Good afternoon, welcome to our 2022 full year results presentation. I'm Gordon Sanghera, Chief Exec of Oxford Nanopore, I have with me today Tim Cowper, our CFO. I will provide a short summary of our financial highlights for 2022 and key business highlights for the year. Tim will walk you through our financials in more detail. The company's vision is to enable the analysis of anything by anyone, anywhere. This slide shows a overview of the company, a summary of the company. I will leave you to read that at your leisure. I would like to move directly to the results summary. We saw continued momentum in our business in 2022. Our total revenues for 2022 were GBP 198.6 million. This included a GBP 51.8 million one-off legacy COVID testing LamPORE revenue DHSC contract settlement.
The core life science research tools revenue was GBP 146.8 million. Overall growth, including EGP and COVID sequencing was 16%. Excluding EGP and COVID sequencing and currency, the underlying growth was 30%. A key metric for our business is the number of publications. In 2022, our customers published 3,000 papers highlighting the breadth, depth, and diversity of Nanopore sequencing applications. As I've just said, our core life science research tools revenue was GBP 148.6 million. 76% of this revenue comes from consumable sales. We've increased our customer base from approximately 6,300 to 8,200. Our gross margin increased approximately 250 basis points to 56.3%, and we have a cash position of GBP 558 million of cash and cash equivalents. We are seeing strong momentum across the business.
We are delivering on revenue and margin. We continue to push the boundaries of uncovering the dark genome, as well as continuing to innovate on our platform. We continue to simplify end-to-end workflows, as well as launch new applications. We've doubled our commercial headcount since the IPO to meet the growth and commercial targets we set out at IPO. I shall give you a few examples of that later. Innovation is and remains at the heart of our strategy. On our platform, we launched P2 Solo, and we have a strong order book. We also launched our Short Fragment Mode, making nanopore sequencing the only platform that can address any read length from 20 base pairs right through to millions of bases. We are also providing NVIDIA's A100 GPUs, increasing our basecalling speed and enabling full methylation analysis.
We continued to upgrade the electronics on our P24 and P48 in-field fleet, providing the latest hardware to run our latest chemistries. In 2022, we transitioned our Q20+ chemistry kit from developer to broad early access. Our simplex single-molecule accuracy is 99%. With consensus, we deliver accurate small variant calling comparable to short-read sequencing. In addition, we provide structural variation and methylation. Our simplex chemistry routinely delivers in-field 100 GB of sequence data per PromethION flow cell. Our duplex single-molecule accuracy is 99.9%, improving rare variant and de novo assembly of genomes. We are seeing in-field replication of our Q20+ accuracy in the hands of customers. Currently, full Oxford Nanopore sequenced genomes are available from $345 on our PromethION platform, with a technology roadmap to sub $200 per genome.
Remember, this includes short reads, long reads, full methylation, plus copy number variation, structural variation, and all in one cost-effective run. We continue to make good inroads into the GBP 6.2 billion sequencing market for life science research tools. This market is growing at approximately 15% per year. At this point, I am going to hand over to Tim, who will give us a deeper dive on the financials, and I will come back at the end and talk about some use cases, particularly on the applied market side.
Thank you, Gordon. Good afternoon, everyone. During 2022, we have continued to deliver a strong financial performance while investing in driving future profitability. Firstly, we delivered strong revenue and margin growth in our core LSRT business. LSRT revenue was up by 30% on an underlying basis and up by 16% on a reported basis. LSRT gross margin increased by approximately 250 basis points despite global supply chain challenges. Total revenue was GBP 198.6 million, including GBP 51.8 million from our legacy diagnostic sales related to COVID testing. We continued to invest for the future with a focus on innovation and commercial infrastructure. Adjusted EBITDA, an alternative performance measure, was a loss of GBP 78.6 million compared to a loss of GBP 57.7 million in 2021.
This reflects a 48% increase in commercial headcount in the period and a 39% increase in adjusted R&D spend. In addition, post-period end, we achieved the goal we set out at IPO of doubling our commercial team. Despite significant investment in R&D and commercial infrastructure, we finished the year with cash equivalents, and liquid investments of GBP 558 million, representing a net cash burn of GBP 60.2 million during the year. Let's look more closely at LSRT revenue. There are a number of figures on this slide, but the key message I'd like to leave you with is that the underlying revenue, excluding the EGP, COVID sequencing, and foreign exchange, was 30%. This growth is driven by new customer acquisition.
