Quince Therapeutics, Inc. (QNCX) Earnings Call Transcript & Summary

Good afternoon. I'm Michael Barrett, an analyst in Jefferies Healthcare Investment Banking. I'm delighted to introduce Chris Lowe, COO and CFO at Cortexyme to present at our virtual health care conference. We will leave a few minutes at the end of the presentation for audience Q&A. [Operator Instructions] And with that, I will hand it over. Thanks.

Thank you, Michael. Good morning, everyone. I am Chris Lowe, and I am the COO and CFO at Cortexyme. Like so many in our industry, this journey is deeply personal for me as well. We are committed to driving a new era in Alzheimer's and other degenerative diseases. Perhaps most importantly, we generate the evidence that drives that strategy. As you examine Cortexyme, I think you will appreciate the elegance of our evidence to date and the volume of evidence to be shared throughout this year. Our proprietary library of small molecules target a pathogen, which we believe is upstream of other targets within many areas of CNS. We absolutely believe this is the game changer patients have been waiting for. Our journey to stopping Alzheimer's in its tracks continues, and I am very excited today to be able to share our progress with you. Now, next slide. I will be making some forward-looking statements. So let's go ahead and get started. Cortexyme's therapeutic approach operates upstream of neurodegeneration with a mechanism of action that targets what we believe is the causative agent for Alzheimer's disease, specifically the infectious bacteria known as P. gingivalis. Our research takes an unprecedented approach in Alzheimer's disease with a novel class of drug focused on treating the cause of this devastating disease, not just the symptoms. Our lead asset, atuzaginstat, is a proprietary oral small molecule that is currently in a pivotal trial with not 1 but 2 large data readouts, both of which are expected in Q4 of this year. Top line data from the GAIN trial, a pivotal study in 643 patients with mild to moderate Alzheimer's disease, is expected in Q4 of this year. In addition, our REPAIR Phase II periodontitis study, a 233-subject substudy, is also expected to readout in Q4 of this year. Now the evidence base supporting our approach continues to expand with both independently replicated and confirmed research by laboratories around the world as well, of course, as our own ongoing experiments that continue to validate this breakthrough research. Our evidence base supports expansion into other indications as well. And we have a growing pipeline of small molecules, which are in development. Financially, we are extremely well funded to execute on all of these milestones with just over $170 million in cash as of the end of the first quarter. That gives us comfortable runway through 2023. Now examining the broader pipeline, in addition to the data readouts in 2021 utilizing COR388 or atuzaginstat, we are also expecting to introduce COR588 into the clinic later this year. COR588 is a once-daily oral dosing small molecule. In addition, our arginine gingipain inhibitor program continues to progress towards IND-enabling studies later this year as well. We believe our pipeline is diverse, growing and well founded upon causation evidence in all of these therapeutic areas. Now our growing evidence to date, including clinical and nonclinical experience, demonstrates that P. gingivalis -- that the P. gingivalis infection causes Alzheimer's pathology, including chronic low-grade inflammation and neurodegeneration. Most importantly, our evidence to date shows atuzaginstat, an orally administered brain-penetrating small molecule gingipain inhibitor successfully stops this infection. The growing foundation of evidence has now been replicated and published on by many other labs worldwide. We are very pleased that this expanding evidence base is continuing to grow the world's understanding of P. gingivalis. Our core research is indeed based upon the seminal discovery of P. gingivalis and its secreted toxic virulence factor proteases called gingipain. One of the first pieces of evidence generated by our research was a brain bank study conducted in collaboration with the University of Auckland. In this study, we proved the hypothesis of the presence of Pg in the brain. In the chart on the left, the gingipain load is demonstrated to be higher in Alzheimer's brains. In the chart on the right, we correlated one of the most common markers of neuropathology, tau, with gingipain load. The results, as you can see, are quite compelling. We have now found these gingipains to be in over 90% of the brains of Alzheimer's patients. This always grabs my attention no matter how many times I hear it. So let me just repeat that for a second. We have identified a bacterium in the brain that does not belong there. And we have a small molecule, which effectively targets this bacteria. We believe targeting P. gingivalis is the most direct and efficient manner to reduce the bacterial toxicity levels in the brain, stop