Michael W. Hunkapiller
Analyst · Morgan Stanley
Thanks, Trevin. Good afternoon, and thank you for joining us today. We are pleased with our fourth quarter results and the progress we've made throughout 2013 on driving our overall business. Highlights of our fourth quarter and full year results are as follows: We booked orders for 9 PacBio RS II systems in the fourth quarter, bringing our total bookings for the year to 25. This represents more than double the bookings we had in 2012. We installed 5 systems during the quarter, which brings our installed base up to 88 and our backlog of systems to 13 as of the end of December. Consumable revenue for the fourth quarter was $2.6 million, which was double that of Q4 2012 at $1.3 million and up 25% sequentially from our third quarter consumable revenue of $2.1 million, showing strong utilization in our installed base. You may recall during our last quarter's call that we were cautious about our fourth quarter consumable sales because we started out a bit slow due to the U.S. government shutdown. As it turned out, our business with U.S. government customers recovered, and we had strong growth among numerous other customers in the quarter. For the year, consumable revenues grew 84%, stemming from an increase in our installed base of about 25% and more significantly, by a greater than 50% increase in the average revenue pull-through per system. We are averaging well over $100,000 in consumable revenue per year per install system. Total revenue for the fourth quarter was $9.1 million, up 55% from the $5.9 million in Q4 2012. For the year, total revenue grew 8% from $26 million in 2012 to $28 million in 2013. Our development team did a terrific job delivering new products in 2013. Over the course of the year, we introduced a series of product enhancements that quadrupled the throughput of our system and greatly increased the read lengths achieved by our customers. With our latest chemistry release, customers have reported average read lengths in excess of 8,500 bases, and so their longest reads have exceeded 40,000 bases. In addition, we delivered significant enhancements to our software analysis toolkit, enabling customers to achieve the highest consensus accuracy with PacBio compared to all other sequencing technologies, including Sanger sequencing. This past year, PacBio became largely recognized as the gold standard for sequencing bacterial genomes and characterizing pathogenic strains of microbial organisms. Previously, we have described the 100K Pathogen Genome Project established by UC Davis, the FDA and other collaborators to create a database of food-borne disease-causing microbes, and that project has been progressing. In similar fashion, during the fourth quarter, Public Health England, the National Collection of Type Cultures and the Wellcome Trust Sanger Center announced a collaboration that will use PacBio's SMRT sequencing to fully sequence and finish a collection of 3,000 bacterial genome strains, which they expect to use as a reference for basic and clinical microbiology. That project is headed by Dr. Julian Parkhill, the head of Pathogen Genomics at the Wellcome Trust Sanger Institute and a highly regarded leader in the area of bacterial genomics. In the latter half of the year, we entered into a collaboration with Roche Diagnostics, the world leader in in-vitro diagnostics. In the short term, this agreement provided us with cash to further invest in developing our products in key applications. In the medium and long term, we believe this will enable us to capture a significant portion of the molecular diagnostics market as the provider of sequencing products to Roche. We've gotten off to a good start with Roche, working toward our common goal of creating products for the diagnostics market using our SMRT technology. Roche's sequencing unit is conveniently based in the San Francisco Bay Area, which makes it easy to have face-to-face communications. Our intent is to work on regulatory clearances in parallel with product development activities in order to be in position to sell products for this market as soon as possible. As we have mentioned previously, we believe initial regulatory clearances for our products could take 2 to 3 years. Finally, we ended the year with $113 million in cash, which is up $12 million from our cash balance at the end of 2012. Now I would like to provide highlights from 2 industry conferences we attended since our previous earnings call. The first is the American Society of Human Genetics conference that was held in Boston during late October. At the ASHG, we hosted a workshop featuring multiple presentations on structural variation studies with SMRT sequencing. As evidenced by the packed lecture room, the talks generated lots of interest and they did not disappoint. Dr. Evan Eichler of the University of Washington presented data from back sequencing in regions of the human genome that have previously been inaccessible to study, effectively with first- and second-generation sequencing tools, but which he is now able to study with SMRT sequencing. In his talk, Dr. Eichler expressed his excitement in having access to study the complex regions of human genomes at low cost and to recover areas that most genome studies have skipped over. He presented to a very full audience. We're clearly impressed with the data, and since then, we have seen momentum building in our business around human genome sequencing. Last month, we attended the annual Plant and Animal Genome conference that was