Including the EGP and COVID sequencing, LSRT revenue growth was 16% on a reported basis and 10% on a constant currency basis. This includes a significant headwind from the EGP, down GBP 17.4 million year-on-year, which was partially offset by a year-on-year increase in COVID sequencing of approximately GBP 8.6 million. EGP revenues declined in part due to accelerated orders of consumables in the fourth quarter of 2021, which reduced their demand for flow cells in the first quarter of 2022. Let's look at LSRT revenue by category. Starter Pack revenue increased by 23%. This growth reflects increased customer acquisition in 2022. Consumable sales grew by 12% in the year to GBP 95.7 million. This was despite a GBP 15.5 million decline in consumable spend by the EGP.
This decline was offset by a continued increase in consumable utilization from our broader customer base across all geographies and all customer types. Excluding the EGP, consumable revenue increased by 43% in 2022. As a reminder, consumables consist of the flow cells and preparation kits that customers purchase separately after they have completed their Starter Packs. New customers acquired in 2022 will drive consumable growth in 2023. Let's look at the revenues by customer type. We focus on our customers and segregate them by revenue size into three categories: S1, S2, and S3. We delivered strong revenue growth across all customer groups in 2022, excluding the EGP. On the left are the S1 customers. Total revenues in this group grew by 29% in 2022.
Growth accelerated in the second half with H2 revenue growth of 44% compared to 16% in the first half. The relationship we announced with our channel partner, Avantor, 18 months ago is working well, and this is reflected in the strong S1 growth in the second half. As a reminder, Avantor are helping expand our commercial reach for entry-level products such as the MinION in Europe and North America. They are driving both new business and ongoing consumable business. The direct contact has also seen the reactivation of entry-level devices already in customers' hands. Revenue from the S2 customers grew by 36% in 2022, driven by an increase in customer acquisition.
Whilst COVID sequencing accounted for approximately 20% of S2 revenue in 2022, S2 is a very diversified group, including human genetics, clinical research, cancer research, and work on infectious diseases. Other areas include plant and animal research, environmental studies, and microbiology. Revenue from the S3 group, excluding the EGP, grew by 33% in 2022, reflecting strong growth in the broader underlying customer base. Population genomics, including the EGP, represent about a third of total S3 revenue, dominated by seven customers. COVID sequencing by S3 customers contributed approximately 19% to S3 revenue in 2022. S3 revenue growth significantly slowed in the second half of 2022. H2 revenue declined by 5% in the second half compared to 94% growth in the first half.
This is primarily due to the high level of COVID sequencing by S3 customers in the second half of 2021 compared to the low level of COVID sequencing by S3 customers in the second half of 2022. Finally, we are increasingly investing in improving the level of service to more difficult to reach countries. We rely on an expanding network of regionalized distributors to help us. Revenue for these indirect customers increased by GBP 8.4 million or 86% in the year, which was largely due to growth in China. COVID sequencing accounted for approximately 25% of indirect revenue. Turning to the next slide, you can see that this revenue growth was driven by a significant increase in active customer accounts.
We delivered a net increase of more than 1,900 active accounts in 2022, taking total active customers to more than 8,200. S1 customer numbers increased significantly to 7,210. S1 average revenue was $5,200 per customer in this group, down from $5,800 in 2021, reflecting the significant increase in new accounts. We also added over 200 new active customers in this S2 group, while maintaining average revenues of $66,000. Average revenue per account declined slightly due to the increase in new customers as well as movements between groups. We also delivered a net increase of 17 customers in the S3 group.
You can see, average revenue per account, excluding the EGP, declined by 8%, which is predominantly due to a number of customers moving up from S2 to S3. Importantly, if we look at customers that were in the S3 group in both 2021 and 2022, average revenue per account increased by 18% in the year to $898,000. I have said, 2022 has been a year of customer acquisition, which will drive growth in 2023. Moving to regional results for our LSRT revenue. Revenue across the Americas was GBP 48.3 million, up 45% or 32% on a constant currency basis. This reflects increased investment in commercial resources and growing demand for our unique technology platform.
