This conference call is being recorded. I would like to hand the conference over to your speaker today, CFO Mr. Shiniu Wei. Please go ahead.
Thank you, Maggie. Greetings, everyone. Welcome to our 2023 Annual Results Conference Call for GenScript Group. I'm Shiniu, CFO at GenScript. Joining me today to present the prepared remarks is Ms. Sherry Shao, our group's rotating CEO. And also we've invited key leaders from the subsidiaries and business units to join us for Q&A later. And let's pause for one second for the forward-looking statement. In today's conference call, Sherry, our rotating CEO, will share our business highlights, and I will walk you through our financials and future outlook. We also have a Q&A session at the end of the call. Now I'll hand it over to Sherry.
Good morning, I'm Sherry Shao. It's a great honor to share our annual results with you today. First, let me give you a high-level overview. Despite the challenges in the market in 2023, our group's business has shown resilience and generated robust growth. This past year, we've seen remarkable revenue growth of 34.2%. Our 5-year CAGR stands at an impressive 30%. This success is a testament to the hard work and dedication of our more than 6,900 global employees. Their commitment is the driving force behind our achievements. Innovation lies at the heart of GenScript, and it's our core commitments. Reflecting this, over 10% of our workforce is dedicated to R&D. Their unwavering dedication has led to the accumulation of over 300 patents and 900 patent applications across the globe. This year, we also successfully raised capital for three of our subsidiaries.
As we reached the year's end, our group's cash reserves were approximately $2 billion. This strong financial position empowers us to further invest in R&D and expand our capacities. Our investment in innovation and the pursuit of excellence has created tremendous customer value over time. We have been serving clients in over 100 countries and regions, ranging from pharmaceutical and biotech companies to research institutions, as well as agricultural and consumer food enterprises. We are also making a significant difference in the lives of multiple myeloma patients with our best-in-class cell therapy product, CARVYKTI. Together, we are not just chasing growth. We are building a healthier and a more sustainable future. Now let's look at our segment highlights, starting with the life science group. We have always emphasized understanding industrial trends and innovation in our business.
In response to the increasing demand for CRISPR-related services and products, we have launched a comprehensive suite for invisible gene editing. Our offerings include gene editing tools, related enzyme ligation templates, library services, and cell line development. This platform enables our clients to accelerate research in this field. In CGT-related instruments and consumables, we are also advancing our cell isolation platform, CytoSinct, and we have also launched magnetic beads for NK, SA, CD4, CD8 cell separation, beads for T cell activation, and columns for cell separation. Turnaround time is crucial to our customers. We not only accelerate customer projects by innovative solutions but also by launching new platforms to shorten our turnaround time. We launched our GenSmart 2.0 online ordering platform to improve customer experience and simplify the ordering process.
We also combined TurboCHO 2.0 platform with our high-throughput DNA synthesis platform, stating an industry-leading turnaround time of five business days from gene to protein services. At GenScript, we believe science is the universal language that knows no borders. It's a collaborative pursuit that unites humanity in the quest for knowledge. Therefore, we launched our Life Science Research Grant Program globally. We believe this program will foster collaboration and promote excellence between the academic community and the industry, showing our dedication to shaping a better world through biotechnology. We are honored to have two new members join our scientific advisory board last week: Dr. Carl June, an immunotherapy pioneer, director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania; and Dr. David Liu, a leader in genome editing, professor at Harvard University, Broad Institute, and HHMI.
We believe their insights will empower GenScript to develop innovative services and products for the industry. Next page. We are committed to creating strong value propositions for our customers and helping them foster innovation and achieve breakthroughs by continuously enhancing our services. In 2023, we further strengthened our leading position in nucleic acid synthesis by introducing gene fragment synthesis services. Additionally, we introduced synthesis services for circular RNA and sa RNA. We also leveraged AI technology in our service offerings. Our AI-based codon optimization and enzyme design could help our customers accelerate research in their field. We continue to receive recommendations from our global customers. Globally, our life science active customer base is now over 57,000. New customers grew faster compared to last year. We also support the translational research of academic customers and industrial customers in order to transform scientific ideas into clinical assets.