neurodegeneration and the downstream host response of inflammation and A-beta production. Now among our research is our research in a wild-type mouse study, which shows that an oral P. gingivalis infection resulted in all the characteristic pathology of Alzheimer's, including A-beta plaques and inflammation. These results in a wild-type mouse study are unprecedented in Alzheimer's research. The data has been published and debated extensively over the years. And perhaps most importantly, we and others have now replicated similar results, demonstrating Pg causation. Indeed, this revolutionary research has become the pillar of our overall clinical development program. Our lead drug candidate, atuzaginstat, is a first-in-class gingipain inhibitor. And it's positioned to address both the Alzheimer's and periodontitis markets. These represent large market opportunities for Cortexyme. And frankly, our strategy is to shift the treatment paradigm in both of these markets. Atuzaginstat itself is a very elegant molecule. It's a potent small molecule, a very selective virulence factor inhibitor that specifically targets the lysine-gingipains. It's orally available and offers a 100% brain penetration. Atuzaginstat also selectively blocks the gingipain toxicity and effectively reduces the bacterial load with no evidence of resistance. And it has a very robust patent estate, which offers comp of matter protection through at least 2037. Now we learned a lot about atuzaginstat in our early clinical studies. First, atuzaginstat was very well tolerated in Alzheimer's patients. Second, we're also able to establish a wide dosing range, which covered the therapeutic exposures demonstrated in our previous animal work. We believe this wide dosing range will become particularly important in real-world settings where titration and dose escalation are utilized commonly by physicians. In our Ib -- in our Phase Ib study specifically, we also examined specific endpoints to inform the mechanism of action and target engagement. The chart on the left shows the rapid impact of atuzaginstat on RANTES, a validated marker of inflammation from infection. The chart on the right shows successful target engagement in the brain. These results clearly added another piece of foundational evidence to our overall development plan. Additionally, in our early clinical studies, we examined some exploratory cognitive measures. Across multiple measures of cognition, including a significant benefit on measures of speech and communication, we saw a clear trend reflecting clinically meaningful improvement in cognition. For us, it's this simple. If you block gingipains, we absolutely believe cognition has the potential to stabilize. This was another piece of critical evidence in our mission to be the game changer for millions of people suffering from Alzheimer's every day. Our early clinical experience certainly informed the design of our current GAIN trial. The GAIN trial is a very well-designed Phase III study with standard regulatory endpoints and broad dose ranging. The study is fully enrolled with 643 subjects. Based upon the baseline demographics and biomarker data, we believe we have the right patients at the right time for our mechanism. The GAIN trial also includes a 233-patient REPAIR substudy, which is examining periodontal disease within the GAIN patient population. The performance and dedication of patients, caregivers and clinicians absolutely inspires me and the entire team every day. Of course, I'm very proud to tell you that on behalf of our team, we will deliver top line data from both studies in Q4. This is indeed the dawn of a new era for Alzheimer's patients. Now the GAIN itself remains blinded, of course, we're now able to examine key baseline characteristics and biomarker data for all of our participants. Just yesterday, Our CMO, Dr. Mike Detke, presented the complete set of baseline demographic and biomarker data from our 643 participants at ASCP, the American Society of Clinical Psychopharmacology. One data set in particular from this presentation that I would highlight today is that we now know all patients in the GAIN trial have a P. gingivalis specific antibody at baseline, which is indicative of a systemic infection. Given that we did not prescreen patients for Pg, this is yet another strong indication that we've enrolled the right patients at the right time for this study. So the evidence supporting our potential therapeutic for periodontal disease is equally compelling, and I will speak to that program next. It's well established that P. gingivalis is indeed a keystone bacteria causing periodontal disease or periodontitis, where we know traditional antibiotics are not effective. The patients suffering from periodontitis are typically limited to very regular root cleaning and scaling, which tends to have a short-term and limited benefit and is costly often out of pocket. Our periodontal program is being examined in the REPAIR Phase II study, which, as I mentioned, includes 233 subjects. The REPAIR study itself