AbCellera Biologics (ABCL 1.38%)
Q1 2023 Earnings Call
May 04, 2023, 5:00 p.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good afternoon and welcome to AbCellera first-quarter 2023 business update conference call. My name is Terry, and I will facilitate the audio portion of today's interactive broadcast. [Operator instructions] At this time, I would like to turn the call over to Tryn Stimart, AbCellera's chief legal and compliance officer. Please go ahead.
Tryn Stimart -- Chief Legal Officer and Chief Compliance Officer
Thank you. Good afternoon and welcome to AbCellera's first-quarter 2023 business update. We're pleased to have you with us today as we discuss the results announced in our press release issued after the market closes today, which you can find on our Investor Relations website. With me on the call today are Dr.
Carl Hansen, AbCellera's chief executive officer and president; and Andrew Booth, AbCellera's chief financial officer. The webcast portion of this call contains a slide presentation that we will refer to during the call. If you are following along on the phone and wish to access the slide portion of this presentation, you may do so on the Investor Relations section of our website. For those of you who have access to streaming portion of the webcast, please be aware that there may be a delay and that you will not be able to pose questions via the web.
This presentation may contain forward-looking statements pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on management's current expectations and are subject to certain risks and uncertainties. Please review our SEC filings for risk factors that could impact our future performance. Our presentation and SEC filings are available on our Investor Relations website.
Note that all dollars referred to during our call today are U.S. dollars. Now, I am pleased to turn the call over to Dr. Carl Hansen.
Carl Hansen -- President and Chief Executive Officer
Thank you, Tryn, and thanks, everyone, for joining us today. It's my pleasure to provide an update on our business for the first quarter of 2023. Through the first quarter, we continue to allocate our resources to the execution of our long-term strategy, investing in building teams, technology, and infrastructure to create the industry's preferred engine for antibody therapeutics and using this engine with partners to develop a diversified portfolio of stakes in future antibody therapies. This is a long-term strategy designed to create an increasing competitive advantage to maximize value creation and to mitigate the risk that is inherent in drug development.
We continue to make progress on both objectives of our strategy. With respect to our engine, at the front end, from program launch to lead candidate generation, I believe we now have capabilities that are unmatched in the industry and that continue to improve. At the middle of our engine, over the past 12 months, we have brought online a set of powerful new technologies and workflows for antibody engineering, high throughput assessment of drug-like properties, and lead optimization. These capabilities are now being deployed in partnered and prepartnered programs and enable us to move programs quickly from idea right through to final drug candidate.
A major focus is now on building the back end of our platform, including drug manufacturing and regulatory capabilities. We're making good progress in recruiting the leadership to these efforts and are actively building the labs and facilities that are needed for these functions. I'm confident we are on track and believe these efforts will -- will prove highly valuable to our partners and will provide AbCellera a major strategic advantage to all dimensions of our business. Underpinning our workflows, we continue to invest in the automation and software systems that are critical to integration, efficiency, and scale and that are the foundation for the development and deployment of machine learning methods.
In terms of building our portfolio, we continue to prioritize programs that maximize long-term shareholder value and not near-term cash flow or volume of partnerships. With the technology, the teams, and the infrastructure in place, perhaps the most valuable input for adding value to our portfolio are the new ideas for medicines. We believe that good ideas can come from anywhere. For the large majority of our programs, ideas come from our partners.
Our partners come to us because we can help them get to their next value inflection point with greater certainty, speed, and capital efficiency. Depending on the resources and program requirements, these collaborations contribute to programs -- contribute programs to our portfolio that can be structured with different risk-reward profiles, including partner-initiated discovery programs and co-development programs. Another rich source of program ideas are antibody development problems that are widely known in the industry but that are generally believed to be unsolvable. We invest in sustained technology development efforts that seek to unlock these high-value opportunities.
This requires working on multiple targets. As this work proceeds, these prepartnered programs can generate wholly owned assets that anticipate partner needs. Although these programs represent a small fraction of our portfolio, they have the potential to create the most value on a program-by-program basis when partnered. Moreover, success in our prepartnered work will demonstrate that our -- our strategy is working and that our technology can open up new market opportunities, thereby attracting more program ideas from partners.
Regardless of the source of the idea and regardless of the program type, all programs are ultimately handed to partners. Each contributes to building a large portfolio that is diversified across partners, risk-reward profiles, modalities, and indications. Being open to working on the best possible ideas regardless of the source allows our engine to create maximum value for shareholders, partners, and patients. T Cell engager, or TCEs, provide a specific example of how our prepartnered programs arise from technology development work that has the potential to open up new areas and make us a preferred partner for an entire class.
TCEs are among the most promising new modalities in cancer therapy. First proven effective in liquid tumors, recent clinical data supports the potential of TCEs in treating a wide array of solid tumor types. T cell engagers are antibodies with two arms that are designed to simultaneously bind to cancer cells and specific immune cells called T cells. TCEs work by bringing T cells and cancer cells together and stimulating the T cells to kill the cancer cells.
Two key challenges, both associated with toxic side effects, must be overcome to realize the full potential of TCEs in treating cancer. The first challenge is to achieve the appropriate strength of T cell activation. Activation that is too low results in poor efficacy, while overstimulating T cells can result in cytokine release syndrome, a systemic inflammatory response that can limit treatment and result in severe or life-threatening toxicity. The second challenge with TCEs is specificity, that is to generate antibodies that recognize targets that are present only on cancer cells and that are not present on healthy cells.
In April, AbCellera presented two posters at the 2023 American Association for Cancer Research meeting that demonstrate how our TCE platform can address both of these challenges. Today, I would like to highlight the main findings from this work. With respect to the first challenge that of controlling the level of cell activation, the level of activation is determined by the bispecific format as well as the properties and pairing of the source antibodies. The vast majority of tissues activate T cells by binding to a protein called CD3.