Revenue growth in this region is principally driven by research in human disease and genomic surveillance in the U.S. and Canada, but also reflects the expansion in South America through an emerging network of distributors. Revenue in Europe was GBP 43.3 million, up 30% or 29% on a constant currency basis. Revenue growth reflects the increased commercial headcount across the region. Rest of world revenue was GBP 39.8 million, up 40% or 33% on a constant currency basis. This includes very strong revenue from China, up by GBP 8 million year-on-year. Increased demand in China was driven by strong performance of MinION and GridION for infectious disease. Now let's move to gross margin.
We spent a lot of time investing in our supply chain and making operational improvements in 2022, including automation, improvements in manufacturing techniques, and the recycling of electronic components. As a result, we delivered a 250 basis points increase in LSRT gross margin in 2022, despite significant global supply chain challenges and inflationary pressures. We also benefited from our decision to maintain high inventory levels of core components, our long-term relationships with suppliers, and our core internal capabilities. For example, we were able to navigate supply shortages by purchasing and adapting alternative generic components to work in our products. During the second half of 2022, we continued to make further progress on driving margin expansion. LSRT gross margin in the second half was 57.8%, up approximately 300 basis points from the first half.
We have increased investment in innovation and expanded our commercial infrastructure to drive future growth. In terms of headcount, we ended the year with more than 1,000 employees, up from 803 at the end of 2021. Reported R&D expenses of GBP 64.8 million include the reduction in the provision for social security costs on pre-IPO share awards. Excluding this item and adding the capitalization of development costs, the total spend on R&D increased by 39% in the year to GBP 93.9 million. This was principally due to a 31% increase in R&D headcount. Reported SG&A costs were GBP 157.4 million, down from GBP 161.8 million in 2021. After adjusting for share-based payments, adjusted SG&A expenses increased by 18%.
This was principally due to a 48% increase in the commercial team and a 30% increase in corporate staff in the period. You can find a reconciliation of adjusted R&D and SG&A expenses in the appendix. Adjusted EBITDA, an alternative performance measure, was a loss of GBP 78.6 million compared to GBP 57.7 million in 2021. This includes adjustments for the settlement of the DHSC contract, share-based payments, and the sale and leaseback, as you can see on this slide. Moving now to guidance. We expect annual LSRT revenue growth of greater than 30% on an underlying basis in both 2023 and in the medium term. As a reminder, underlying revenue growth excludes the EGP, COVID sequencing, and foreign exchange.
Including the EGP and COVID sequencing, we expect full year 2023 revenue growth to be in the range of 16%-30% on a constant currency basis. This includes a significant headwind from COVID sequencing. As I have previously discussed, there was some volatility in the EGP and COVID sequencing revenues over the last 2 years. This is reflected in our overall growth in 2022 and guidance for 2023. This is now largely behind us and isn't expected to impact forecasts going forward. The 3-year contract signed with the EGP in 2021 is now expected to continue in the range of GBP 15 million-GBP 20 million per year until the contract completes in November 2024. We believe that COVID sequencing has now largely stopped.
As such, we expect COVID sequencing revenues of approximately GBP 6 million in 2023, which reflects a year-on-year headwind of approximately GBP 20 million. We do not expect COVID sequencing revenues in 2024. Our margin targets are unchanged. We are targeting greater than 60% gross margins for the financial year 2023, and greater than 65% in the medium term. We also continue to target Adjusted EBITDA break-even by the end of 2026. Before I turn back to Gordon, I would like to quickly summarize the four key takeaways. First, the core business is doing well. 2022 was a year of strong customer acquisition. Those new customers will drive consumable growth in 2023. Second, we delivered very strong gross margin progress despite significant global supply chain challenges in 2022.
The operation improvements we have made will continue to drive margin expansion in 2023 and beyond. Third, we have a strong balance sheet with cash equivalents, and liquid investments of GBP 558 million. Finally, we are very excited by the progress we are making in new market applications. This will be a key driver of long-term growth, which Gordon will discuss in more detail. Over to you, Gordon.
Thanks, Tim. I want to finish off by discussing how our technology is being used in discovery and translational research, and early progress towards applied market, clinical, and industrial applications. In discovery and translational research, we are working with the NIH, who are sequencing brain samples from dementia patients, with a particular focus on elucidating structural variants and the association with neurodegenerative conditions such as Alzheimer's. Cancer 2.0, our collaboration with Genomics England, is moving into year two of this study, with two genomic laboratory hub pathfinder labs starting pilot programs to deploy cancer genomic insights into the NHS. Building on the work previously reported on same-day sample to answer on whole genome sequencing at Stanford, they are now expanding the program to resolve hard-to-diagnose disease faster than ever before.