As a result, we have a healthy mix with regard to customer composition. Roughly 80% of our business is from industrial customers representing biotech and pharmaceutical companies. In terms of regional performance, the Asia-Pacific region declined by 7% due to the funding environment. Our revenue growth remained strong in other regions. Next page. We provide top-tier capacity to our global clients. Last year, we achieved a significant reduction in turnaround time for our life science services, with gene-to-protein processes now taking only five business days in China and gene-to-protein processes eight business days in Singapore. Efficiency enhancements have also been implemented in our U.S. and Singapore facilities. To meet the growing demand for GMP-grade manufacturing in life science business, we are strategically increasing our capacity worldwide. Next page. Turning to ProBio, our biologics CDMO, we have further enhanced our capabilities in protein and antibody drugs and CGT platforms.
Starting with Discovery, our newly launched Hybridoma platform allows rapid identification of functional antibody binders in as fast as three months, shortening the turnaround time by over 30%. We also launched high-throughput semi-quantitative function assays, which enables functional screening using Hybridoma supernatants at the early phase of this discovery. In terms of development and manufacturing platform, we enhanced the titer of protein to 14.5 grams per liter and bispecific antibodies to 10 grams per liter. Additionally, our new Lean CMC solution for novel modalities has reduced the seed-to-tox batch delivery time to 3.5-4 months, facilitating quicker development in our customers' projects. We also continue to enhance our integrated capabilities for plasmid production. Our plasmid and mRNA one-stop solution offers six-month gene-to-GMP production. We constructed proprietary PowerS-ITR strain, which significantly improved the ITR plasmid quality, resulting in high plasmid sequence integrity and high production yield.
Finally, let's look at biovector. We significantly improved the AAV titer of AAV vectors with a 2-10-fold increase and optimized pRC plasmids, which enhanced the yield of AAVs. Our LVV platform processes improved with high recovery up to 50%, including both adherent system and suspension system. Next page. For the biotech and CDMO industry, 2023 was a challenging year, but we are committed to supporting our clients and accelerating their projects. In terms of our track record, we delivered 17 CMC projects, including an antibody drug, and 32 CMC projects in CGT. We also helped our clients earn 13 new R&D approvals in protein and antibody drugs and 18 new R&D approvals in CGT. Notably, we recently received our first 2,000-liter CMO order, which marked a significant milestone for our CDMO business.
The experience we gained from this project will enhance our commercial manufacturing capabilities and strengthen our commercial quality systems, paving the way for us to become a global CDMO. Next page. Although the industry is facing headwinds temporarily, we believe the long-term potential of biologic CDMO business, as more advanced therapeutics are under development and the need for manufacturing capability to support such industry trends, will be on the rise. We are committed to expanding our manufacturing footprint to better serve our customers globally. In 2024, we expect to launch our phase one of 16,000-liter commercial manufacturing capabilities. We are on track to launch our U.S. GMP plasmid facilities in Q3 2024, aiming to bring our competitive plasmid services to the U.S. market.
In order to support our global expansion, we have invested resources in our quality management systems to ensure compliance with GMP regulations of the U.S. FDA, EMA, and NMPA. These systems are crucial for our future CDMO business, and will also help us earn customer recognition globally. Next page. Moving to our industrial synthetic biology product segment, Bestzyme. Bestzyme delivered remarkable growth compared to peers in a single-digit growth enzyme market. Bestzyme achieved 22.6% enzyme portfolio constant currency growth. Our key account sales revenue contribution further improved by 4%. Our newly launched innovative detergent enzyme showed steady growth in the last few quarters and successfully earned industry-leading household product manufacturers as customers. We also expanded our product portfolio by launching products with new features and upgraded microorganism strength to increase production efficiency.
Thanks to our Series A financing for Bestzyme, we are able to further invest in our capacity in order to address manufacturing bottlenecks. Once finished the expansion project, we increased our manufacturing capacity by 30%-40%. In terms of workforce, we recruited experienced industrial salespeople who successfully boosted our revenue growth and helped us with key account penetration. In order to better address R&D needs for enzymes and synthetic biology, we expanded our R&D team by about 20%. To support our new market penetration plan, we are also actively expanding our local distributors in Southeast Asia and Americas. Next page. As for our synthetic biology pipeline updates, our first two synthetic biology candidates, Natural Sweeteners and Lactoferrin , are making promising results throughout the year. For Natural Sweeteners, we completed industrial-scale trial production.