Because CD3 is a notoriously difficult target, there are very few accessible CD3 antibodies from which to make bispecifics. This limits the ability to control the level of T cell activation. In fact, approximately three-quarters of TCEs in the clinic are derived from a single mouse CD3 antibody, SP34-2, that was discovered in the 1980s and has suboptimal properties, including the induction of strong cytokine release. To solve this challenge, we launched a technology development project about 18 months ago to build a platform that could quickly generate TCEs that achieve the optimal balance between tumor cell killing and cytokine release.
Our hypothesis was that there is no single CD3 that is well suited for every application and that a large and diverse panel of CD3 is an essential resource for creating TCEs with superior properties. One of our posters at AACR demonstrated data on our newly generated CD3 panel and its use in building optimized TCEs against two cancer targets: EGFR and PSMA. Key results from this poster as are as follows. First, we have built what we believe to be, by far, the industry's largest collection of CD3 binders with more than 500 unique antibodies.
This panel offers unmatched diversity of binding properties and binding locations, excellent developability, and is highly differentiated from commonly used molecules. Second, this panel allowed us to effectively control T cell activation against both targets and to achieve the desired profile of potent tumor cell killing with low cytokine release. Third, in all cases, the resulting TCEs had superior properties as compared to those built with the commonly used SP34-2 CD3 binder. And fourth, that the performance of different TCEs depends on the tumor target and the level of target expression on the cancer cells.
Together, these results support our hypothesis and demonstrate the potential of our platform to quickly generate TCEs that are engineered to have optimal properties. In our second poster, we presented an approach to addressing the second challenge of finding antibodies that are highly specific to cancer cells. Central to this challenge is that there are few known proteins that are expressed only on the surface of cancer cells and not on the surface of healthy cells. Because there are many more cancer-specific proteins expressed inside cancer cells, the ability to target these with antibodies would open up a huge number of potential targets.
One way of doing this is to target fragments of cancer proteins, known as peptides, that are naturally presented at the surface of cancer cells by the major histocompatibility complex, or MHC. This process of peptide presentation by MHC is a part of natural immune surveillance and occurs in all cell types in the body. The potential of targeting cancer through MHC peptides has attracted high interest and is being pursued with different approaches, most commonly with cell therapies or engineered T cell receptors, or called TCRS. An alternative approach is to use antibodies, known as TCR mimetics, that are highly specific to MHC peptide complexes.
Discovering such antibodies is extremely challenging, and to date, there are only two examples that have made it into clinical development. Our poster demonstrated that we can quickly generate antibodies against a well-validated cancer-specific MHC peptide target derived from the protein, MAGE-A4, for which there has been a clinical-stage TCR mimetic. We screened more than a million cells and found more than a dozen fully human antibodies with high affinity, good developability, and specificity to MAGE-A4 that is comparable or superior to the clinical benchmark. Perhaps most significant is the speed and ease with which this result was obtained from a single screening campaign and without the need for subsequent antibody engineering.
This result shows that we have capabilities that can readily address a large and essentially untouched class of tumor targets for TCEs. Importantly, TCR mimetic antibodies can also be used in other therapeutic modalities, including antibody drug conjugates, radiopharmaceuticals, and cell therapy. As such, we believe this is a technological advance that has broad implications for precision oncology. Another area we are focused on is unlocking difficult membrane protein targets.
I am pleased to share that we had a new molecule to enter the clinic this quarter against this challenging target class. This program is from one of AbCellera's first discovery partnership agreements with Teva Pharmaceuticals and is directed against a difficult membrane protein target for an undisclosed indication. I would like to congratulate Teva on this milestone, and we are pleased to see the work from this collaboration progressing forward to help patients. As I've mentioned on previous calls, AbCellera's discovery engine and business model can also help to expand the ecosystem of drug developers by leveling the playing field for innovative new ventures.
Again, this is about finding the best ideas and the best innovators and connecting them with technology to create new opportunities and, in some cases, new companies that might not otherwise be possible. This quarter, we are pleased to congratulate our partner, Abdera, who announced last month a $142 million financing. Abdera's proprietary technology develops next-generation radiopharmaceuticals to treat cancer. AbCellera was a founding partner in Abdera, and we started our first program with them in March of 2021.
Abdera has announced that they have elected the first clinical candidate from this program, a radiopharmaceutical for the treatment of cancer. The company plans to file an IND in 2024. It's worth emphasizing the remarkable speed by which this company has gone from concept to high-growth biotech with their first clinical candidate, a growing pipeline, and backing by top-tier investors. AbCellera -- pardon me, sorry -- finishing up, AbCellera is now in a position of enviable strength.
We have a strong balance sheet and remain focused on the fundamentals of our long-term strategy. Accordingly, we are directing our energy and capital to three key activities: first, expanding the capabilities of our discovery engine, including forward integration with manufacturing, regulatory, and clinical capabilities; continuing our technology development efforts to unlock new target classes and modalities, including T-cell engagers, GPCRs, and ion channels; and advancing high-quality programs and partnerships to build our portfolio. We believe continuous work and progress against these priorities will create the maximum long-term value while minimizing risk. This quarter, we have brought evidence that the strategy is working in the form of a new molecule in the clinic, the co-founding and financing of an exciting new company in the area of radiopharmaceuticals, and data showing that our engine can solve key problems in developing new T cell engagers for the treatment of cancer.
We look -- we look forward to sharing more evidence of progress later this year with anticipated milestones, including election of the first clinical candidates from partner-initiated co-development and prepartnered programs. And with that, I will hand it over to AbCellera to discuss our financials -- I'll hand it over to Andrew to discuss our financials. Andrew.