Here in the U.K., the Royal Devon & Exeter NHS Foundation Trust are looking to deploy rapid whole genome sequencing to evaluate benefits in care pathways for human genetic disorders. On the infectious disease front, we're building on our placement of nanopore sequencing in public health labs during the pandemic. We're focusing on rapid genomic surveillance in a post-COVID world, from avian flu to monkeypox. The ONT platform was the first to sequence avian flu in an 11-year-old Cambodian girl. At Guys & St Thomas', they've been running a proof of concept trial providing daily respiratory metagenomic services to characterize pneumonia and respiratory infection in the ICU. 200 results have been returned same day versus 3 days-4 days in a traditional path lab.
Guy's & St Thomas' were also at the forefront of sequencing isolate samples from the recent U.K. strep outbreak, providing novel insights into invasive cases and pediatric deaths. On the TB front, the drug-resistant workflow, we are looking to extend and run further proof of concept clinical studies in public health laboratories where, in countries where there is high prevalence of TB. In my final section, I would like to focus on our collaborations to accelerate Nanopore sequencing into applied markets in clinical and industrial applications. As you may have seen last week, we announced our collaboration with Cyclomics. Cyclomics is developing a kit, a workflow to access liquid biopsies. Just to remind you, liquid biopsy is cell-free or circulating tumor fragments of cancer cells. These fragments provide early detection of cancer compared to traditional technologies.
Cyclomics have developed a workflow that enables highly sensitive and accurate methods for detecting circulating tumor or cell-free DNA on a MinION. They have demonstrated on head and neck cancer samples near 100% accurate sequencing of the gene TP53, which has very low abundance mutations for head and neck cancer. Our collaboration will enable Oxford Nanopore customers to access the Cyclomics workflow as an early access developer. Longer term, we expect this approach to be adopted for early detection of cancer in clinical settings. Our 4bases collaboration on breast cancer, we've signed a strategic collaboration with 4bases, a Swiss company that develops and markets CE IVD genetic diagnostic solutions and assays. 4bases has tested the use of Oxford Nanopore platform with its kits, will supply them together for breast cancer screening in Switzerland and Italy.
The 4bases kit targets the BRCA1 and BRCA2 genes through PCR generating short amplicons, which are compatible with Oxford Nanopore's built-in Short Fragment Mode sequencing, enabling the identification of variants present in these genes to provide a report listing the mutations to the end users. This is exciting as it has the potential to enable results near the point of care and with faster turnaround times. Our Asuragen collaboration focuses on carrier screening. Asuragen and ONT will develop assays designed to deliver more accurate and reliable options for reproductive health and carrier screening. Asuragen will leverage its gold standard PCR technology with Oxford Nanopore's DNA sequencing capabilities to develop the first sequencing system to identify the most challenging yet highly prevalent carrier genes in a single unified work stream that today requires multiple methods.
Although traditional sequencing methods allow identification of large numbers of genetic sequence variants, they cannot effectively resolve the many problematic genes such as those with tandem repeats, copy number variation, structural variation, and pseudogenes. These are genes that are recommended in professional practice and guidelines for carrier screening. Six of the 10 genes with the most common pathogenic variants in carriers are difficult to genotype using traditional short-read sequencing methods and often require complex and complicated combination of solutions. Oxford Nanopore and Asuragen will develop a comprehensive carrier screening assay. I'm gonna switch now to talk about an emerging customer segment, which is pharma, biotech, biologics, QA, and QC manufacturing. All vaccines, biologics, and therapeutics require mandatory testing to ensure they are safe and effective. ONT has the potential to offer significant advantages within the genetic characterization, safety, and contamination investigation space.
This is a highly regulated market, and we are very excited about our PathoQuest collaboration. PathoQuest is a spin-out from the Institut Pasteur in Paris and is a leader in using NGS-based testing for quality control of biologics, enabling rapid, robust analysis at a GMP level. PathoQuest and ONT have signed an MOU for a collaboration with the objective of optimizing and commercializing a testing service for non-GMP and GMP-validated Integration Site Analysis tests for biomanufacturing quality control. The development of regulated platforms will be a key enabler in penetrating the biopharma QA/QC testing market. Finally, in summary, we continue to execute on innovation, our new products and upgrades to existing platforms driving adoption. Our platform performance continues to improve through accuracy, output, and reliability with full rollout of our fleet upgrades and Q20+ chemistry.