held in San Diego. There were 15 program presentations and 19 posters featuring PacBio biotechnology this year, which is roughly double the number from last year. The presentations were wide-ranging from sequencing cash crops, such as spinach, lettuce and wheat, to the advanced study of model plant organisms such as Arabidopsis. There seemed to be an overriding theme to the presentations, which was the SMRT sequencing has been enabling researchers to reveal new areas of genomes, often discovering new genes and uncovering structural variations that have previously gone unnoticed because of the shortcomings in sequencing the short-read technologies. For example, in the presentation given by researchers from Ghent University, it describes how to use PacBio to sequence isoforms of the Spruce genome which they thought have been fairly well characterized by high coverage Illumina sequencing. They were surprised to find 2,000 unique protein-coding genes from the PacBio analysis. In another study, researchers at the Salk Institute described their findings from sequencing strains at the model organism, Arabidopsis, with PacBio. When compared against short-read sequence data, the PacBio data revealed that 1/3 of the single nucleotide polymorphisms or snips present in the strains were missing from the short-read data. Studies such as these are raising interest in the agricultural area because of the significant ramifications of missing large chunks of data when trying to determine the markers for important crop traits such as those for disease and drought resistance. Concurrent with the PAG conference, we worked with Dr. Casey Bergman from the University of Manchester, Dr. Susan Celniker and Roger Hoskins at Lawrence Berkeley National Laboratory and Dr. Sergey Koren and Adam Phillippy at the University of Maryland to post new data sets on the assembly of the model organism Drosophila, a fruit fly, using SMRT sequencing. Model organisms can be the best, fastest and most effective way to advance science, especially when human experimentation may not be feasible, and Drosophila has been used to study genetics for decades. This new data set for Drosophila using PacBio technology represents a dramatic advancement for researchers, significantly improving the assembly of this genome by filling in regions of sequence missing in reference genome. For example, chromosome 3L was reduced from 22 contigs or fragments down to just a single contig, meaning that this chromosome are almost fully assembled with no gaps using the PacBio data alone. This level of completeness in the de novo assembly is unprecedented in the metazoan genome. To put this in perspective, the reference genome for Drosophila, known as Release 5, has been over 15 years in the making. With experts utilizing Sanger sequencing, short-read sequencing, RNA transcript sequencing, back clones and numerous labor-intensive techniques to achieve what is considered a high-quality genome, the PacBio technology, a few researchers needed just 6 weeks from collecting the sample to completing a considerably higher-quality assembly. Dr. Celniker, who is regarded by many as the foremost expert of the Drosophila genome, commented that the PacBio assembly was a huge improvement over the reference, and she was particularly impressed with PacBio's ability to piece together regions of the genome that have thus far been a mystery such as the Y chromosome. This data set has also been made publicly available, and we believe this will lead to a flurry of new research in this important area. As a footnote, about 2 weeks ago, a group of researchers posted their latest results of sequencing and assembling Drosophila using so-called synthetic long-read technology as an adjunct to standard short-read methods. Their results suggest some improvement with this approach relative to using standard short-reads alone. However, they were nowhere near those obtained with SMRT sequencing. The PacBio assembly left far fewer gaps at 128 contigs for SMRT sequencing versus more than 5,000 with the synthetic long-reads. N50, which measures the length of the contig for which half of the total assembly is contained in contigs of that size are larger, was remarkably better in the PacBio assembly. 15 megabases versus 0.1 megabase, a 150-fold improvement. Now shifting to publications. The rate of customer publications with SMRT technology continues to increase. On a cumulative basis, we've been over 100 publications, up from about 20 a year ago. I'd like to highlight some recent publications focused on an emerging application for us: isoform sequencing for transcriptome analysis. The first paper I'll highlight appeared in the Proceedings of the National Academy of Sciences, or PNAS, entitled Characterization of the Human Embryonic Stem Cell's Transcriptome by Hybrid Sequencing, written by a group at Stanford. In the paper, the authors provide background by describing a problem they see with previous and ongoing RNA-Seq studies, which is the inability to capture full-length mRNA isoforms by using reads of just a few hundred-base pairs. The authors write, "We are still far from achieving the original goals of RNA-Seq analysis, namely the de novo discovery of genes, the assembly of gene isoforms, and the accurate estimation of transcript abundance at the gene or isoform level." Isoform detection or prediction with short-reads is even more difficult when the full set of possible isoforms is not known going into the project. The authors then described their own RNA-Seq experiment