Now we are targeting to finish product safety verification, preparing for the grant submission, and expecting to launch in 2024. For Lactoferrin, our product candidate finished pilot trial production in 2023. We are working with universities and clients on functional study. In 2024, we are aiming to seek grant certification and initiate industrial-grade trial production. We plan to commercially launch this candidate product in 2025. We believe these synthetic biology product candidates have tremendous opportunities in the future. Next page. Turning to our cell therapy segment, Legend Biotech. In the first seven quarters of its launch, our lead product, CARVYKTI, outperformed historical CAR-T launches, setting a new standard for CAR-T launches. CAR-T cells have cumulatively treated over 2,500 patients. In 2023, Legend continued its efforts to support market penetration of CARVYKTI. We presented positive PRO data from phase 3 CARTITUDE study at 2023 ASH annual meeting.
We are also strengthening our manufacturing capabilities. We have started committing to production at the new site in Ghent, and our cell processing capacity has doubled since the beginning of 2023. Other than our lead product, we are also unlocking value across broad pipelines. Recently, we received 100. Hi. Please remain on the line the conference will resume shortly. Next page. In terms of pipeline advancement, we are conducting label expansion studies for our BCMA-directed autologous therapy program in phase two and phase three. In other pipelines, we are conducting phase one clinical trials in the U.S. and China. We have two sites active waiting for LB1901, targeting Claudin 18.2 in gastric cancer. We expect to open more sites later this year.
In terms of autologous cell therapy, we are conducting IIT trial for LB2103, targeting BCMA for the treatment of multiple myeloma in China, evaluating safety, PK, and preliminary anti-tumor activity. For the CAR-T pipeline, targeting DLL3, where we have an exclusive global license agreement with Novartis, we are conducting phase 1 clinical trial, LB2102, for the treatment of extensive-stage small-cell lung cancer and large-cell neuroendocrine carcinoma. The U.S. FDA granted the product candidate orphan drug designation. Next page. To meet marketing needs for CARVYKTI, we are collaborating closely with our partner, Janssen, to boost our manufacturing capabilities, expecting to launch new facilities in the U.S. and Europe. Our CMO partner, Novartis, is also on track to produce clinical materials in first half 2024. In response to the industry-wide shortage of lentivirus, our partner, Janssen, will further expand its in-house lentivirus capacity for CARVYKTI.
In late December, we received approval to expand the antivirus capacity from 20-liter to 50-liter tanks, more than doubling capacity. We are confident in manufacturing ramp-ups and will bring CARVYKTI to more patients. That concludes the update on business highlights. Next, I would like to invite Shiniu to share the company financials.
Thank you, Sherry. Hello, everyone. For those of you following us online, we are on slide 18. I'm going to walk you through our financial performance. In 2023, the group's business continued to grow at a fast pace. The group's revenue increased by 34.2% year-over-year to about $839.5 million. Adjusted net loss of the group narrowed to about $298.2 million. Among others, the Life Science Group achieved external revenue of $404.5 million, maintaining a healthy growth rate of 15.6%. Due to the headwind in biotech funding environments, external revenue of ProBio declined to $106.7 million.
External revenue of Bestzyme grew about 12.2% to $42.9 million. ProBio demonstrated strong commercial potential in 2023, resulting in 144.2% explosive revenue growth for Legend. In terms of our operating profitability, the Life Science Group achieved adjusted operating profit of about $78.3 million, increasing 19.4% year-over-year. ProBio had an adjusted operating loss of about $29.7 million. Bestzyme's adjusted operating profit was about $2 million. Legend's adjusted operating loss narrowed to $394.5 million. Now, let's look at Life Science performance on slide 19. The Life Science Group continued to maintain stable growth with improved profitability. External revenue was $404.5 million, representing 15.6% growth year-over-year. The revenue growth at constant currency was about 16.4%. Among different service lines, we continue to leverage our core strength. Molecular biology, protein, and peptide grew at a faster pace, contributing to a higher percentage of overall revenue.