We are simplifying our workflows and improving analysis software pipelines, which are key drivers of growth. Operationally, we are making progress in automation and manufacturing improvements to drive reliability and margins. We are enhancing our customer experience through key technology partnerships such as the A100 upgrades with NVIDIA. On the commercial execution front, we're delivering on our commitments of growth in the life science research tools market, and as I've just discussed in the second part of my talk, progress towards applied market, clinical, and industrial applications. With that, I will hand over and look forward to questions.
Thank you. If you would like to ask a question over the phone, please press star one on your telephone keypad. To withdraw your question from the queue, it's star two. Again, please press star one to ask a question over the phone. We'll take the first question from Charles Weston from RBC. Please go ahead.
Hello. Thanks for taking my question. My first is around the commercial team. You've retooled it in terms of capabilities and scale. How should we expect this to translate to growth in the various different customer groups? How much more investment do you expect over the next year? Obviously the subtext to that question is how much we might expect SG&A to grow next year or in 2023.
Thanks, Charles. We were very pleased to have achieved our target of doubling our customer-facing team, which we did in February of last month. That was a promise we made at the IPO. Obviously, that relates in to higher SG&A costs in the year. Now that we've established ourselves with a good commercial footprint, these costs will continue to grow, and there will definitely be more growth this year as we experience a full year of that commercial team we have in place.
However, the growth over time will be significantly less than the revenue growth and the margin growth we're planning, and that's why we believe we will be tracking towards our medium-term target of EBITDA breakeven. Looking at G&A, which is also related, this was our first full year of being a public company, and we put the necessary increases in infrastructure in place at the time of IPO. The G&A portion of SG&A is a fair reflection on where we expect those numbers to grow, and that should grow at a relatively modest rate as well.
We'll now take the next question from Odysseas from Berenberg. Please go ahead.
Hi, Tim. Hi, Gordon. Thanks for taking my question. First question, I want some additional color around the full year 2023 sales guidance downgrade and the softening of orders that you mentioned in the release. I understand that this was largely driven by a correction in COVID-related sequencing, perhaps from one month to another earlier in the year. Have recent product launches from competition, and in particular PacBio's Revio and Illumina Infinity played a role? What has been the customer or sales feedback you've been getting so far? Thank you.
You do the revenue and I'll do...
Okay. Okay. Thanks.
Competition.
Thanks Odysseas, just as a reminder of our LSRT guidance that we've just given, it's for 16%-30% growth on a constant currency basis. If you look at our underlying revenue growth during 2022, we achieved 30% level of growth. Indeed, if you look over the last few years, we've been tracking to those levels. In arriving at our guidance for this year, we've stripped it back to the underlying revenues, and we've assumed we will continue to grow in line with that growth rate that we've demonstrated we can consistently deliver.
As a reminder of 2022, it was a year of very strong Starter Pack growth. Those new customers that we've acquired are, we feel very confident are gonna drive the consumable revenues throughout this year. Looking at the higher end of the range that we've got, there's a number of large projects we're looking at. When we risk adjust those, that's how we've that's the reason for the wide range if that makes sense. Definitely COVID has been the major change that we've seen this year. Now we feel confident. COVID sequencing has now finished. That has caused us to really reflect on what our guidance levels should be. Order patterns continue this year, apart from COVID, in line with our expectations.
With regard to PacBio's Revio and Illumina's Infinity, my understanding is Illumina's Infinity is coming in around $1,000 to run a long read, and the read is relatively small when you think about what we can do, anything from 20 bases up to 1 million bases. I don't know what impact that will have. I mean, I think potentially, short-read sequencing customers will be able to look at some long reads and then will be very interested in it.
I think it might be quite useful to get the people who are very traditionalist SBS acolytes to open their minds up a little bit. PacBio's Revio, we'll see how that plays out in the marketplace. There's a lot of noise coming out from PacBio. We shall see how customers respond. We will continue to keep our heads down and focus on our own launches. Our Q20+ chemistry and P2 in particular, we think are both game changers. As well as, you know, with the Q20+ chemistry, accelerating adoption of PromethION, MinION, and GridION across the fleet.