Andrew Booth -- Chief Financial Officer
Thanks, Carl. First, let me highlight progress made in our key business metrics in the first quarter of 2023. We ended Q1 with a cumulative total of 101 program starts. There were no new program starts in the quarter.
As a reminder, the number of starts in any given quarter will be irregular. Over the trailing 12 months, we have started to work on 17 program, representing almost a fifth of our cumulative number of program starts. We expect that the long-term trend on program starts will remain solid while we continue to do more work and add more value on programs. We signed three new programs under contract with one new partner, RQ Bio, in the quarter.
We ended the first quarter of 2023 with 177 programs under contract with 41 unique partners. As we mentioned on the last call, the numbers included in our key business metrics do not include prepartnered programs from our technology development efforts. For our molecules at the clinical stage, we saw one additional molecule from a discovery partnership reached the clinic, progressing into phase 1 clinical trials. This new molecule brings our total number of molecules in the clinic to nine.
The new molecule was discovered by us in partnership with Teva and has entered clinical trials with an indication in neuroscience. As we have said in the past, we view our growing list of molecules in the clinic as specific examples of our near and mid-term potential revenue from downstream milestone fees and long-term royalty payments. Turning to revenue. Revenue in the quarter was approximately $12 million.
This is our first full quarter without COVID royalty revenues since the FDA announced in Q4 of 2022 that bebtelovimab is no longer authorized for emergency use. Revenue this quarter was driven by approximately $11 million in research fees relating to work on partner-initiated discovery programs, compared to approximately $9 million in Q1 of 2022. This quarter's revenues also include approximately $1 million in milestone payments attributable to molecules progressing into the clinic, both from the partnership with Teva and from NovaRock, which progressed into the clinic in late 2022. We also generated approximately a half a million dollars in licensing fees.
Turning to our operating expenses. Our research and development expenses for the third quarter were approximately $53 million, representing a roughly $26 million increase over the same period of the previous year. This increase reflects the continued growth of our program execution work, platform development, and forward integration to build the capabilities and capacity of our engine. It also includes investment in partnered and prepartnered programs.
Approximately $20 million in the first quarter related to specific one-time and nonrecurring upfront investments in co-development and prepartnered programs. And sales and marketing expenses for the quarter were approximately $4 million, compared to approximately $2 million in Q1 of 2022. This increase reflects continuing investments in our business development efforts and team. General and administration expenses were relatively flat for the quarter at approximately $15 million, compared to approximately $14 million in Q1 of 2022.
This increase shows some operating leverage in the G&A investments that we have made so far to support the growth of our business. Looking at earnings, we are reporting a net loss of roughly $40 million. This compares to net earnings of approximately $169 million in Q1 of 2022. The loss reflects our continued investments in our business and the absence of royalty revenues that were present in Q1 of 2022.
In terms of earnings per share, this quarter's result works out to a loss of $0.14 per share on a basic and diluted basis. Looking at cash flows. Operating activities for the first three months of 2023 used roughly $44 million. This is our first quarter of negative cash flow since becoming a publicly traded operating company.
In the absence of regular royalty revenues, we would expect our quarterly operating cash flow to be irregular and often negative as we continue to invest in the company. As a part of our Treasury strategy, we keep over $600 million invested in short-term marketable securities. Our investment activities for the first three months of the year include an approximately $98 million net increase in these holdings as a part of that cash management strategy. All other investment activities amounted to approximately $51 million, including nearly $15 million invested in property, plant, and equipment and approximately $35 million in long-term investments.
Altogether, we finished the quarter with over $800 million of cash, cash equivalents, and marketable securities. We prioritize investments to achieve scale, operating leverage, and expected rates of return when we allocate capital. As a reminder, we have also been successful at finding nondilutive sources of capital including government funding. As an example, we have received funding commitments from the Government of Canada's Strategic Innovation Fund to support expansion into our manufacturing facility.
While this capital does not show up on our balance sheet, it allows us to maintain a high level of capital efficiency. With respect to our operating expenditures, our capital needs are very manageable, and we remain in a strong liquidity position that allows us to fully execute on our strategy with excellent visibility and runway. We continue to believe that we have sufficient liquidity to fund well beyond the next three years of investment and growth. And with that, we'll be happy to take your questions.
Operator?
Questions & Answers:
Operator
Thank you. [Operator instructions] The first question on the line comes from Andrea Tan of Goldman Sachs. Please go ahead. Your line is open.
Andrea Tan -- Goldman Sachs -- Analyst
Thanks for taking my question. Carl, could you maybe speak more on the feedback from the AACR poster presentation? And then, when you do think about the panel of the CD3 antibodies that you've built, what are the next steps here?
Carl Hansen -- President and Chief Executive Officer
Thanks, Andrea. So, we had, I'd say, a terrific response from the presentation of the data at AACR. There were several, you know, conversations that have since moved forward with some of the top firms that are working in this space. Generally, I'd say the people that have been working in this space for a long time fully appreciate the scale of what has been done in expanding the diversity and the quality of CD3 antibodies that we have started in place.
And the early data that we presented demonstrating that we could use this to tune the level of T cell activation while still getting tumor cell killing attract a lot of attention. So, we are advancing those -- those discussions. There are some groups that are particularly interested in the prepartnered programs that have begun. These are still at an early state, but we do expect that we will continue to work on those over the next year and move some of them to the point of development candidate where we're starting to narrow in on final clinical candidates.