The adjusted gross profit increased by about 11.6% year-over-year to about $224.5 million. The adjusted gross profit margin for Life Science was about 54.4% for the full year. Thanks to our efforts on automation, lean project management, and labor efficiency improvements, our gross profit margin has stabilized. More importantly, the adjusted operating profit of Life Science business increased by about 19.4% year-over-year to $78.3 million, which outpaced our revenue growth. The adjusted operating profit margin increased to about 21% in second half 2023, continuing a healthy trend of improvement in the last two years. Turning to slide 20, external revenue of the ProBio business decreased by about 12.0% to around $106.7 million. The drop was mainly due to the slowdown in biotech funding environment and slower biotech spending. The adjusted gross profit of ProBio decreased to $19.8 million.
Dropping gross profit was due to lower capacity utilization and price competition. Also, gross profit was negatively impacted by one-time raw material inventory write-down of about $4 million. In terms of revenue structure, protein and antibody business accounted for 60% of the revenue, while cell and gene therapy projects make up the remaining 40%. Regional revenue maintains a similar structure to what we saw last year, with China market contributing to about half of ProBio's revenue and ex-China market contributing the other half. In 2023, we reviewed our R&D priorities and focused on high-value-added projects, which resulted in a slight drop in R&D expenses for ProBio. However, administrative expenses increased about 19% compared to the same period last year, mainly due to the rise in management costs associated with the construction of the U.S. plasmid facility. ProBio's adjusted EBITDA was $1.3 million.
With a year-end cash position close to $260 million, ProBio has ample resources to execute our business plan. Turning to slide 21, Bestzyme's external revenue was about $42.9 million, representing 12% growth year-over-year. Core enzyme portfolio constant currency revenue growth was about 22.6%. Thanks to our experienced sales team and key account strategy, constant currency revenue from seed enzyme business grew about 24%, while constant currency revenue from industrial enzyme business grew about 21%. The gross profit margin decreased about 2 percentage points to 38%, with adjusted gross profit of $16.6 million. The core enzyme portfolio, excluding patent licensing and gallic acid business, has a stable 40% gross margin year-over-year. We have confidence in profitability of our enzyme business. With revenue growth at a fast pace, the profitability of enzyme portfolio has the potential to further improve.
Selling and distribution expenses increased due to our increased marketing activities. On slide 22, in the year of 2023, Legend generated $285 million in external revenue, representing an increase of 144.2%. Of Legend's revenue, product revenue was about $250 million, and $35 million comes from milestone revenue. Expense-wise, the largest part of our expense at Legend was incurred by R&D, including ramp-up in cilta- cel clinical development activities and continued investment in other pipelines. Increasing administrative expenses was primarily due to the expansion of the administrative functions to facilitate continuous business growth and continued investment in building global information technology infrastructure. Selling and distribution spend was relatively flat. Notably, Legend has a solid balance sheet. Legend's cash position of $1.3 billion is expected to fund operating activities and capital expenditure plans throughout the end of 2025. Now, in summary, we have the following key takeaways of today's call.
Despite funding challenges, Life Science Group continued its 21 years of revenue growth. On top of that, we're improving our profitability. Our gross profit margin stabilized and operating profit margin increased. For ProBio, 2023 was a challenging year, but we are accelerating our business by improving operational efficiency, executing a global strategy, and focusing on capturing opportunities from industry-leading clients. After years of unwavering dedication and investment, Bestzyme achieved outstanding growth compared to industry peers. We expect profitability to gradually improve alongside revenue growth. Meanwhile, we're exploring synthetic biology products that have the potential to create significant value in the future. CARVYKTI has proven itself as the fastest-launched CAR-T product. Along with our partner, Janssen, we are confident that we will advance global launches and label expansion for this product. We anticipate peak sales for CARVYKTI to reach at least $5 billion.
