Carl Hansen
Analyst · TD Securities. You may now proceed
Thanks, Tryn, and thank you everyone for joining us today. This first quarter, we continue to execute against our key priorities for 2025, which include: initiating Phase 1 clinical trials for ABCL635 and ABCL575; nominating one or more additional development candidates and moving these into CTA-enabling studies; completing platform investments; and starting to use our clinical manufacturing capabilities. Today, my prepared remarks are focused on providing additional details about ABCL635, including revealing its target and indication for the first time. ABCL635 is a potential first-in-class therapeutic antibody being developed for non-hormonal treatment of moderate-to-severe vasomotor symptoms, more commonly known as hot flashes, that are associated with menopause. ABCL635 targets neurokinin 3 receptor or NK3R, which is a GPCR involved in endocrine homeostasis and thermoregulation. Notably, ABCL635 is the first program from our GPCR and ion channels platform to advance into our pipeline. On our last earnings call, we discussed how we assess program investment decisions, and this slide summarizes our view of ABCL635 in each of the four dimensions of our investment framework. First, starting with the science, the NK3R pathway is well understood and has been clinically validated with small molecules, giving us high confidence in the biology. Accordingly, we believe the main scientific risk for ABCL635 is whether or not we can achieve sufficient target engagement. From a commercial perspective, VMS associated with menopause presents a large unmet medical need and a significant market opportunity. Approximately 30% of women experience moderate-to-severe VMS at some point in their lives, with more than half seeking treatment. ABCL635 has the potential to be the first antibody therapy in the NK3R class, a market estimated to reach over $2 billion in annual sales. With respect to differentiation, ABCL635 has the potential to be a first-in-class antibody treatment for VMS, with dosing every 4 weeks and an improved safety profile as compared to small molecules. And finally, this program has a well-established development path with potential for important early readouts on biomarkers and efficacy. VMS represents an underserved, underappreciated, and serious unmet medical need. They impact the well-being, the productivity, the career advancement, and the income of millions of women in North America alone. In the United States, there are approximately 40 million women of menopausal age. VMS are the most common symptoms of menopause, and as I noted earlier, about 30% of women will experience moderate-to-severe VMS in their lifetimes. The median duration of VMS is 7.5 years, approximately 12% of women will experience symptoms for more than 10 years, and in some cases, VMS can last for decades. This is why new treatments for VMS are an important addition to available therapies for women who suffer from this serious and long overlooked condition. Menopause Hormone Therapy, or MHT, is recognized as an effective treatment for VMS and is the current standard of care. While effective, MHT is not for everyone: approximately 12% of women are contraindicated for MHT; and 8% of women who begin MHT discontinue within 12 months. Additionally, in a recent global study, it was found that 57% of women who were eligible for MHT were against using it. Non-hormonal treatments for VMS are therefore an important option for women who either cannot or who choose not to use MHT. NK3R antagonists have recently been proven as effective non-hormonal options for the treatment of VMS. NK3R is a GPCR protein expressed by KNDy neurons that are located in the infundibular nucleus, also known as the arcuate nucleus, which is a region of the hypothalamus. KNDy neurons play a central role in regulating endocrine reproductive function and also impact thermal regulatory control via an interdependent neuronal pathway. Prior to menopause, KNDy neuronal activity is balanced by stimulatory NKB/NK3R signaling, and the inhibitory effect of estrogen. In menopause, when estrogen levels decrease due to the natural process of reproductive aging, this neuronal activity becomes unbalanced. As a result, NKB increasingly binds NK3R, causing KNDy neurons to over-activate and stimulate the thermal regulatory neurons in another region of the brain, called the preoptic nucleus, which leads to hot flashes. ABCL635 was designed to bind NK3R and to prevent the activation of KNDy neurons by NKB. Blocking NKB/NK3R signaling with small molecules has been clinically shown to reduce both the frequency and severity of VMS associated with menopause. Importantly, the infundibular nucleus responds to soluble factors in the blood and is therefore one of the few specialized areas of the brain that is not isolated behind the blood-brain barrier. Because of this, we believe that ABCL635 should be able to engage NK3R on KNDy neurons, and our preclinical studies support this hypothesis. Translating this result into humans and confirming that target engagement is sufficient to reduce VMS is the key scientific risk in this program. There are two small molecule NK3R antagonists that have recently been demonstrated clinically to be both safe and effective. Therefore, ABCL635 has the potential to enter the market at a time when the class has already been established and small molecules are approaching peak sales. Fezolinetant, a once daily oral treatment, was approved in May of 2023 and is the first available NK3R antagonist for the treatment of VMS. Elinzanetant, also a once daily oral treatment, successfully completed Phase 3 trials and is expected to be approved within the year. Unlike fezolinetant, elinzanetant is a non-selective antagonist that blocks both NK3R and a related receptor, NK1R. Because ABCL635 is an NK3R-specific antibody, we expect that it will avoid some side effects that have been observed with small molecules in the clinic. First, unlike small molecules that are metabolized in the liver, antibodies are generally not associated with liver toxicity. And second, because ABCL635 is specific to NK3R, we do not expect fatigue or somnolence that is believed to be related to antagonism of NK1R. In addition to having potential for improved safety profile, we also believe ABCL635 can achieve convenient dosing that would be preferred by a large fraction of women with VMS. To confirm this, we conducted a market research survey of 75 women who have VMS and found that, assuming equal efficacy and safety profiles, more than 50% said they would prefer the convenience of a once monthly injectable over a daily oral treatment. In addition, for the subset of women with experience using auto injectors, a large majority, approximately 70%, said they would select a once monthly injectable over a daily pill. In summary, the recent and upcoming approvals of novel non-hormonal treatments for VMS are an important and long overdue solution for millions of women. ABCL635 is being developed as a next generation NK3R antagonist with both an improved safety profile and a more convenient dosing regimen. If ultimately successful, we believe it can be a highly differentiated product that is launched into a large and established market. In terms of timing, our plans include completing the CTA process this quarter, starting our Phase 1 study in Q3 of 2025, and reporting key readouts of safety and early efficacy in mid-2026. As ABCL635 goes into clinical trials, we have high conviction in the biology, the differentiation thesis, and the unmet medical need. We expect the most important risk regarding target engagement will be addressed in Phase 1, making this an important near-term clinical readout. Turning to our second program, we have been advancing ABCL575 concurrently with ABCL635. It is also on track with a CTA filing in Q2, and we anticipate starting Phase 1 clinical trials in the third quarter. Later this week, our team will be in San Diego presenting preclinical data on ABCL575 at the Annual Meeting of the Society for Investigative Dermatology. You can download the poster presentation on our website when it becomes available tomorrow, May 9th. With our first two programs nearing the clinic, our transition from a platform company to a clinical-stage biotech is nearly complete. Behind ABCL635 and ABCL575, we are working on a portfolio of more than 20 internal and co-development programs from which we will continue to build our pipeline. As mentioned earlier, ABCL635 will be the first clinical program derived from our GPCR and ion channels platform. We view this as an important proof point that our technology can unlock these challenging and high value target classes, which represent approximately half of our preclinical programs. We expect to elect an additional development candidate from this platform in the near future and look forward to sharing updates with you as they become available. Similarly, we see our T-cell-engager platform as a source of internal programs and also as a basis for future partnering activities. Last month, we provided an update on our TCE platform, including in vivo data that was presented at AACR’s annual meeting. And finally, investments in building our clinical manufacturing are on track and are nearing completion. We expect to start using these capabilities later this year. And with that, I will hand over to Andrew to discuss our financials. Andrew?