We expect that that will have a couple of positive impacts. One, it allows us to further demonstrate the versatility of the platform across multiple targets and to move these forward into molecules that have the properties that are suitable to move into IND-enabling studies. And two, it is a way to engage with some of the companies that are more interested in assets than in access to the capability. And at the same time, you know, the capabilities we've shown have also started to generate quite an interest from firms that want to start on new -- on new targets and begin from the beginning.
So, I would say this is on track. We believe that this effort is creating value, and it's still a little early to project just when we'll be able to engage with one of those -- one of those conversations or more that's ongoing.
Andrea Tan -- Goldman Sachs -- Analyst
Understood. And then, my second question is, just as you think about your stated goal of speeding up the time from ideation to moving a candidate into the clinic, just curious now that you have nine molecules in the clinic, first, can you help quantify where you think you are right now in terms of the average time in between those -- those two points? And then, second, how much quicker do you think you can get as the technology and the platform improve?
Carl Hansen -- President and Chief Executive Officer
Yeah, that's a tough question to answer. So, you know, we have nine molecules in the clinic. Some of these have come from the tRNA platform. Others have come from discovery work that we did and have moved forward with partners now into early clinical development.
When you look at the molecules in the clinic, this is always a trailing metric. So, what you see coming to the clinic today is work that was done years ago at a time when we were a smaller company and we were handing off molecules in an earlier state. So, we are very pleased to see that even some of the earliest work, for instance, what was mentioned today from Teva, that's a program that wrapped up in 2017, made it through to the clinic and shows that there is early work that, despite the fact it didn't get quickly to the clinic or in a timely way, is not dead and continues to move forward. But the more recent projects, you know, we think that from programs start to clinical -- to an IND filing in roughly three years is -- is very quick compared to the industry standard and something that we expect to be happening.
So, we're making progress there. In terms of how quick we think we can be, we think that really comes together once we have finished off the back end of the platform here at AbCellera. So, if we have integrated translational science, manufacturing, and regulatory capabilities, then we can save a lot of time through the integration and the streamlining. And so, that's -- that's something that we're working on hard, but of course, that's yet in the future.
Andrea Tan -- Goldman Sachs -- Analyst
Perfect. Thanks so much.
Operator
The next question on the line comes from Antonia Borovina of Bloom Burton. Please go ahead. Your line is open.
Antonia Borovina -- Bloom Burton -- Analyst
Hi, guys. Thanks for taking my questions. So, my first question is regarding Abdera. Can you just remind us what your current economic interest is in the company? And you classify this as a partner-initiated program? But just wondering, considering that you were one of the founders, are you doing any more work on this program, or are the deal terms kind of pretty similar to what we've seen with the other partner-initiated?
Andrew Booth -- Chief Financial Officer
Hey, Antonia, this is Andrew. I'm happy to take that one. Yeah, we were a founding partner, as Carl mentioned in the prepared remarks, back in 2021 with Abdera. And we announced that with that partnership that we would do the discovery for them.
We took a minority. So, less than -- and continue today to have a minority equity position in the company that's less than much less than 20% and, in addition, have the typical kind of deal with the milestones and royalties due on the molecules that we discover in our partnership with them. Those are included in the metrics that we propose or that we publish every year in our 10-K. So, they're included in those aggregate metrics that are published.
What's important there, and it's maybe points to some comments that Carl made in the first question, that those molecules look to be on track to get from that idea to the clinic within about three years. And -- and that was a partnership of nine molecules. So, we continue to do work with them on some of those additional targets. And of course, the first ones in discovery work that we've done on their first antibodies have been completed and handed back to them and then are on track to get into the clinic in 2024.
Antonia Borovina -- Bloom Burton -- Analyst
OK, great. And then, my additional question is just regarding the sector downturn. Are you seeing anything with regards to the inbound interest from potential partners, the type of deal structures partners are interested in, or maybe anything from the competitive landscape, like, is there more competition for partners or consolidation in the field?
Carl Hansen -- President and Chief Executive Officer
Yeah, sure -- excuse me -- Carl Hansen. I'll take the question. So, this is something that obviously we're watching and responding to as everyone else's From our perspective, you know, the big change in -- in our partnership business has been really focusing on finding the very highest-quality partnerships and engaging in partnerships with -- with a deeper interaction in terms of bringing molecules further to a value inflection into clinical development. So, over the past, you know, year of focusing on that, our feeling is that, despite the economic environment, the quality of the partnerships, the quality of the work that's being done, and the volume and amount of work that is being done across programs have all gotten substantially better.
And so, we feel like our business is getting stronger over time. It's definitely the case that there's a lot of companies that are facing, you know, difficult headwinds in terms of raising capital. When it comes to competitors, we see that as a strategic advantage for AbCellera given that we're well positioned, well capitalized, and we can just focus on executing on the plan. With respect to potential partners, there is the possibility that companies are forced to prioritize on a smaller number of programs.
It's up to us and our business development teams to make sure that we're finding those opportunities and engaging on the things that are highest priority in this market and in any market. And so, we -- we don't feel we're highly affected. But of course, it's -- you know, it's still playing out. And so, we'll -- we'll keep our eye on that.
Antonia Borovina -- Bloom Burton -- Analyst
OK, thanks.
Operator
The next question on the line comes from Stephen Willey of Stifel. Please go ahead. Your line is open.
Steve Willey -- Stifel Financial Corp. -- Analyst
Yeah, good afternoon. Thanks for taking the questions. I guess, on the -- on the TCE front, do you think that some of the CD3-focused collaborations that you could be doing here going forward would include scenarios where a partner is kind of bringing a variable domain against the tumor antigen to the table and just selecting one of the CD3 variants to pair with? Or do you envision, I guess, monetizing the CD3 library by kind of a build-for-purpose, start-from-scratch type of approach where you're developing both -- both ends of the antibody?
