BeOne Medicines AG (ONC) Earnings Call Transcript & Summary

Great. Good afternoon, everyone. My name is Jess Fye. I'm a senior biotech analyst at JPMorgan, and we're continuing the conference today with BeiGene. The presentation is going to start with the company's Co-Founder and CEO, John Oyler and then we're going to move right into Q&A after that. [Operator Instructions] But with that out of the way, let me turn it over to BeiGene's Co-Founder and CEO, John Oyler.

Thank you so much. It's a pleasure to be here again. I think I've been coming for 13 years. And for the first year, BeiGene was really focused on research and development. I think we quickly developed and showed our capabilities in that area. And along the way, we've generated about $6 billion in revenue or collaboration revenue. And all of that, we've chosen to reinvest back into BeiGene in an effort to build internally a really advantaged cost advantage and time advantaged set of infrastructure. And to do that so that we could be as impactful as we could and become an oncology powerhouse company. I'm really excited to share with you the new chapter of the story as we move forward today. Of course, I have to share with you these disclosures, please read this very quickly. As a company, I think we're pretty unlike most of the other organizations here. We're very complex, and we're hard to understand. And in this presentation, I really want to share only 3 simple thoughts. First, that we're built very differently. We've been built globally from the beginning, and we've been built to have strategic cost and time advantages. We're already an innovative oncology leader in hematology, and I think we're rapidly becoming and hopefully, a year from now, I can show you that we're a leader in the solid tumor area. And we have one of the largest oncology R&D teams and one of the most compelling pipelines in the industry already. And I think next year, we will have transformed into a very different company than we are today, a clear leader, and we'll have clarified our path to cash flow positive and profitability and the strategic advantages we have. So let me start with the environment in which we're built and why we've invested to build innovation with cost and time advantages. I think we all know that science is making a huge impact on cancer patients. This slide shows the dramatic improvements in 5-year survival over time for most cancers. But there's still much to do when you look at areas like esophageal cancer, lung cancer, liver cancer and pancreatic. I also want to point out that the impact has come from many new modalities that were viewed with great skepticism and viewed as unproven when BeiGene was started just 13 years ago. These are now proven modalities and they're highly impactful, and they're giving us all many, many more tools to fight cancer. These modalities are still in their nascent stages, and they're going to continue to mature and have profound impact on patients and will help us address these areas of unmet medical need. Most innovative medicines are only developed today to the wealthiest 1/6 of the world. This is where we're falling down on our job. Almost 1 in 4 Americans have difficulty affording their co-payments for treatments and medicines typically don't get to most of the rest of the world until there's patent expiry. Most healthcare systems are really straining to reimburse these impactful medicines. So when BeiGene set out, this is the environment we were in, we wanted to change the cost structure. In looking at the industry, we saw clinical costs have skyrocketed. When we started the company, there were about 150 per patient fully enrolled. Now they're nearly twice as much. We also are seeing enrollment delays as one of the largest concerns of the industry. I think many of the pharma CEO have talked about this in their R&D days. Clinical costs now make up 75% of the total cost of delivering medicine to a patient. It's not the research, it's not the manufacturing, it's the clinical cost. And the traditional centers are full. They become strained, they become expensive. And developed medicine affordably and quickly, it really required a dramatically different, more global approach to clinical trials. And on this slide, you can see the differences in cost. This is just investigator fees and running trials in different places. So the goal for our company as we started it was how do you access this? So why are we unique? How did this shape BeiGene growing up in an environment? We wanted to address affordability and ensure that you could build a sustainable, profitable company in an increasingly price-challenged world. That's where we're landing. We focused on redesigning the entire approach to clinical trials through doing 3 things. We broadened our local and global inclusion by going to centers where CROs and major players were much less present. We built a CRO free internal clinical team. It's now over 3,000 people. And we developed enabling technology that ensured quality, lower cost and that we could operate as efficiently as possible. At the same time, although this is the biggest element of cost, we