I'm also excited to share with you that after reviewing our business performance in Q4 2023 and the first two months of 2024, we are cautiously optimistic about the industry environment. This leads to our refreshed 2024 guidance on page 25. We expect Life Science Group revenue to continue to grow at a decent pace between 15%-20% and gross profit margin to be around 55% ±1%. We anticipate operating profit to grow at a faster pace than revenue for Life Science Group. We also expect ProBio's revenue to be flat compared to 2023. For ProBio, 2024 will be a year of investment. We will invest in commercial efforts, R&D, and capacity in order to reaccelerate order growth. For Bestzyme, its growth trajectory will continue.
We expect 20%-30% constant currency revenue growth from our core enzyme business and gross profit margin to be around 39% ±1%. We anticipate operating profit margin to be close to 4%-5% for this business. For Legend, we expect to receive label expansion approval for Carvykti from U.S. FDA and EMA. We also will complete enrollment for CAR-T5 program in first half 2024. In terms of capacity expansion, we are targeting to support production capacity of 10,000 annual doses of Carvykti by the end of 2025. This concludes today's prepared remarks. Operator, let's open up for Q&A.
Thank you very much. We will now conduct the question-and-answer session. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please note, in today's conference, you are allowed to ask one question and one follow-up question. Thank you. Please stand by as we compile the Q&A roster. Just a minute, please. Our first question comes from Lin Hua Zhao of Goldman Sachs. Please go ahead.
Hi. Thanks for taking my question. I'm Lin Hua Zhao from Goldman Sachs. I'm particularly interested in our observations in ProBio in the second half of 2023. How do you see the observed growth of the two subsectors, the Antibody Drug and CGT, in the second half of 2023? And you mentioned a lot about the slower biotech funding environment, the increased competition, and the low utilization of our facilities. And how do you see the potential recovery in ProBio for the next two years? And specifically, we are having a year of investment in 2023 for ProBio. How do we see the continued lower gross margin for this sector? Thanks.
Thank you, Lin Hua. We also have our new ProBio CEO, Dr. Li Chen, on the call. So I would like to invite her to give commentary to this question. And Li, please.
Sure. Thank you. Can you hear me? Hello? Can you hear me?
Hear you.
Yeah. Thank you. Thanks for joining the call today, and I appreciate your question. As you stated, the macroeconomic environment and the stock-to-investment in China and the U.S. moderately impacted our sales and revenue in 2023. While our regional contributions remain unchanged, it is important to note that our U.S. and Europe business expansion is still in its early phase. Hence, we believe in the significant potential for growth. We continue to build our differentiated viral vector and mRNA offering to serve the end-to-end CGT customers. Looking ahead, we remain optimistic about the long-term prospects of both the biologics and the CGT segments, and we are committed to capitalizing on the growth opportunities in the global market.
Thank you, Li. And Lin Hua, in terms of your question about gross profit margin performance and other details, since we are in an early stage of a turnaround effort for ProBio, and our top priority is to execute our strategy and reaccelerate order growth, so at this moment, we cannot give you the gross margin and cadence for 2024. But we will update you on our next call.
Thanks. A very quick follow-up on our U.S. and EU businesses. I know that we are building the U.S. plasmid facility, which is on track to be operational in 3Q this year. How do you see the potential impact of the recent BIOSECURE Act passed by the U.S.? And in general, can you elaborate more on the exposures and the challenges we may potentially see for our businesses by the act? Thanks.
Sure. I think for this question, I will invite Sherry to speak about it.
Thanks for asking the question. It's difficult to say the exact impact since the legislation process is ongoing. From what we understand preliminarily, we don't think there is a meaningful impact to us. GenScript Biotech is a leading provider of research and production services for life sciences and the pharmaceutical industry. We provide innovative solutions for the sustainable development of global life sciences and the environment. Our business has been and will always be based on the tremendous value we create for our customers and patients globally. To better serve our global customers, we have the long-term capacity expansion strategy and plans in different locations, and we will continuously execute our plans. We will continue to closely monitor the progress on this matter.
Thanks. Appreciate your answers.
Thank you. Our next question is from Wan Huan Wu from CICC.