Carl Hansen -- President and Chief Executive Officer
Yeah, the short answer is that we're open to working with partners in whatever way makes the most sense. So, you know, the three ways that we envision partnerships being set up are, you know, first, we have now initiated work on five prepartnered programs. As those advance, we expect that there will be partners that are interested in those specific targets, and that will be -- and we'll be able to partner with them either while we're still in development and getting toward the final candidates or after that has been done. So, that's the first way.
The second way is that, by doing that work, we have the data to show partners the ability to quickly generate optimized TCEs. And this has attracted interest from groups that have new targets for which they don't yet have antibodies. And of course, our business and our capabilities allow us to quickly generate those antibodies and then pair them and test them with different CD3. So, that's the second way.
And the third way is the one that you alluded to where partners may have binders already that they believe are adequate or up to the task for making a new TCE. We would be happy and, you know, are interested in engaging and using our CD3 panels to properly pair those with the right binder to get the right properties. That isn't just a matter of, you know, sending over CD3s. It requires that we take the binding molecule and we make a large panel of bispecific and run it through the functional assays.
And there may even be a couple iterations of that since we have a very large panel to go through. So, there's still substantial work there, but that's -- that's another path forward and one that we're definitely contemplating, and there are some discussions in that direction.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK, and then, I know one of the AACR posters highlighted the capacity on the MAGE-A4 forefront to target these MHC peptide complexes, and I guess that's addressing the specificity part of the question, which is kind of plague TCEs in solid tumors. But then, there's also this question, I guess, of, you know, intra-tumor T-cell availability and, I guess, energy that exists in solid tumors as well. And -- and just curious if in doing more work here on -- on -- on the TCEs, if you're now, I guess, inherently interested in moving toward a multispecific format as well where you're introducing something like co-stimulation?
Carl Hansen -- President and Chief Executive Officer
Well, you know, first off, bispecifics or multispecifics are an area that we believe is going to be very high growth for the industry and one that we're very well positioned to help drive. Our work to date has been on TCEs that are based on, you know, a variety of formats using OrthoMab that are pairing CD3 with tumor antigens. You're right to bring up, you know, some -- some questions of T cell energy or the T cells there. One of the things that we expect is that some of these therapies would be used in combination with other immunostimulatory or checkpoint inhibitor-type therapies, and that's something that is being pursued across the industry.
So, you know, that's -- that's one of the solutions. But coming back to your opening comment, you know, the work against MHC peptide antigens, we think, is -- you know, is showing the potential of the platform to open up a whole field of targets for TCEs and, even more broadly, to open up the target space for precision oncology. And so, we think that particular, you know, result and, particularly, the speed and ease with which it was done, is very significant and has potentials in ADCs and radioisotopes and beyond. So, that's an area that we're -- we're quite excited about and, you know -- and are starting to -- to work on a strategy as to how we want to pursue that further on the technology front and the partnership front.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK, that makes sense. And then, maybe just lastly for Andrew. Can -- can you clarify just a little bit more the -- I guess it was about 20 million of one-time impact that was embedded in R&D as a function of investment in partnered and prepartnered programs. Are those specific to any collaboration or [Inaudible].
Andrew Booth -- Chief Financial Officer
Yeah, it's a great question, Steve. So, yeah, absolutely. So, as we've mentioned, we've got -- and as you know from our previous metrics, we've got a number of co-invest programs and prepartnered programs that we've initiated. The good news there is that those programs are progressing well.
And as Carl even said, we expect at the end of the year to have something to talk about in terms of lead clinical candidates in those areas. We have some upfront investments or commitments we needed to make in regard -- specifically related to those co-invest and programs, and that's what needed to go through our P&L in the R&D and the form of 20 million. So, we don't expect it to be recurring. It's one reason we called it out, so we know you're building your models and just to make sure you have the right kind of run rate R&D expense built into those models.
We wanted to call out that upfront investment specifically and hope to have more to share about that at the end of the year with, as Carl mentioned, having lead candidates or clinical candidates available to talk about.
Steve Willey -- Stifel Financial Corp. -- Analyst
OK, appreciate it. Thanks.
Operator
The next question on the line comes from Nishant Gandhi of Truist. Please go ahead. Your line is open.
Nishant Gandhi -- Truist Securities -- Analyst
Hi, this is Nishant. I'm on for Robyn, actually. So, our first question is in terms of BD, how much of your current business development in -- is from inbound versus, like, the levels of marketing that you kind of have to do for this?
Carl Hansen -- President and Chief Executive Officer
Sure, I'll take that. So, you know, the nature of our business development is that it depends a great deal upon building scientific credibility and a network across the industry. So, you know, the -- the best opportunities that we find are typically because we have become known -- known in the sector through investors, through stakeholders, through previous partners, and of course, at scientific conferences. So, I'm not sure if you want to call that marketing or if you want to call that inbound.
It's really about building relationships and trying to find the right people within organizations that appreciate the technology and can see how AbCellera's platform can help to create value on both sides.
Nishant Gandhi -- Truist Securities -- Analyst
Great, thanks. So, the second one in terms of program starts, I mean, I know you have mentioned that, this quarter, you do not have any program starts and there is variability quarter to quarter. So, just wondering if this variability this quarter at least is it attributed in some level to the overall market condition or you think is just, you know, just one-off in the quarter that you did not have any program starts.
Andrew Booth -- Chief Financial Officer
Yeah. It's Andrew here. As you may recall, in Q4, we had a particularly strong quarter as well with nine program starts. It's just the way this metric is calculated, and it's quite clear in our statements and filings about how we calculate this.