also invested in building our own research and manufacturing to reduce our costs there. And this not only reduces your cost in manufacturing for cost of goods sold at the end of the day, increasing your gross margin, but it can reduce the cost of a clinical program by tens of millions of dollars. So where are we against this vision? In the first 3 quarters of 2023, we generated $1.8 billion in revenue. That's a 76% increase over the previous year. We have 17 approved products and $3.2 billion in cash at the end of Q3. The clinical development team is not only 3,000 strong and global and CRO free, but the teams enrolled 22,000 patients and 125 clinical trials in 45 countries and regions. And the overall team's 10,000 people and strong. We have global scaled manufacturing of our own for biologics, for ADCs and for small molecule drugs, and we're really excited to bring online in the first half of this year, our new facility in Princeton, New Jersey. And we have one of the largest pipelines with over 50 potential oncology medicines. I'll share more about that later. And the model is working. We've already shown we can reduce our clinical cost by 30% and increase the timing of enrollment by 30%, and we think there's lots more room for improvement. Our global scale is setting us apart. In the past 7 years, BeiGene has completed more Phase 3 oncology trials than Novartis, twice as many as J&J and 3x as many as AbbVie or Amgen. This model has enabled us to vastly rise to a top position in global oncology leadership. We're already a top 10 in rising in global revenue in heme. We're one of the top 5 companies, as I said, in completing Phase 3 oncology trials since 2017. Top 5 for oncology molecules advanced into the clinic in the same time period. We have one of the largest research teams in the industry. That's all research. 1,100 entrepreneurial research scientists trying to put new compounds into the clinics. And we're just beginning to see the fruits of these labors. So second point, BeiGene has become a leading oncology innovator. We have a proven track record and a compelling portfolio across both heme and solid tumors. In heme, we're already a leader. If you were at ASH, you know that. We're building leadership in solid tumors with a very compelling early pipeline, we're going to talk about a bit today. And we have one of the most compelling overall oncology pipelines with 50 potential medicines. So let me talk about heme. I want to discuss a few reasons. We have to start with BRUKINSA. BRUKINSA is the best-in-class BTK inhibitor. It has the broadest label in the class, and it's differentiated on efficacy and safety. This is competing in a market with $15 billion estimated in potential revenue. And we're really poised to succeed here. The second molecule that's listed on this is Sonro. Sonro is our BCL-2, it's a very similar story to BRUKINSA. We think it's a better molecule preclinically. It's now seen over 600 patients in the clinic because of its PK characteristics, a shorter half-life and its potency and selectivity, we think it can go places venetoclax does not. From that perspective, not only is it helpful in the indications we're in, in lymphoma, but it also opens up some new indications we haven't been in. This is estimated at $4 billion for venetoclax market today, but if we can take it where we think it is, it could be an even bigger market. The third asset on this is our BTK degrader. This is a perfect example of what our clinical infrastructure could do. We were second in the clinic with a degrader in the space. We love the data that we presented at ASH, but we now have 140 patients enrolled on this. I think the lead compound to enter the clinic has a small fraction of that. This shows how quickly and cost effectively, we can move. And the data from this is very compelling. Again, because it takes out the structural function of the protein and is not as subject to the same resistance mechanisms, this probably has the ability for fast approval and cleanup of resistance and then potentially even to go in places or for longer duration than a covalent BTK inhibitor. And lastly, TEVIMBRA, TEVIMBRA at ASH had very nice data concurrently published in Nature Medicine around Richter's transformation in combination with BRUKINSA. This is really exciting because Richter's is the worst thing you can hear if you have CLL. And there's a very good response rate from that perspective. So again, BRUKINSA, it's a great asset, best-in-class BTK. I will just point out the things that are bolded here because I think you know a lot about our BTK. The first point that I want to make is we have shown sustainably after another year's follow-up that we had the separation, we're the only BTK inhibitor that is shown in a clinical trial that it is superior to IMBRUVICA. We'll talk about that in a second. We also -- if you look across the cat class and the different responses you see, we see response rates, CR rates and PFS that looks different than the other BTKs. On toxicity, we have minimal treatment-related things versus the other inhibitors in the class, including acalabrutinib on infection, on AFib and on