mentioned, we have delivered at very favorable cost. It'll help us to understand what's the opportunity landscape for TIGIT as a class, and we carry on and are optimistic about our study in PO1 high frontline non-small cell lung cancer.
Thank you. Next question. Let's come back to the room.
Great.
Thank you. Kelly Shi from Jefferies, and a fantastic presentation and a lot of interesting development. I have two questions regarding the pipeline development. BeiGene recently signed a deal with a Shanghai-based ADC company, I think DualityBio , for two early-stage ADC assets. Could you share what kind of ADC technologies attract you to form this strategic partnership? How does it synergize with the internal ADC development effort?
Yeah, I can take that question. We actually did one licensing deal with Duality, which is option deal. In a way, we want to take over the program at a clinical stage this year, during the preclinical development. In terms of the reason we did that deal with Duality is we look at their platform first. Only to the extent I can disclose, it's also topoisomerase inhibitor-based platforms. We look at the preclinical data package, we believe is highly competitive. Also the targets, as Mark mentioned in his presentation, is B7H4, which complements extremely well to our current, you know, evolving breast cancer portfolio. This is really the rationale behind we did the deal with Duality. This molecule will be in the clinic early next year.
Thank you. The BTK degrader looks very promising and very critical for our franchise building. I'm curious if you also see a very autoimmune indications for this molecule besides the development plan you laid out in oncology?
A very good question. Certainly BTK as a class, has shown some promising activity in the autoimmune disease, including the multiple sclerosis, et cetera. You know, at this moment, are developing the zanubrutinib in the autoimmune disease, with several different trials ongoing. In terms of the CDAC side of it, certainly we do believe has a chance for the autoimmune disease. The question is which indication, and at this moment, we're still contemplating that strategy internally.
Great. Lastly, if I may, is a high-level question. Given the very broad programs with both high-profile targets and /or novel modalities for developing next wave of oncology drugs out of BeiGene, and also very promising data you presented today from multiple fronts, such as BCL-2 inhibitor and the BTK degrader.
Can you help us to understand how do you strategically plan the pipeline development, with the considerations of efficiency, cost, and maximizing the opportunities? Thank you.
I love that question. For our industry, as in the world, the most difficult part is to predict which target will be successful. If you look at our industry as a whole, in the past 20 years alone, you can see we didn't do a good job in terms of predicting which target is successful. By using PD-1 versus CTLA-4 as an example, CTLA-4 looks much better than a PD-1 preclinical model. BTK versus PI3 delta is another good example. They both work in B-cell malignancy, but one become really a multi-billion blockbusters drug, another one really at this moment, has a very minimum commercial market. BeiGene has a belief we have to be focused in terms of our disease, our interest.
In that particular disease, our interest, we're gonna do multiple shots on goal. The shots we are making are really based on scientific rationale, based on the impact which we predict this drug potentially have, but not necessarily make a decision in the beginning and say, This one will win, that one will lose, because it's really difficult to predict until you have a clinical proof concept data. So we also spend a lot of effort trying to thrive in this process from preclinical candidates to proof concept. If you look at the entire development cost for a drug, from the target all the way to clinical proof concept, probably accounts about 1/3 of the overall drug development, while the phase IIIs, the late-stage studies, usually comes for other 2/3.
If you really do well in the first part, to give yourself the chance to see the clinical proof concept, you're really in a much better position to make the ultimate decision. We also believe in our industry, the place you can really do much better job in prediction is when you see the clinical proof concept. In to, you know, to summarize what I'm saying here is, we're really trying to thrive from the target all the way to the proof concept. At that stage, you know, we're also trying to really focus on our disease area to make very good shots on goal, and then ultimately make a decision based on the clinical proof concept data.
Thank you, Lai. We have time for one more question.
Hi, this is Steve from Morgan Stanley. Thanks for your presentation. I have two questions. The first one, can you talk about, for example, when you BTK CDAC , can you compare the advantage versus non-covalent BTK inhibitor from Eli Lilly, for example? The second one is, for example, I want to follow up on the t( 11; 14) transformation in multiple myeloma. Could you remind us the treatment efficacy of the current therapies in this subgroup of multiple myeloma? Thank you.
I'll summarize what we saw in our BTK CDAC. We have had patients who are heavily pretreated. A majority of them, for diseases that do get covalent, have gotten covalent. Some of them had BCL-2, and some of them even had non-covalent or pirtobrutinib, yet we saw the responses. From the efficacy standpoint, again, the numbers are small. We think the efficacy is on par with what pirtobrutinib has. From the safety standpoint, our database is small, but we are very happy with how the safety is coming together. We do foresee a future, if everything holds, then non-covalent inhibitor actually is gonna be irrelevant, because for now, frontline treatment is with covalent BTKs.
If we know that regardless of all these mutations, because all the covalent and non-covalent BTKs, there are some evolution of mutations that are coming, so then everybody can go on a degrader. They can be more potent because of the way that we described them, that the mode of action is. The future will tell, but that's what we are hoping for, and that's what we are aspiring for. In terms of translocation 11; 14, it's a, like I said, it's a test that all physicians are doing. There are no approvals for translocation 11; 14 yet. However, venetoclax is available to patients. Most of the patients are being treated same as any other multiple myeloma, say, with a triplet or even quad, and then they cycle through all the available treatments.
Because venetoclax is available, some physicians are using that. Remember, the first trial that was done in this subset was a combination of bortezomib plus venetoclax, and that trial unfortunately failed because of increased toxicity. There was increased death and a lot of increased toxicity. When you look at just progression-free survival, the progression-free survival in 11;14 was amazing compared to just bortezomib. That's why we think because our drug is safer, because we are trying to do it, you know, with dexamethasone first and with carfilzomib, that has a different toxicity profile, we're able to produce the data that's going to be more superior. Venetoclax does have a study, I don't know why the outcome is really, you know, delayed. We'll see when that comes out.
We are concluding today's Q&A session. I'd like to thank all of our investors and analysts for your interest in and support to BeiGene. I also would like to thank the entire BeiGene team for their support to this event. I wish you a good day or good evening, and we look forward to seeing you again soon.