Okay. Thank you so much for giving me this opportunity to have questions. I have two questions. The first one is for ProBio. After new CEO, Dr. Li Chen, took office, is there any change of ProBio, especially in terms of strategic change and customer expansion?
Sure. Shiniu, you want me to take this question?
Yeah. Li, please comment. I will also have Dr. Liu, Patrick Liu, who is Chairman of ProBio, to give his comment as well. Li.
Okay. I'll start first. Thank you for your question. I'm delighted to take this one. So in 2024, we will laser-focus on the following things: first, revitalize our core business, drive the top-line performance by building our strong commercial module in the US, building robust market operations, including brand awareness. We will also ensure the firm execution in operational excellence, building our capability and capacity to support the global customer's need of local supply, shorten lead time, and better manage the risk resilience. We will also focus on improving our operational efficiency, ensure our quality and speed of service, improve the labor efficiency, and P&L. We will upgrade to the global quality management system, and last but not least, innovation. We will continue to invest in innovation to improve our technical core competency, to better serve our customers, and to better differentiate ourselves in the market.
Okay. Yeah. So I just made an additional comment. And so basically, for ProBio, we have been in the business for many years, although the legal entity was formally founded roughly 5 years ago. And I think everybody is aware that we had a leadership change last year. And I think we believe that ProBio has a very mature and well-established management team over the years. Obviously, CEO is definitely keeping this. The one who can drive the things forward. And we are very glad to have Dr. Li Chen on board. She has been here for just over three months. And so Dr. Li Chen has many years of experience in the life science and high-tech business. And so she excelled in strategy formulation, business planning, and also was very good at building a team, building a high-performing team in her past experience.
During the three months, we have seen a very strong recovery in terms of team spirit and of the business. Also looking forward, we believe that under Dr. Chen's leadership, we will have a very promising year for 2024. Thank you.
Thank you, Li.
Okay. Thank you so much. Thank you so much. My second question is about Legend and about its capacity. How much production capacity of Carvykti will include?
Wan Huan, I think you went off for a second. Alfredo?
We have Alfredo on the stage at the moment. Do you want to go back and answer her question?
Wan Huan, I think we did not hear Wan Huan's question completely, but I do think it's about capacity expansion plan for 2024 for CARVYKTI production. So we have CEO of Legend Biotech, Dr. Ying Huang, online. So Ying, would you like to comment?
Yes. Thanks for the question. Capacity. So we do not provide specific guidance for 2024 capacity and 2025 capacity. But what I can tell you is that we and our partner, Janssen, have laid out a plan to get to 10,000 doses annually by end of 2025. Right now, I can tell you everything's on track. In New Jersey, we doubled our capacity last year as approved by the FDA. And we're continuing to expect a couple of ramp-ups approved by the FDA this year for year of 2024. We're also undergoing physical construction to double our manufacturing area in the New Jersey facility. That construction should be completed this year. And we should start to do the validation and the CGMP prep works by end of this year.
Hopefully, sometime next year in 2025, we will be able to utilize the full, roughly 210,000 sq ft manufacturing area in the New Jersey facility. In Belgium, as you can see, we already started clinical trial production from our first stage of Belgium facility, which is Obelisc. Right now, we're expecting the commercial production for Carvykti to start in the second half by end of this year from Obelisk. For the other much larger facility in Ghent, what we call Tech Lane facility, we are planning to finish all the physical construction by end of this year. That means early next year, we should start, again, clinical production from Tech Lane. About third quarter next year, we should start commercial production from Tech Lane.
All three internal nodes are right now on track to deliver the expansion as we planned in the beginning of last year. Like I mentioned, we're on track to achieve that global combined supply of 10,000 doses per year by end of 2025. Thank you.
Thank you.
Our next question comes from Wilfred Yuen of Daiwa. Please go ahead.
Okay. Thank you for taking my question. My question is on the life science segment. So our revenue growth guidance is 15%-20% growth. So what is the factor driving it to the sort of higher end of the guidance? And is it due to the region, as I saw the Asian demand drop in 2023? And for the margin, I saw slight improvement in the gross margin in the second half on both quarter-on-quarter and year-on-year basis. And we also saw a stronger improvement in operating margin at 21%. So what's the reason for the improvement, and how should we think of in 2024? What are the key driving factors for both margins? And lastly, can you give us more color in terms of the overseas facilities, I think, in the US and Singapore, and how much they can drive the overall margin in 2024? Thanks.