severe headache, cough fatigue. This is great data. We're very excited about it. In addition to that, we're approved in 5 indications. That's more than any other BTK. Of course, the marquee data from that is our 1-year follow-up presented at ASH. This shows the sustainable inhibition. Again, if you look on the right-hand side of this, you see the deletion 17p, P53 population. This is where acalabrutinib ran a trial in the same population. It had a hazard ratio of 1, meaning no difference. Our hazard ratio is 0.52. The data absolutely speaks for itself. Sonro, again, best-in-class on efficacy, better safety and convenience profile that can take in other places, multiple registration opportunities. It also opens up new indications that we haven't been in that we can get to moving forward. The degrader, this is the first time at ASH I had KOLs not asked me if I could sponsor an IST, but if I could instead get them medicine, get them drug, get them on the study, get them a [indiscernible] in the study. People are really excited about this. The efficacy is looking good from an early perspective. We hope that hurdles up. The safety profile to date is very good, but again, it's very early. But there's 140 patients on this fast path to approval and then potential in big indications. And this is the data that I mentioned from Nature Medicine and Richter's very impressive. It certainly was fun to be at ASH this year. I think we've cemented BRUKINSA as the best-in-class in CLL preferred option, superior data, broadest label. I think with Sonrotoclax, there's a lot of excitement, same with the degrader and we're expanding our footprint into these new indications, AML, MDS, multiple myeloma. And the BTK CDAC because there is the potential to remove the structural function, perhaps has opportunities in Richter's in large B-cell lymphoma. So let me switch to solid tumors for a second. Of course, we have to mention TEVIMBRA. TEVIMBRA is growing, from a revenue contribution perspective, through its expansion in China, it's now approved in the EU and it's pending approval in the U.S. The EU approval opens it up to the rest of the globe, and we're excited about that. And there's actually a lot of combination work going on that could give it a unique position in the industry. Secondly, we're advancing, as I said, one of the most exciting early solid tumor portfolios in the industry. And third, we have this broad 50-plus clinical assets with multiple decision points reading out. So TEVIMBRA, what's worth mentioning, TEVIMBRA is treated more than 750,000 patients. We did over $144 million with it in the third quarter for revenue. There's a lot of positive data set, and this is just beginning to get out to market. And of course, from a cost perspective, we talked about reducing manufacturing costs as we've scaled up and brought this in-house, we're able to dramatically reduce the manufacturing costs. So early pipeline. This is like picking your children. There are seven assets here, but we're actually putting many more in the clinic this year. So this is seven I want to talk about. They're each very compelling on their own right. You may be familiar with some of the targets, but each one of these, we think, has a very, very big opportunity. I'm going to break out the three with stars and talk a little bit about them, but the ones without stars are in an appendix, which can be found later online. So let me start with the CDK4. I think we all know the CDK4/6 space is a very big market. It's been important, and it's had huge impact in breast cancer. The problem has been tox associated with things. And from that perspective, we've been able to develop a CDK4 inhibitor that spares CDK6. If you look in the top chart on the right hand, you can see our potency. On gray bars, you can see the 3 approved CDK4/6s. If you look at the light blue bar, that is Pfizer's just starting Phase 3, the main compound competitor for us in the space and you can see that we're 4.3x more potent. You can also see on the bottom that we're more selective. We're really excited about this and the low affinity for CDK6 leads to less hematology TOX, and this also has good brain penetration. The second asset I wanted to talk about is the EGFR CDAC, we all know this space well. If you look at the top, you can see what BeiGene is inhibiting. It's every possible EGFR, you want to inhibit while it's sparing in the wild type. You can see below that, the 2 AstraZeneca products, both excellent products, what they're hitting and what they're not and that they don't spare the wild type. And you can see the not yet a blueprint asset right below that. We're really excited about this moving into the clinic. We hope that it can be even half as exciting as our BTK degrader is once we get some data associated with it. The next asset I want to highlight is the FGFR2b ADC. So this is a differentiated modality to pursue a best-in-class opportunity. And I think that in this space, the lead asset is a single monoclonal antibody from Amgen, which has shown great data. and gastric cancer. The issue associated with it is there's a substantial portion of the patients who have