That's all clear. On to my second one for Tim. I mean, impressive to see your gross margins expand here and targets unchanged in view of several downgrades across the sector. When we compare this to peers, do you think it's largely related to your different approach using materials which weren't as impacted by supply chain pressures, or have the manufacturing and design improvements ended up offsetting supply chain pressures more than you initially expected?
Thanks, Odysseas. Just as a reminder, I think it's an important point to make. Our margins in the first half of this year were 54.8%, our LSRT margins in the second half of the year grew by 300 basis points to 57.8%. When we look as we've been investing in improving our margins for a number of years right back to when we built our manufacturing facility in 2019. We have also been investing in our core suppliers in order to build those relationships over a number of years. We've been concentrating on increasing our in-house capabilities so that we can be more adaptable.
As an example, we've been able to switch components at a relatively short notice when some of the generic component supply chain shortages arose during the year. We've had that flexibility because of our in-house capabilities. We also benefit from carrying high inventory levels at the beginning of the year, and they're higher now. That was designed as a risk mitigation against an event such as this. I can promise you, we did not foresee everything that was gonna happen in 2022.
No. Clear. Thank you very much.
The next question comes from Paul Cuddon from Numis Securities.
Good afternoon, guys. I mean, just firstly for me, the new customer capture has been impressive during the year. I wonder if you could elaborate on the transition sort of between S1 and S2 customers and S2 to S3. Whether you're seeing an accelerating rate of capturing the user and then getting them to spend more on your kind of platforms.
There is some of that's not how this product is set up. A Ph.D. student may well do a Ph.D. in genetics and be a very strong S1 customer and then join you lot and become a banker. It's not, it's not meant to be an ever-increasing, you know, it's not like the MinION ultimately, and I'll keep saying this, like the mobile phone, will be ubiquitous eventually, and that is a massively important customer segment, and they come in and out. They don't necessarily have to transition to S2 and S3. Within cohorts, if we look at S2 for a moment, you look at public health laboratories, they're strong users of GridIONs, and they're not gonna move up to PromethION or down to MinION.
Unless of course there's a decentralized or point-of-care play, then they may well do. Generally, public health laboratories tend to be in centralized facilities. So it's not a continuum, and there is some migration. That PhD student chose not to go into investment banking, but decided to do a PhD, postdoc, become a professor. We have seen some customers, but I wouldn't say that is a strategy. That's just happenstance, and it's nice when it happens. They're, you know, they move all the way up. If you look at Miten Jain at Northeastern University now, formerly at Santa Cruz, he's now a power PromethION user. There is a continuum, but that's the exception rather than the rule. What will be interesting here is how P2 sits between those gaps.
I think rather than trying to move people from one continuum to another, we try to fill in the gap, hence Flongle the other way. The S2 will be very interesting because you can daisy chain it to be one or four or six or eight PromethIONs right up to filling the gap to 24. Watch this space. It's gonna be an interesting play, and we're very excited about P2.
Yeah. I mean,
Thanks, guys.
Just to add a couple more points to that. The strong growth in S2 customers of 26% growth in the number of active customers. Actually, I think it's mainly the way the math works within that. Companies do move in and out between S2, S3 in particular. The average revenues have stayed pretty much unchanged in the year. When you look at S3, we've, there has, we've added a net 17 customers in there.
The most of those customers have actually moved up from S2, and as they move up, they tend to pull the average revenue down because they're new to being an S3 and within the S3 group. If you look at the customers that were S3 customers at the beginning of in 2021 and were still S3 customers in 2022, we saw 18% growth in average revenue per customer to $898,000. I think that's a trend we would expect to continue as S3 will drive growth.
Yeah. I think that's a fair point. We're focused on reuse and utilization of boxes customers have. As Tim says, we do see S2, S3 migration, but the focus is utilization, and then it naturally happens rather than being a forced sale, if you like, or a forced fit.
Understood. Thank you. My second question was just on the kind of emerging battleground of kind of epigenetics and whether the nanopore kind of based approach has a better kind of dynamic range ability to detect more modifications than you can get using the, the more fluorescent and camera-based approach.
