Bank of America's annual healthcare conference in very toasty Las Vegas. I'm very happy to be joined here on stage with Carl Hansen, with AbCellera. Thank you so much for joining.
Oh, it's great to be here. Thanks for having me.
Wonderful. Maybe for those who might be newer to this story, can you give us a brief overview of the company? You know, again, you've evolved from a successful discovery partner into a company now focused on advancing its own clinical assets. How did that evolution happen?
Sure. The company is now, you know, roughly 13 years old. It was started out of the University of British Columbia, where I was a professor at the time. From the early days, or in the first, let's say, decade of the company, we were really focused on a technology-forward strategy. We were building and integrating proprietary and best-in-class technologies to make a platform for the generation of novel and highly differentiated antibody therapeutics. The business model behind that drove that, was a partnership business model. We were essentially hired guns for the industry, and were, you know, the partner of choice when large pharma, highly enabled partners, ran into antibody discovery problems where their internal technologies were not up to the task.
That business really drove the company for the first 10 years. The model included early research fees as well as downstream stakes and programs. We were running this hired gun technology access for a stake in molecules that are moving forward, sort of a royalty aggregator. The company had a big breakout moment in 2020. We had been working with the Department of Defense, with DARPA, on a platform technology for a pandemic response. In March of 2020, we were able to deploy that. With Eli Lilly, we were successful in having two therapeutic antibodies that got Emergency Use Authorization that ultimately were used in about 2 million patients in the U.S., and we had a 25% royalty on that product.
Over 2021, 2022, 2023, that brought in about CAD 1 billion of non-dilutive capital into the company. You know, on the heels of that, we went public at the end of 2020, raised about CAD 650 million, and then subsequently were able to bring in another CAD 400 million in support from the Canadian Government. You know, the company had this breakout moment in 2020, and over the last few years, we have been completing that project of building a highly differentiated capability for generating antibodies, much of which was crafted and perfected in the context of solving some of the toughest problems in the industry.
In 2023, we made the decision that we now had the capital, we had the differentiated capabilities, we saw some very compelling opportunities, and it was time to take that capability and turn it inward to reform the company into a classic drug development company. Over the last 2.5 years, we've been basically heads down, reforming the company, moving those programs forward, and are now, you know, within sight of a very exciting first clinical readout and believe we have the ability to follow that up again and again over time. Have been on a bit of a push to reengage with the investment community because in a lot of ways, this is a new company profile and a new start to the next chapter of the company.
That's a great segue to the next question, which is, you know, when you think about the market's response, what do you think they're overlooking about how transferable some of these previous experiences are in terms of your success moving forward? I guess, what gives you an edge in antibody discovery?
Yeah. I'll start first with the edge. Like I said, like for ten years, we made our living solving challenging antibody discovery problems. In particular, I believe we now have best in class or best in world capabilities for some very important specific applications in therapeutic antibodies. GPCRs and ion channels has been a heavy focus. Our first program, which I'm sure we're going to talk about, ABCL635, is emblematic of that capability. We also have developed capabilities in multispecifics and more recently in ADCs. The platform build, you know, is highly differentiated. We can make molecules that are not me toos, but are getting into some new space where there's not much competition and is integrated all the way from discovery through now to manufacturing.
That's a very unusual setup for a company. But the market, I think rightly, doesn't want you to talk about a platform. They want to see what is the outcome of the platform. For the last two years, we've been setting that up and, you know, 635 is the first example. Next year we expect another two programs of a similar profile, ABCL688 and 386, to come forward. I believe over time, we're going to be judged on the differentiation of the platform as seen in the assets, as well as perception that we are taking that capital and that capability and directing it to bets that are going to have high return on investment.
You know, we're feeling really good about those first three programs and maybe another one coming behind it.
Got it. Well, let's pivot to 635. I mean, obviously, NK3R has been validated by small molecule approaches. I guess what gives you confidence an antibody approach could be potentially differentiating?
Sure. NK3R I think is a great example of how we think about selecting programs. As you mentioned, a lot of validation and now clinical validation with two small molecules. Coming into this program, I think our big risk was, will an antibody be able to engage and block NK3R in the part of the brain that is responsible for driving the hot flash process or instigating it, which is called the KNDy neurons in the infundibular nucleus.
We like this program a lot from the beginning because there's a well-established biomarker to test that target engagement in testosterone. Our view is that if we can get there and get strong blockade of NK3R, then we should be able to get efficacy that is at least comparable to what the small molecules have seen and perhaps even better. You know, our differentiation thesis is a antibody that has at least comparable efficacy, that has better convenience through a once monthly subcutaneous injection, and importantly, that does not have the safety liabilities that exist with the small molecules. In particular, both molecules have a warning for liver enzymes, the requirement for liver monitoring.
The first product that was launched, which is VEOZAH, post-launch has gotten a black box warning for liver injury. We believe that that is not because of an on-target effect, but rather metabolism of the small molecules, and an antibody obviously will not have that. We've got a real shot of having a cleaner safety profile, better convenience, and at least better efficacy and perhaps a scientific case that could lend itself to better efficacy.
Just assuming for a minute, just parity with efficacy here.
Yeah.
I mean, how do you expect prescribers to weigh both of those dynamics, the issues about safety and liver monitoring versus dosing convenience and enhanced efficacy?
Well, I think it's a big deal. You know, first of all, you know, there's a convenience advantage both for practitioners and for patients. In comparing a once daily oral to a once monthly subcutaneous injection, we have done some third-party market research, and that came back, you know, for equal efficacy and equal safety, that about 55% of women would prefer a once monthly injectable over a daily oral. What's interesting is if you, if you listen to the interviews, you see that there's a subset of patients that strongly prefer the injectable. It's like a no-brainer. There's also a subsection that do not want an injectable, they want oral.