severe ocular toxicity. In the bottom right, you can see the data we have showing that we're able to spare that. And we believe with an ADC approach, we can hopefully see better efficacy. This is going into the clinic shortly with the platform technology we have, which we think is state-of-the-art from an ADC perspective, and will be manufactured ultimately through our ADC facility that is online at this point. This is just making the point, that's not all we have. There's a lot going on in the company. There's a lot of data readouts. We'll talk about that a little bit later. And we're very active across a broad range of types of tumors and across the board, many, many modalities being applied to these. We do think we're a real leader in protein degradation, and we hope to show the same within a year from an ADC perspective. So with that said, I want to jump to the last section and talk about how exciting and transformational we think this year is. I think, hopefully, I've shown that we built a very different company. It's scale, it's global nature, it's capabilities, it's focus on cost and speed does not look like many other biotechs at the conference. We have a unique competitive advantages, as I've said, on speed and cost, and we have a track record of innovation. We've really built these capabilities. It's not easy. It's required significant investment and a truly global mindset. And it takes a little bit of time when you plant those seeds for the trees to grow for the fruit to sprout and then you can bear the fruits of your efforts. I think now we're on a clear path towards transitioning our company from cash consuming to cash generating, and I know investors love to hear that. And with this foundation in place, we think we're really on the way to becoming a global oncology leader. I would like to spend a moment though and talk about some misperceptions which we believe exist related to BeiGene. We're complex. We're hard to understand. We have no real biotech peers when you look at the size and scope and what we're trying to do. We've invested heavily to become a leader. We're doing great with internal innovation. We have our cost and speed advantages, but we have not provided guidance to investors. And I'd just like to take a moment to talk about a few of these things. Let me start, if I can, with geopolitics. I think a lot of people fear bifurcation in the world, since the first revenue for BeiGene came from China, our stock moves with China-related news. In fact, in Q3, nearly 2/3 of BeiGene's revenue came from the U.S. and Europe, and that percentage is ever increasing. Given the higher pricing, it's even a higher percentage of our gross margin that comes from these markets. I would like to reiterate that our IP is global and held in a manner that all 50 clinical programs and a dozen more preclinical programs would not be impacted by any geopolitical issues. Our primary competitive advantage is our global clinical trial infrastructure across dozens of countries. And this continues to function and provide its cost and timing advantages. In fact, BRUKINSA, the development of BRUKINSA, 90% of the patients roughly were enrolled outside of China. Lastly, the supply chain is well diversified as all companies should be with large safety stock and global manufacturing. The second misperception about our company is around our cost structure and that it is high, which is really saying that BeiGene spends too much money and has no clear path to profitability. Well, I think it's true that our R&D spend is at the top of the industry. It's because our research team is one of the largest and most productive and our oncology pipeline is one of the most compelling in the entire industry. I would like to say when we spend money on R&D or manufacturing, we have meaningful cost and time advantages. And in these areas, as with commercial, as you build out the market, it takes time to see the fruits of your labor and you're about to see those. So yes, we've invested and we built differentiated capabilities, but now you're going to see, as our revenue rapidly grows, driven by BRUKINSA and other medicines that we're going to be one of the fastest revenue growing companies with moderate expense growth. I'm sorry, I skipped my point. So the other concern is around single asset. A lot of people say, look, companies they get their first asset, their stock. They can never bring the second one to market. How does that work with BeiGene? How are you going to do it? Well, those are companies that are much smaller, that don't have the team size we have that don't have a 13-year history that don't have 50 assets in their clinical pipeline that aren't spending in one of the highest levels in R&D in oncology. I think from this perspective, the heme data at ASH stands for it speaks for itself. Look at what we're putting in the clinic really think this one through. Because I think when you look at the weight we're punching out as an R&D organization, it's a pharmaceutical company. And I don't think people are asking, is Roche going to be able to make another successful oncology medicine. We're miles from Roche, but I don't