Sure. There was a landmark study last year, I think, publication that showed Oxford Nanopore can map 95%-98% of the methylome, as it's becoming referred to now. The current bisulfite methods are complicated. Sample prep is very long and laborious. They're error-prone, and all of those things add to the error budget on short-read sequencing by synthesis. Measuring directly the methylation in our platform as part of the sequencing offering is all part of the data analysis, the A100 upgrades that really allow us to power through all methylation. We are now seeing ever-increasing customers starting to map the whole of the methylome, and we think... I don't really think it's a battleground. I mean, we just know everybody will tell you that if you've got native methylation and full methylation with all CpG islands marked up, you would always pick that.
We're just at the beginning of enabling that on our platforms. I think this is going to be a huge market for us. It's clear from the GRAIL studies that the key and prominent driver of cancer is methylation. Everybody's known that for a while. What we provide is a comprehensive methylome, and we think that's game-changing. Our customers will provide that in publications and use cases.
Excellent. Thank you very much, guys.
As a reminder, to ask a question, please press star one. We'll take the next question from Zain Ebrahim from JP Morgan.
Hello, Zain Ebrahim, J.P. Morgan . Thank you for taking my questions. My first question would just be on population sequencing. You mentioned in the call that population sequencing is now around a third of S3 revenues in 2022. And it sounds like there may be a risk adjustment on population sequencing type contracts within the 2023 revenue guidance. What proportion of 2023 revenues in your guidance do you assume from population sequencing at the lower end of the guide versus the upper end? Can you provide an update on the contract wins you made in 2023 and how you're thinking about the evolution of population sequencing beyond 2024, when you see the expiry of the EGP contract?
Thanks, Zain. Yeah, there are a number of large contracts within our guidance. I'd, while some of them may be population genomics, they're in other areas as well, and Gordon talked about several new exciting areas that we're moving into. Excuse me. We risk adjust those opportunities. These are the opportunities. These are contracts we haven't won yet. We've always risk adjust those opportunities, and that really is the point I was making there is that's the difference between the lower end and the higher end of the guidance. Is there's a number of large contracts that we've risk adjusted down to get to the top high end of the guidance.
If you look at the EGP in particular, we just to remember what's happened. In November 2021, we signed a $68 million contract, which lasted for three years. Our guidance of GBP 15 million-GBP 20 million is based on the completion of that contract. Largely speaking, not significantly different from the cadence that we saw in the second half from the EGP in second half of 2022.
Okay. That's very clear. Thank you.
The next question comes from David Westenberg from Piper Sandler.
Hi. Thank you for your taking the question. I wanna continue with some of the question, prior question asked about kind of the S2, S1, S2 customer dynamics. Particularly wanna ask about maybe some of the trends with the introduction of the P2 and whether or not that might facilitate some of the customers that would have started at S1, maybe start immediately at S2, just given the fact that they have, you know, a instrument for to get more output in.
That's a great question, David. What was interesting when we put out the concept for P2, we got a lot of S1 customers, our MinION users, very interested in it. I think it may well. It'll definitely fill the gap between GridION and P24. That was kind of the design idea. You can daisy chain. You know, there was a lot of debate. Should we do an eight-channel PromethION? In the end, we've done the two-channel, and you can buy multiples. What's interesting is I think it is also going to catalyze, enable access for lower spend accounts to be able to do really, you know, punchy high throughput experiments. I think that, you know, just like the MinION has completely changed the market dynamics.
I think the P2 at the low end, I mean, it is $10,000, so it's still a fairly low entry point. I think we'll see growth that way as well. Yeah, it'll be interesting to see. Then in the middle there's gonna be, as you say, the median user, which probably will be in that sort of S2 spend. You know, it'll be an interesting one to see how it evolves. I think it might surprise us and be a bit more ubiquitous right across S3 accounts where people can do quick look C stuff, even though they can do that on a 24 or 48 channel. They tend to use particularly the large-scale projects. They tend to sort of have a PromethION set to run their human samples, and having a two-channel system to check kits, check assays, check sample prep may well be something that happens as well.
Got you. Thank you very much. Can you maybe talk about how the P2 might stack up, or how it might operate kind of on a competitive way? Do you see this as more adoption from other kind of long-read sequencers maybe that were using a service provider before for their long-read needs and now wanna bring it to the bench top? Or do you actually see the P2 being used in a semi-production mode from some of the service providers that also might, or is it, you know, maybe gonna do that maybe with the regular PromethION? Thank you very much, that's my second final question.