utilizing PacBio data to examine the human embryonic stem cells which were thought to be well characterized in numerous previous studies. Surprisingly, over 1/3 of the RNA transcripts the researchers detected were novel isoforms that were previously unidentified or missing from all previous studies. The authors concluded that these results suggest that gene identification, even in well-characterized cell lines and tissues, is far from complete. Another paper on this topic was published recently in Nature Methods, entitled Assessment of Transcript Reconstruction Methods for RNA-Seq, written by researchers from the European Molecular Biology Laboratory. In the paper, the authors described that "the complexity of higher eukaryotic genomes imposes severe limitations on transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation RNA-seq data." To address these limitations, the authors conclude that "ultimately, the evolution of RNA-seq will move toward single-pass determination of intact transcripts. Third-generation instruments will realize that potential and inspire new computing approaches to meet the next wave of innovation in transcriptome analysis." Now turning to our product roadmap. This is a good lead-in to describing the papers, our product and technology roadmap for this coming year. With growing interest in using SMRT sequencing for the analysis of full length transcripts and alternative splicing isoforms, we plan on releasing software in the first half of this year for streamlining these experiments. We call this application IsoSeq, which is short for isoform sequencing. Additional software enhancements planned for this year include enhanced detection of viral minor-variants in genome examples, improvements to long-amplicon haplotype analysis to benefit applications such as HLA analysis and continue the advancements in assembly algorithms for applications such as diploid de novo assembly. In the area of sample preparation, we will provide new protocols and reagent kits for automated library preparation methods on liquid-handling robots such as Agilent's Bravo and PerkinElmer's Sciclone workstations. We are also continuing to improve methods to better ensure the integrity of long DNA inserts, so users can take better advantage of the PacBio reads that are 20 kilobases and longer. With regard to read length, I mentioned earlier that customers have reported average read lengths in excess of 8,500 bases with our P5-C3 chemistry. We are continually driving improvements in read length through a combination of sample prep improvement, software enhancements and new chemistries. Our goal over the next 2 years is to increase the average read length to 20,000 bases. Keep in mind that the longest reads reported today are already in excess of 40,000 bases, and we should obviously expect that to increase as well. Finally, we plan on continuing our rapid pace of increasing the throughput capabilities of the PacBio system. In each of the past 2 years, we have increased throughput of the PacBio RS system by a factor of 4. Our target for this year is to once again increase it by a factor of 4. We have several ways to accomplish this. First, as I just mentioned, we can increase the average read length through continued improvements in chemistry. Second, we can increase the number of active wells in the SMRT cell. Currently, about 1/3 of the 150,000 wells on a SMRT cell are generating useful data because the current loading of enzymes in the well stems for process which follows a plus-on distribution that limits the maximum number of singly loaded wells to about 55,000. We are working on techniques for improving the loading efficiency of the SMRT cell beyond this distribution. Lastly, as I mentioned earlier, we are working on methods for improving the quality of DNA in the sample preparation process. The input quality of DNA has a direct effect on sequencing read length and throughput. None of these throughput improvements should require hardware changes to the PacBio RS II systems. Now I'd like to provide a few comments on the markets and applications we're addressing. Recent publications and customer presentations at industry conferences like the ASHG, PAG and AGBT have been raising awareness of the high value we bring to a variety of applications for SMRT sequencing. At last month's JPMorgan Healthcare Conference, we describe how we initially focused on sequencing DNA from isolated bacteria and demonstrated the high value of SMRT sequencing in that area. Over the past year and even more so over the past 6 months, we have demonstrated the value the SMRT sequencing brings to in areas such as metagenomics for studying the human microbio and the value it brings to direct human sequencing for studying portions of the human genome that have proven to be unsequenceable by other methods. We are still very early in driving on these markets, but we're seeing signs it's making a difference in our sales pipeline. Finally, I would like to mention that we are looking forward to hearing from many of our customers at next week's AGBT meeting in Marco Island. There are 9 schedule podium presentations featuring PacBio at this year's conference, up from 5 last year, and 29 posters this year compared to 19 last year. We will also be hosting a workshop on Friday at the conference where we'll be sharing some of our latest application developments, including IsoSeq, PacBio's solution for analyzing full-length transcripts. That concludes my remarks, and I'll turn the call over to Susan.