think we're like a small biotech company with its first approved product. It's just not the right comparison. The last issue for us is litigation. And I would like to state very clearly, we have strong IP in everything we do. We're big believers in science. We're big believers in IP. We have filed in this extra judiciary process to overthrow a patent that we think was overreaching. It's all public. You can read why we believe that to be the case. Please go do so if you have any concerns from this perspective. So where are we? We've built a foundation for significant growth and financial inflection point. How have we done it? BRUKINSA and our other products are driving revenue growth. As we have discussed, we have differentiated capabilities. Our costs are now normalized and our operating leverage is increasing rapidly with the revenue growth from here, and you're going to see continued operating margin over time. And moving forward, I think you're going to see our expanding assets and core approvals and new indications and reimbursements in new markets from that perspective. So now let me share the real numbers. What do they say? This is what matters. On the left, you can see the rapid growth of our global product revenue to $595 million in Q3. Our 1-year and 3-year revenue growth rates are 70% and 87%, respectively. In the middle, you can see as our business matures, nearly 2/3 of our revenue is already coming from the U.S. and EU, and we've really not brought on Japan and the rest of the world yet. So we expect this mix to increasingly reflect the global nature of our business. And on the right, you can see our product mix for the 17 not 1 product that we have on the market. We're really pleased with TEVIMBRA, which is now approved in Europe and soon in the U.S. and expect successful launches in current and future indications. And in addition, I would like to point out that our collaboration with Amgen has resulted in strong growth and access to these innovative medicines in the China market and meaningful potential global royalty streams if products like tarlatamab, which is their DLL3 and I can't pronounce the name of their STEAP1, sorry, are approved. So with that said, we're making substantial progress towards cash generation. On the chart on the left, you can see significant improvement in our gross margins. The main reason is twofold. First, product mix. Moving to BRUKINSA and TEVIMBRA, which are wholly owned and developed has dramatically helped. And secondly, our investment in internal manufacturing capabilities, which has significantly lowered our cost to produce our medicines. That's why we're investing in manufacturing and it is exciting to see this play out in gross margin, and we expect the trend to continue. The chart on the right shows our decreased adjusted operating losses from the 9 months ended in Q3 2023 compared to the previous year. You can see the improvement of more than $0.5 billion over the comparative periods. The trends are clear. We're rapidly shifting from a cash-consuming to cash generating. I know we don't provide guidance and haven't, but I think the results speak for themselves. So with this firm foundation in place, we're truly at an infection point for our business, and we'll look to build on the foundation for 2024. There's a lot happening in the company this year. This is a milepost for you to see the things that are occurring. For BRUKINSA, we're clearly doubling down on our best-in-class leadership and expanding key indications and geographies. We expect Q1 in follicular in the U.S. decision and for TEVIMBRA, many, many potential approvals. I think I would also like to point out that behind all this, which we haven't talked about, there's a very large randomized basket trial for Tisle combinations that are IO-IO. I know everyone is concerned will IOIO play out? We don't know. But we're trying. What we've been able to do though is run this in a very cost advantaged way in an intelligent basket trial for doublets and triplets, including combo for OX40, HPK1, LAG3 and look in those indications in a very affordable way. This is part of the reason we built those advantages. And from a first-in-human perspective, we have Phase 2 dose identification for SMAC mimetic, CCR8, DGK Gamma, CDK4, CDK2 and our initiating 4 new ADC programs, the EGFR degrader, PRMT5, pan-KRAS and bispecific antibodies, and we're excited about all of that. So let me just come back. What I hope I convinced you today is we're built very differently. We're built globally. We're built with a focus on how to have strategic cost and time advantages. Secondly, that we're already an innovative oncology leader in heme and we're rapidly becoming a leader in solid tumors with one of the largest oncology R&D teams and most compelling pipelines. And lastly, that next year, 1 year from now, we will have transformed into a very different company, a clear leader, clarified our path to profitability and our strategic advantages of cost and time have dispelled the misperceptions that are weighing on the company. And with that, I thank you so much for attending the session, and welcome any questions.