I think two things. We announced our automation solutions with Tecan, so that's quite important for those service providers to be able to get high throughput. Yes, I do think, you know, going from sort of nothing to a P24 is a big step. That's zero to Mach one. Having a service provider being able to buy two or four or six P2s and, you know, enter long read native DNA sequencing service provision with our automated solutions from Tecan will enable them to establish their market presence. I think this is a case where we were talking earlier about an S2 becoming an S3. They could well progress to a higher throughput as they get commercial traction.
I don't know if you saw this morning, Alexandre Wittenberg was talking about telomere-to-telomere comprehensive mapping of the tomato genome using nanopore only, and that's phenomenally important in crop insights as we start to think about that area. That is a nascent market that we can really go after, and the service providers can really enter it with a very low entry point to test the market, and we think, you know, that's gonna be an interesting customer segment for P2.
Thank you.
You know, on the ag bio side, the middle income countries, Africa, you know, we think this is gonna be really exciting around P2.
Thank you.
We will now take the next question from Veronika Dubajova from Citi. Please go ahead.
Hi, guys. Good afternoon. Two questions from me, please. One is, I'm gonna start with Tim, please, if that's okay. Just trying to understand the shape of the EBITDA in 2023, apologies, given the investments you've made into SG&A. Tim, I don't know if you can be a bit more specific. If we annualize out the hires that you've added in the second half of last year and obviously through to February, what should that, you know, give us as a baseline for SG&A for 2023?
Hi, Veronika. Thanks. Yeah. When you look at EBITDA, and just to say we adjust out positive and negative things that we considered not to be trends from adjusted EBITDA. For instance, this year we removed the GBP 51.8 million of COVID testing revenue, and we removed the profit from the sale and leaseback. It is designed to show a trend.
With the increase in revenues that we are planning, with the increase in margins that we are planning, there will be an increase in costs, the EBITDA should be roughly relatively flat. Maybe it may increase just a little bit during 2023. The trend after that, as the revenues grow, we benefit from the investment that we've been making over the last year or two, really should come through and reduce the EBITDA over the remaining years as we go towards breakeven. That should be a fairly constant upward trend or reduction in losses after that.
Excellent. That's very helpful. Thanks for that. My second question is for Gordon, and I'm just curious, Gordon, obviously we are already at the towards the end of March. Just curious if you've seen any change, COVID aside, any change in conversations you're having with customers year-to-date. Honing in particular on the S3 segment, the larger customers, do you have any visibility into what the funding's looking like through the remainder of 2023 and your degree of confidence in that? Thanks so much.
Yeah. I think two comments. Because of the CapEx-free model, we're not as exposed to cuts in government-funded spending. For us, some of those medium to large projects, they come after a small project. Small here is GBP 5,000-10,000. If you look at the NIH neurodegenerative study, that is starting to show some interesting correlations between structural variation as everybody expected, and that could then lead to a larger cohort. That is not just technology-dependent, it's also funding-dependent. We are seeing lots of opportunities for large-scale projects via small pilot-scale programs. That's our focus. You know, the weight-adjusted probability of winning those to become large substantial projects is where, as Tim said, the swing is in that sort of upper end of the revenue guidance.
There's a lot of exciting things going on, what the world looks like in 3 to 6 months as the data comes through, as the tender processes happen, and whether there is still money available to do bigger programs, that's all up in the air right now. You know, we're fairly confident that there are some important programs that we will do this year that if they do not bear fruition into larger contracts this year, will be setting us up nicely for 2024.
Understood. Very clear. Thank you both.
As there are no further questions, I will hand back over to Gordon Sanghera for closing remarks.
I'd like to thank you all for your time today. We'll be seeing some of you in briefings later this week and in subsequent weeks and on our road trips to the USA. I would just say we are one year in from our early launch of our Q20+ chemistry. Our P2 order book is fabulous, and we're really excited and well-poised to really push through. The other thing you may have seen this morning, recently, sorry, was Karen Miga doing telomere-to-telomere full genome on Nanopore only. A year ago, that was using multiple sequencing technologies, and that is really gives a sense of how we now provide the most comprehensive and complete genome, which will be really important as a reference atlas and as we talked earlier with methylation.
The real driver of revenue will be our Q20+ on simplex, which can meet all the accuracy criteria and small variant calling, but adds so much more biology. Ever increasingly, that is gaining huge momentum, and we think that will be a really, really big driver for our growth, and we will continue to innovate and iterate those chemistries to push the envelope further. Thanks for your time, everybody.