includes very standard regulatory endpoints. And based upon our research with payers and prescribing physicians, we firmly believe this is a multibillion-dollar market opportunity with a significant unmet medical need in the U.S. alone. The REPAIR Phase II study is also on track to readout in Q4 of this year. Now the foundation of our research in periodontitis began with a naturally occurring periodontal disease dog model. This is the gold standard for nonclinical studies in this therapeutic area. The results demonstrated atuzaginstat has the ability to significantly improve pocket depth over the current standard of care. Pocket depth is the approvable endpoint, and we believe this evidence also provided important validation of other studies examining the mechanism and potential benefit of atuzaginstat. Examining the REPAIR substudy trial design, compromised -- or comprised of 233 patients, we are again establishing a very broad dosing range. And we get to study the subjects for a 48-week treatment period. We believe this is going to result in a very robust dataset later this year. And with clear regulatory endpoints to demonstrate efficacy in periodontal disease, we're absolutely excited about the impact of this -- of the design of the study and the impact of this upcoming data set. Now we also know quite a bit about the subjects in REPAIR. Specifically, when we examine the periodontitis study in participants in within the REPAIR study itself, we find that greater than 90% have moderate to severe periodontal disease at baseline. Okay? So let me repeat that again. When we examine these participants in the REPAIR study itself, greater than 90% have moderate to severe periodontal disease at baseline. While this is certainly supportive of the hypothesis for Alzheimer's, it's also significant foundational evidence in our approach to periodontal disease. Our understanding of how P. gingivalis impacts and traverses key parts of the human body is growing rapidly. We have the right patients at the right time to change how the world thinks about treating in these therapeutic areas. Now to fully -- as I mentioned earlier, to fully address the periodontal market opportunity, we're advancing COR588 into the clinic later this year. COR588 is a small molecule, also with high potency but with a novel structure, and we feel very confident it will be able to provide a once-a-day oral dosing. Having a once-a-day oral dosing option will be advantageous to us in the real-world patient settings. The growing evidence between P. gingivalis, Alzheimer's and periodontal disease has become extremely compelling in my book. Now our foundational research does not stop there. It's also created other opportunities as well, notably in Parkinson's, which I'll review next. Our research and the research of others indicate that P. gingivalis also can infiltrate motor areas of the brain resulting in Parkinson's disease. Like Alzheimer's, Parkinson's is characterized by spreading pathology and inflammation that can be triggered by Pg. Our partnership with the Parkinson Study Group remains focused on designing the proof of efficacy in this indication. And we absolutely are looking forward to the coming quarters and continuing to leverage their expertise as we move forward in this therapeutic area. Examining milestones in the near future for Cortexyme, there's little doubt that the collection of data to come will influence research in these areas forever. We will see top line data in Alzheimer's and periodontitis later this year. And we expect to have new data presented at a number of upcoming scientific meetings over the summer, including IADR and AAIC. As I stated at the beginning, this mission, this journey, it's deeply personal for me. It's a privilege to work with so many talented people who share a common goal. But energy and passion are only part of the equation. You have to have the conviction to listen to your evidence, and you have to have the courage to go where others do not. As the heroes of ancient Greece remind us, it is the cave you fear to enter which holds the treasure you seek. We are indeed the team that goes where others do not. We generate evidence, and we listen to it. I believe we're the game changer for the millions suffering daily. And in my mind, the evidence says the time is now to stop Alzheimer's in its tracks. Thank you. I'm not able to hear you, Michael.

Apologies for the delay. [Operator Instructions] The first question from the audience is on GAIN top line timing. Does Cortexyme expect to report top line data at CTAD in November? Or should investors expect to wait until December?

It's a great question. I think at this point, we're sticking to Q4 as our guidance. If we have the opportunity to tighten it up as we get closer, we certainly will, but for now, we can just simply say Q4. That's our high degree of confidence.

On the absence of any additional questions, Chris, we'd like to thank you very much for your time, and we'd like to conclude this session. Thank you.

Thank you, Michael.