[Operator Instructions] We have one.

I would like to know is your BCL-2 inhibitor, one of your biggest assets for the next generation of growth? And how do you think about your competition with Ascentage's APG 2575, in combination with AstraZeneca's BDK? And are you doing this trying to extend your BDKs like patent protections or are you doing this just for this extra advantage in hematology?

We believe that our BCL-2 is clearly a best-in-class molecule, given its half-life, given its potency and given its selectivity. We have 600 patients worth of data, and I think we know it well at this point. And we are doing it because we believe it's going to have a huge impact and be able to go places that venetoclax hasn't gone. I think it also has very clear IP. So in terms of the other programs, I think from a preclinical and the data we've seen presentation perspective, we're not really focused on that as a competitive issue for us.

I'll jump in here. So we're almost a year into the U.S. launch for BRUKINSA in CLL. I'm curious what's the feedback you've been hearing from physicians as they adopt this agent? And what does that feedback make you think about the shape of the launch curve and the peak potential of the product?

Yes. I mean the feedback is pretty wonderful. And there was a lot of skepticism to be frank. We always had the clear we're sustainable inhibition. We have better PK. We're never providing a drug holiday during a 24/7 period. It was clear rationale, but I think that the top clinicians and most clinicians don't buy into that until they see the clinical data that really holds. I think they've seen the clinical data, which is helpful. But the biggest compliment that I get on the asset is when someone who's not tried it begins trying it and has been using the 3 primary BTK inhibitors, ibrutinib, acalabrutinib and zanubrutinib. And I think the feedback that we've gotten and that I've gotten personally is very favorable around both efficacy and safety. And I think there is a belief that there is faster and deeper response from some folks. So that's very positive. And the launch is everything we hoped it would be. And thank you, Jess, and your team. You're doing a great job.

So coming off of ASH, where we saw updates for multiple molecules in your pipeline for CLL. Can you talk about what you see that treatment landscape eventually looking like if we kind of fast forward 5 or 10 years? And where you see BeiGene's products fitting in sort of each stage of patients' disease?

Sure. Look, I think if we've learned one thing over time, it's that there's seldom one treatment that fits all. I think we think that the CLL landscape and the broader than CLL landscape will involve a range of treatments. From that perspective, we do believe that BRUKINSA is going to be a cornerstone of this. It's an incredible safe medicine with a very large data set at this point that has shown incredible efficacy and safety data. In addition to that, there are some people who are interested in fixed dose rather than continual medicine. For those patients, we do think there's an opportunity to combine with the BCL-2 and that, that can be compelling. Now those patients seem to have a good outcome for a while. Eventually, they will relapse and they will be retreated. But we see that as an important regimen for patients. From the greater perspective, it's an immediate cleanup. It's similar to Lilly's Perto, except in our view, it has the potential to be much more meaningful in that setting. So we're pushing that forward, and we think there's a clear place for it in that area. But I think broader, we think that BRUKINSA has been able to go place as the other BTKs haven't given its sustainable inhibition and the degrader may be able to, too. So we're looking at that in large B-cell lymphoma and Richter's and other indications as a potential combination partner. So overall, we think all of these are going to play an important role. We think CD20 bispecific will also, and there's still actually a substantial portion of patients that are seeing chemo at this point. So as it's evolving, we see this portfolio as an end-to-end potential to be working at all stages of the life cycle together and a part to treat patients with CLL and other indications.