There's very specific triggers that would constitute a program start. Just timing, I think, in the first quarter and the strong fourth quarter and then just resulted in very few or none in the -- in the first quarter. We do expect to have a strong number of programs starts in the duration of the year. So, that long-term metric that we've always pointed to as kind of a trailing 12-month metric I think is the way to -- to look at it.
And I think that's where you would look as we're going forward. It's not -- we don't think it's anything systemic that's out there, if that's what you're asking, in the -- in the health of the -- the -- the programs and partners that we have. We actually think it's very strong.
Nishant Gandhi -- Truist Securities -- Analyst
Thank you, very much.
Carl Hansen -- President and Chief Executive Officer
If I could just add maybe another -- yeah, if I could just add another comment on top of that. You know, so, you know, as Andrew said, you know, there's going to be fluctuation from quarter to quarter. In part, that's the nature of the type of business development that we do. So, we are not managing the business development and our business in general for -- you know, to hit quarterly numbers.
We are managing it to find and engage with the very best -- the very very best programs and the highest-value programs that we can find. In terms of, you know, the capacity, which I think is probably the thing that smooths out, and -- and looking at the work, you know, at any given time, we are working on, you know, perhaps 20 different partner-initiated programs. And over the past year, we have been doing more and more on those programs as we've built out capabilities to take programs further and further toward a value inflection point. So, the growth of activity has gone up substantially.
And layered on top of that, you know, over the last year, we've also announced initiation of more than 10 prepartnered programs. So, in terms of applying -- or in terms of executing the strategy, building capabilities, and using those capabilities to build a portfolio, we feel like there's been -- we're in great shape. And we're very, very pleased with the partners, partnerships that we have formed and the ones that we think are in the pipe coming up, so just wanted to add that -- that more color.
Nishant Gandhi -- Truist Securities -- Analyst
Great. Thank you very much.
Operator
The next question on the line comes from Gaurav Goparaju from Berenberg. Please go ahead. Your line is open.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Hey, guys. How's it going? You know, I just wanted to ask, how should we think about the average NPV of the split between the three program types, prepartnered, partner-initiated co-development, and you know, the standard partner-initiated discovery programs? Are you able to provide any color on how we should think about that? Or is it still early days, and we shouldn't think about it on a separate basis just yet?
Andrew Booth -- Chief Financial Officer
Yeah, I don't think you should look at it as a separate basis just yet, Gaurav. I think, you know, the partnership business, which you're quite familiar with, that we've been -- you know, large volume, small royalty stakes in those which we -- which we publish annually, how that's been progressing. And as Carl said, as we're doing more work generally, we're managing to command higher and higher economics, really focused on the royalty. It's easier to do the -- with such a number of them in that portfolio, you can do maybe that aggregate.
I think it's too early to try and put an NPV formula, or we don't have enough details about either the co-investment or the prepartnered programs. But maybe for a future time, that -- that might be appropriate.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Got it. And then, just a quick follow-up for me, just as a reminder, you might have touched on this earlier, I apologize, how many to date program starts if you had for prepartnered programs and then for co-development programs, respectively?
Andrew Booth -- Chief Financial Officer
Yeah, we have 17 co-development programs like under contract, of which I think we've initiated about six or seven. And on the prepartnered programs, we've initiated, I believe, it's 12 prepartnered programs. And that's a mixture of the TCE programs that Carl talked about, the difficult targets, and of course, our work in pandemic preparedness was actually the first prepartnered program.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Thanks, guys. Appreciate it.
Carl Hansen -- President and Chief Executive Officer
Gaurav.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Yeah.
Carl Hansen -- President and Chief Executive Officer
Carl here. I just wanted to add maybe another comment on top of Andrew's response there. So, one of the things I want to highlight is that, you know, whether it's partner-initiated or prepartnered programs, this is all part of building a diversified portfolio of stakes in future therapeutic programs. Now, there are some differences in the investment and in the risk-reward profile of these.
So, partner-initiated discovery programs, this is the highest-volume number. The return on investment for these is very high since we do the early work, and then, we hand it back to partners. And we have, you know, tremendous conviction in that as a long-term business. If you -- you know, if these are successful as they have been historically and you run the numbers in the long run, you end up with an outstanding, you know, P&L and without building a big balance sheet to fund all these.
And that's a business that we're going to stick by, and that's a key pillar of our strategy. Now, on top of those, we have opportunities where we can see the opportunity to have more conviction, and those are, you know, co-development programs. So, there'll be a smaller number, where any one of those, if they are successful, can materially change the business. And the prepartnered programs also have that profile with the added benefit that we control them, that we generate the data that we can then show to partners and to the market to demonstrate that we're making progress on the strategy.
And when partnered, we believe that those have the potential to generate very substantial upfront payments in cases where they're successful. Now, the nature of those is that we're working on difficult, well-validated, high-value targets. So, not every prepartnered program will result in an asset, but we do believe that we're making strong progress against that. And it's one of the parts of the business that we are most excited about.
But I also think it's a part of the business that people should give us value for when we've actually shown evidence that it's working. And so, at this point, you know, we wouldn't hazard to try to split what is the value between the different pillars. We think it's all part of one strategy, and it's about building a portfolio that generates value in the long term, and that's balancing risk-reward across the different programs that we run.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Awesome. Thanks for the colors, guys.
Andrew Booth -- Chief Financial Officer
Hey -- hey, Gaurav, just wanted to make one clarification point as well. So, the co-development programs are included in the program metrics that you see. But the prepartnered programs, in terms of starts, are not. And we've tried to be consistent with that.
But just to -- for added clarity, I wanted to point that out.
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Thanks for that, Andrew. Appreciate it.
Operator
The next question on the line comes from Puneet Souda of SVB Securities. Please go ahead. Your line is open.