Okay. Wilfred, thank you for the question. For overall executing strategies this year for life science business, I would like to have Sherry to give you some high-level commentary. And I'll give you a little bit more specific color on the margin improvement.
Thanks for the question. For life science, especially the U.S. and Singapore capacity, we started 2-3 years ago. Currently, we are continuously improving the delivery capability and the operation efficiency. We just launched the three-day rocket gene synthesis service in the U.S. facility in December. We also upgraded our gene-to-protein antibody to 8 business days in the Singapore facility. So the capabilities could better serve our global customers. We are also improving the efficiency and the profitability. We will continue to improve it.
Thanks, Sherry. In terms of our margin performance, Wilfred, if you look at our life science business last couple of years, we did saw a gross profit margin decline initially. This was due to two factors. One was the non-repeating COVID business, which was very high margin, but that's behind us. But also, more importantly, in our core life science business, we have been servicing bigger-scale customer projects over time. And those kinds of projects do have slightly lower gross margin, but we are better at leveraging our other capabilities to improve operating margin. And also, as Sherry had mentioned, as we continue to ramp up our operations in the U.S. and Singapore, the margin there is also improving. Overall, we are very confident that we will be gradually improving our operating margin over time. Thank you.
Thank you for the question. Our next question comes from Ethan Ding of Bocom International.
Congratulations on the strong results. I just have one quick question from me. On Legend Biotech, I think our competitor, BMS, is having an adcom meeting later this week. Our CARTITUDE-4 data might be discussed at that meeting as well. Could you discuss what we can expect from the meeting and how the meeting and the results are going to impact our upcoming PDUFA? Also maybe just maybe just maybe what's your quick take on the rising competition globally in the BCMA space? Thank you.
Ying, would you like to comment?
Sure. So Ethan, thanks for your questions for Legend. First, on ODAC, as you can tell from the Federal Register, which was published about a month ago, we will also go over an ODAC meeting on the morning of March 15th, this coming Friday. Then our competition's applications for third line will be discussed at ODAC, the third the same day on the afternoon of the 15th. So based on communication from the FDA, we know that the focus for our ODAC discussion will be overall survival benefit. So in that context, we have submitted already by now three batches of overall survival data to the FDA and also to the EMA for the application in Europe. The first one was as of data cut of November 1st of 2022. That was part of the first pre-specified interim analysis of CAR-T24.
And then as part of what we call day 120 safety update for the sBLA, we submitted to the agency in October another data cut for overall survival. And that was with the data cut in April. And then lastly, in January, we submitted another data cut of survival as of December 13th of last year. So at this point, the regulators, including FDA and the EMA, have access to all latest survival updates. And we have very high confidence in the survival benefit CARVYKTI provides in this patient population within CAR-T24. So we feel confident about the outcome of ODAC on the 15th. And now your second question about competition.
Right now, based on what we have seen so far in the clinic, we continue to believe that Carvykti is the best-in-class BCMA-directed therapy in the setting of multiple myeloma in late line and now in second line as well. So we feel that we continue to have the best-in-class efficacy in the whole field. And we feel good about it. Of course, it's very important for us to get into the second line market as quickly as possible. As you know, in Europe, we did secure official CHMP positive opinion. So we're expecting by end of next month, we should get official European Commission approval in second line. And then we also hope that on the PDUFA date of April 5th, we will get the FDA approval in second line. Therefore, we'll be the only BCMA-directed agent in the treatment of second line multiple myeloma.
That's our strategy. Thank you.
Thanks, Ying. Ethan?
Thank you. Thank you for all the questions. We will now conclude the Q&A question session. I would like to hand back the conference to Mr. Wei. Thank you.
All right. Thank you, operator. Thanks to all of our shareholders, investors, and analysts for your continued support and care. We will see you on our next call. In the meanwhile, if you have any questions, please feel free to contact our IR team. Bye-bye.
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.