Both are true, but on average, there's a preponderance of people that would prefer the injectable, and that preference goes up for anyone that has any experience with it. From a practitioner perspective, you know, both small molecule products require liver monitoring. If you don't want an injectable, then you don't get off the hook because you still need to go for blood draws and liver monitoring. And for VEOZAH, you know, that liver monitoring is quite intense. It's monthly in the beginning, and then a bit less frequent later on. A product that is more convenient for the physician to administer, a product that is more convenient to take for the patient, and one that doesn't have the same safety considerations, we think will be highly attractive.
In a market that gets developed by small molecules, being the only injectable, is a great place to be because we expect that there's Well, there's at least two small molecules now, and there may well be competition in that part of it as well moving forward.
Help us frame the third quarter phase II readout.
Yeah.
What levels of efficacy and then what do you need to see on safety has helped confirm that both are indeed differentiated?
Yeah. Great question. You know, I think it was like two days ago, we had our earnings call, and we released some of the interim data from the phase I study. You know, the important take-home points there were, so far we see a very clean safety profile, which is what we expected. In monitoring liver enzymes at all doses out 12 weeks, we see no indication of liver signal. Most importantly, we saw that target engagement in the infundibular nucleus, as measured by testosterone reduction, was superior at doses that are compatible with our TPP as compared to approved small molecules.
We have deeper testosterone suppression, and that testosterone suppression is sustained through the entire dosing period of a month versus transient suppression that happens only briefly and recovers to baseline in 24 hours for the small molecules. Already, you know, we have good indication that we're gonna see a good safety profile, that we'll have the dosing profile that we want. The last remaining question is, does the target engagement as measured by testosterone correlate with efficacy in the same way that has correlated with small molecules? If that is true, then we feel strongly that we're gonna have a drug, but we still need to get that readout. For us, success is, you know, equal efficacy or comparable efficacy with what they've seen in the small molecules.
You know, that's roughly 22% reduction relative to placebo, on the frequency measure. With that, we think we have something that could easily be a blockbuster product. You know, in the upside, we might see that we have better efficacy, then we'll open, you know, two bottles of champagne instead of one.
Well, we're rooting for you there. Let's just briefly turn to ABCL575 in the time we have left. Given all the growing interest in the OX40 ligand, you know, where do you believe ABCL575 can stand apart?
Yeah. you know, 575, first I'll say it's somewhat off-brand for AbCellera. It's a molecule that we got through a historic partnership with EQRx. The investment thesis for ABCL-575 was that we believed at the time that the OX40 ligand class could be a huge class, and that a molecule that was, you know, a terrific molecule, potent, and suitable for less frequent dosing would be in high demand as the leading molecules, amlitelimab and rocatinlimab from Sanofi and Amgen, made it towards their final studies. I'd say what has happened is, you know, the efficacy of those readouts, as well as the occurrence of Kaposi sarcoma has taken the shine off of the class in atopic dermatitis. Our strategy was always to move that forward and then look for a partner.
We're gonna read that molecule out at the end of the year. I think it's gonna be as billed. It's gonna look like a terrific molecule suitable for, you know, every six-month dosing. I think at this point, the prospects for partnering in atopic dermatitis are diminished. If we don't find a good opportunity, we'll hold onto it, but we don't have plans to invest further. My intuition is that, you know, the OX40 ligand class is gonna come back around, but it may come back around in a different indication or in combination, and we're gonna keep our head up and look for opportunities.
At this point, we are much more excited about ABCL635 and much more excited about the two molecules that we haven't yet disclosed, ABCL688 and 386, that are moving into the clinic and are much more on brand in terms of trying to get into not crowded spaces with compelling opportunities for unmet need by using an advantage in our technology.
Just real briefly, when you think about, five seventy-five.
Yeah
Is there anything about the readout that maybe doesn't necessarily help that program, but overall helps build that idea that your platform is distinguished?
I think that ABCL635 very much does that, so it's a potent antagonist of a GPCR target. ABCL688 will do that. ABCL386 will do that. OX40 ligand, in my view, is not a particularly difficult target. You don't need AbCellera to make a great antibody for it. I don't know if there's a lot of read-through on ABCL575 to the rest of the platform. I do think it You know, if you had a baseball card with stats, it may well be the best OX40 ligand antibody out there. Does that really matter is an open question.
We do think a lot about, you know, portfolio selection, the objective is by the end of, you know, by the end of 2027, if we get the right data readout, we could have 635 in late-stage studies, 688 disclosed and moving into patient populations, 386 there, maybe even another one. When you look at those programs, my belief is that you will say, "Yes, I understand there is real differentiation in that platform, management has done a great job of picking opportunities that make a lot of sense, and we're excited about all of those programs." But that's gonna take some time to play out.
Makes sense. All right, in the time we have left, what can you tell us about 688 and 386?
We've said very little. You know, for 688, we have said that it's from the GPCR and ion channel platform, and that has been a central strength of the company, and we've said that it's in the area of autoimmunity. For 386, we've only said it's in oncology. We're not saying much and I am sympathetic to investors that want to know more about the pipeline, but we have to weigh that against what has become an incredibly competitive world. We believe that it is in the best interest of the company and shareholders to hold our cards as close as we can until the very last moment. Now that we control manufacturing, we don't even need to file patents until we get close to the clinic.
We are, I think, routinely going to be, you know, trying to fly under the radar as long as possible so that we get a really substantial lead in moving programs that we have conviction in. Not much, unfortunately, but it's coming.
Fair enough. Looking forward to these next disclosures. Thank you so much, Carl, for joining.
All right. Thanks so much, Geoff .