Puneet Souda -- SVB Securities -- Analyst
Yeah. Hi, Carl, Andrew. Thanks for taking the question. So, first one, I mean, I appreciate the fluctuations in the program starts and overall macroeconomic climate.
But, you know, now with COVID somewhat behind, would it be possible to, you know, provide an annual -- maybe not a quarterly, as you pointed out, maybe an annual, you know, guide number from -- at least from the research fees perspective? And just wondering, you know, how should we think about, you know, in terms of the metrics that we ought to be tracking for the -- maybe at least on an annual basis.
Andrew Booth -- Chief Financial Officer
Hey, Puneet, thanks for the question. You know, we -- we are not looking to provide guidance on the research fees revenue, also because it's not where we believe the biggest value is that is reflected in kind of the metrics that we do present, which of course, are the -- the program starts and how we're building that portfolio. So, I think we don't have a plan to -- to provide that kind of guidance in the -- in the future for -- for revenue. Yeah.
And, Carl, I think you wanted to add something to that.
Carl Hansen -- President and Chief Executive Officer
Yeah, I was just going to say, you know, we definitely appreciate, you know, that people are building models are trying to get, you know, good -- good clarity on top-line revenue in the near term. From my perspective, I think our perspective, you know, we are executing a strategy to build capabilities and then build a stake in future therapeutic programs. Now -- and when market conditions get tough, there's a tendency for people to look on the short term. We think that optimizing or running the business for short-term revenue is the surest way to destroy value in the company.
And so, for that reason, you know, we are not providing guidance because we are not optimizing that in the business development. What we're optimizing is building strength in the capabilities and making sure that we're engaging those capabilities on the very best programs with the best partners to ultimately bring molecules through to the clinic and to have a significant piece of those. And so, that's the reason that we are, you know, reluctant to provide guidance on research revenue because that's not where we're steering the company.
Puneet Souda -- SVB Securities -- Analyst
OK. Fair. And then, on, you know, technology and the technology stack that you have developed, you know, Carl, maybe can you provide -- given the, you know, environment that we're in and the tight capital funding, are they -- you finding opportunities on the technology side to sort of, you know, grow the stack, grow the capability? Or do you see this as a time to largely invest into the partner program so you potentially have molecules down the line that -- that could provide upside? How do you think -- how are you sort of thinking about the sort of investments into the technology versus, you know, investments into the prepartnered programs?
Carl Hansen -- President and Chief Executive Officer
Sure. So, you know, when they're -- when there are difficult market conditions and capital is scarce, there's always an opportunity to look for M&A opportunities that make sense. And in the past, we have done that to bring on technologies that have helped to complete our capabilities on the front end. We're always looking at opportunities.
But right now, in terms of technology development, investment for capability building, the lion's share of that is going to be on completing the forward integration, so translational science, manufacturing, regulatory, and clinical capabilities that allow us to take programs from concept right through to IND. And that's where the -- the majority of the focus is today. And then, in terms of investments on prepartnered programs, these are programs that are being advanced in connection with high-value, long-range R&D. So, if you looked at how AbCellera is allocating capital today, it's the same that we were doing a year ago or two years ago.
And roughly, we have three -- probably two-thirds of our total investment on building technology and capabilities and about one-third on executing on the partnership business. And we expect that that will be the case for the next couple of years, at least, as we complete building the antibody discovery and development engine that we set out to build more than a decade ago now.
Puneet Souda -- SVB Securities -- Analyst
Got it. And then, just last one if I could clarify, was it ESMO you were expecting data later this year, or was that another conference that you mentioned?
Carl Hansen -- President and Chief Executive Officer
I don't think I mentioned the conference, but we are making rapid progress on the TCE work. And, you know, we will look at every opportunity to present updates when they're available at major conferences, and that would be an obvious one to target.
Puneet Souda -- SVB Securities -- Analyst
Got it. All right. OK. Thanks, guys.
Operator
The next question on the line comes from Malcolm Hoffman of BMO. Please go ahead. Your line is open.
Malcolm Hoffman -- BMO Capital Markets -- Analyst
Hi, guys. Malcolm on for Evan Seigerman. We wanted to start by asking if you could give a little bit of commentary regarding partners operationalizing collaborations with emergency. Have you observed changes to the economics of these new programs and updated terms for existing programs, or are they -- or are they -- there any other notable trends that you'd like to call out? And then, just secondarily, on the manufacturing side, how do you think about capex going forward? Is capacity focused more on kind of the developmental side and clinical or more toward scaling up toward the commercial end later on? Thanks.
Carl Hansen -- President and Chief Executive Officer
Yeah, so, it sounded like that was a two-part question. I'm happy to take the first part, but I didn't quite understand the nature of the question. Could you maybe restate that one, the first question? The first question was about business terms but didn't quite understand what you were asking.
Malcolm Hoffman -- BMO Capital Markets -- Analyst
Yeah, we were just looking for a little bit more commentary basically on the collaborations in general, the overview of kind of what the term structures have been like for some of the later-stage collaborations, and any trends that you're hearing from kind of your collaboration partners in general for those -- those new agreements going forward. Just thinking about the collaborations in general, really.
Carl Hansen -- President and Chief Executive Officer
Sure. So, you know, generally, the trend has been that as we add capabilities and do more work, our total value in -- in -- in a program has increased. And normally, we always look to have that value connected to the success of those molecules as they move to the clinic and, ultimately, to approval. So, that has been constant.
I'd say one of the more interesting developments over the last year in terms of the nature of our partnerships is that, now that we have built and scaled sort of the middle part of our engine, so to be able to do not just the early -- you know, early discovery and generating panels and hits and leads, but take those right through developability packages and translational work and come with the final clinical candidates that are ready for IND-enabling studies. That's a much deeper type of interaction. It's one that we think really differentiates us from many of the competitors that are out there, where there's -- there's been, in our view, a tendency for -- for groups to be providing sort of a shallow and thin offering that stops well short of what is a value inflection, particularly for the smaller companies. So, what that means is these are -- these are more deep interactions, and they're interactions where we will look to create value with partners in a way that's even more collaborative.
And I think that's a very positive thing for our business and one that we're excited about.
Andrew Booth -- Chief Financial Officer
Yeah. And, Malcolm, it's Andrew here. I'll take the second part of your -- I'll take the second part of your question, which is more around capex. And I think it fits in very nicely, of course, with the strategy that as Carl mentioned, where what we're building here is the capabilities to go from target to IND in the clinic in our antibody discovery engine.
And in doing so, the capital expenditure we're -- we're putting forward at the moment is really focused on those -- that vertical integration into CMC, GMP manufacturing capabilities in order to actually go from target to drug product that could start in a phase 1 clinical trial. As -- as I mentioned in the prepared remarks, we have the capital to continue those investments, as we have indicated in the past. And we have been, I think, quite capital-efficient in looking for nondilutive sources of capital, including that -- the help that we got from the Canadian Government Strategic Innovation Fund to co-fund 50% of that capital investment, building out that manufacturing facility. So, we have quite a detailed capex plan over the coming years as we complete the building of this engine and capability from target all the way to the clinic.
Malcolm Hoffman -- BMO Capital Markets -- Analyst
Thank you. Really appreciate it. Thank you very much, guys.
Operator
The final question on the line comes from Steven Mah of Cowen. Please go ahead. Your line is open.
Steven Mah -- Cowen and Company -- Analyst
All right, great. Thanks for taking the questions. A lot of ground already covered, so I just have one follow-up question on -- on a previous topic. So, you've talked quite a bit about the prepartnered discovery efforts, but could you provide some color on how you balance this internal R&D effort versus your partnered R&D efforts? Is there ample capacity at the company for -- for both? And especially as you think about adding new partners and new partnered programs, you know, as they start to mature, they potentially could require more R&D efforts.
So, how should we think about that from a capacity standpoint? And then, how should we -- and then, second part is how should we think about prepartnered program prioritization going forward given, you know, the higher cash burn? And you talked about it being offset by the potentially higher NPV of the wholly owned programs. But, you know, just -- just how should we just think about that going forward? I'm talking about more, like, long term, maybe not 2023. Thanks.
Carl Hansen -- President and Chief Executive Officer
It's a great question. So -- so, first, in terms of, you know, balancing partner initiated, of which there are two types there, discovery partnerships and co-development. versus prepartnered, you know, we're not trying to manage the business to a specific mix of those two. What we are doing is making sure that we're deploying our time and resources and capital on what we think are the most valuable programs to be working on.
And as I said before, we want to be diversified across indications, across modalities, and across risk-reward profiles. In terms of capacity, one of the things we've really seen over the last year is a major improvement in our throughput in the front end of the engine, which is what we would expect and hope to have seen given the investments that we've made over the last little while. So, the total activity that's ongoing in partner-initiated programs has gone up substantially. We've layered on top of that significant work on prepartnered programs that was already being resourced because it's part of long-range technology development efforts.
And we still have capacity to take on more programs at any time, so we are not capacity limited. Now, where that -- where that probably breaks down a bit is once programs move forward into the back end of the engine, so into translational science and certainly into manufacturing and beyond where we're still constructing those capabilities. And so, there's -- there's definitely a capacity limit there. And our job right now is to make sure that we are making the investments, doing the hiring, getting organized, getting economies of scale so that back capacity exists to take the programs that move into that part of the pipeline forward without having to take the foot off the gas.
The second part of the question was about, you know, capital allocation. You know, to be clear, prepartnered programs are not about us shifting strategy in any way. So, the intent is not to suddenly, you know, double down on a single thing and run it all the way through. We are -- we are taking these forward to the point where we can hand them off to partners and have created value by having solved a tough problem and anticipated partner needs.
And that -- that typically means that we're -- we're not going -- we don't expect to incur large costs, at least in the foreseeable future, connected with those. And we do believe that, as a business that, that has the potential to be cash generating in the near to medium term as we hand those over. So, we actually think that the cash flow profile of the prepartnered programs is a positive feature that complements well the discovery-initiated partnerships which, because they are mostly connected with royalties, have, you know, great cash flow but it's substantially -- on substantially longer timelines because it requires, ultimately, approval and delivery of therapies to patients.
Steven Mah -- Cowen and Company -- Analyst
OK, appreciate the color. Very helpful. Thank you.
Operator
We have no further questions, so I'll hand back to Carl Hansen for any closing remarks.
Carl Hansen -- President and Chief Executive Officer
Thank you, everyone, for joining the call. It's always a pleasure to provide an update, and we look forward to the next one.
Operator
[Operator signoff]
Duration: 0 minutes
Call participants:
Tryn Stimart -- Chief Legal Officer and Chief Compliance Officer
Carl Hansen -- President and Chief Executive Officer
Andrew Booth -- Chief Financial Officer
Andrea Tan -- Goldman Sachs -- Analyst
Antonia Borovina -- Bloom Burton -- Analyst
Steve Willey -- Stifel Financial Corp. -- Analyst
Nishant Gandhi -- Truist Securities -- Analyst
Gaurav Goparaju -- Berenberg Capital Markets -- Analysts
Puneet Souda -- SVB Securities -- Analyst
Malcolm Hoffman -- BMO Capital Markets -- Analyst
Steven Mah -- Cowen and Company -- Analyst