Cybin Inc. Common Stock Study update

Good morning, everyone, and thank you for joining us today. Whether you're a longstanding shareholder, a potential new investor, or a member of the analyst community, we appreciate your time and your interest in Helus Pharma. We are developing novel serotonergic agonists for the treatment of several important mental health conditions. Today, we will provide a comprehensive overview of both the science and the strategies that support our development programs and why we have confidence in our potential to positively impact the treatment of mental health. The agenda for today's program is designed to highlight the opportunity for HLP003 and HLP004, our clinical strategies, and why we believe our programs may offer meaningful differentiation from existing therapies. I'll begin with an overview of our pipeline. HLP003, which is deuterated psilocin, is our lead program and is currently in phase III development for the adjunctive treatment of major depressive disorder.

Our near-term catalyst is the upcoming phase III APPROACH top-line data readout, which remains on track with results expected later this quarter. The EMBRACE study, our second phase III efficacy study, is ongoing, and the EXTEND trial, our long-term extension study, is enrolling eligible patients from both APPROACH and EMBRACE. HLP004, which is deuterated DMT, is our phase III program in generalized anxiety disorder and provides a second clinical opportunity in another large area of significant unmet need. Today, we will share details of our next clinical study in the program, which we expect to initiate in the first quarter of 2027. Beyond these programs, our HLP005 library of preclinical compounds offers the potential for continued pipeline expansion. We expect to advance the lead candidate from this program in the second half of 2027.

All three programs are supported by a broad intellectual property portfolio, which is expected to provide patent protection into the early 2040s across 003 and 004. Our programs are targeting highly prevalent mental health conditions. Here is the scale of the unmet need. There are 22 million adults living with MDD in the U.S. alone, and more than 300 million people have depressive disorders worldwide. There are also about 20 million adults in the U.S. living with GAD, and more than 15 times that number are affected by anxiety disorders around the world. The scale of these conditions is substantial, but prevalence alone does not define our clinical and commercial strategies. We are focused on indications where the patient need is high, existing therapies have limitations, and the profile of our assets may offer clear differentiation.

Let me begin with why we chose to develop 003 for the adjunctive treatment of MDD, instead of choosing a development program in monotherapy or treatment-resistant depression. Treating depression with monotherapy is a crowded space with over 25 FDA-approved drugs, nearly all of them generic. While approximately a third of MDD patients respond to their first treatment, two-thirds have an inadequate response and do not reach remission. In order to treat patients having an inadequate response to therapy, clinicians can either switch to a different drug, which requires washing the patient off their existing therapy, a process that could take four to six weeks. Or the healthcare provider often chooses to add a therapy on top of the existing medication and continue the patient's journey towards recovery. The adjunctive therapy approach is a well-established treatment step for patients who have an inadequate response to first-line therapy.

However, there are only five currently approved adjunctive MDD treatment options. These are the atypical antipsychotics, and they have significant treatment limitations. We believe this creates a clear opportunity for a differentiated adjunctive therapy that can build on a patient's response to their existing therapy without requiring the clinician to restart the treatment process. In addition, the adjunctive approach has the potential to address the patient's condition before they fail to respond to multiple therapies and become treatment-resistant. Thus, we believe adjunctive treatment is the right indication to pursue, as it provides access to a significant portion of the MDD patient population earlier in the treatment journey in an area where there are limited approved treatment options.

Based on the non-clinical and clinical evidence we have generated to date, 003 has the potential to combine rapid and robust efficacy from a limited number of doses with a favorable safety and tolerability profile. As a result, we believe 003 could represent a very meaningful treatment option for patients. To better understand the opportunity ahead, it is important to first discuss the significant unmet treatment need impacting patients living with depression. I am very pleased to welcome Dr. Roger McIntyre, a leading expert in mood disorders, who will describe the unmet needs in depression, explain why new treatments are needed, and provide context on how 003 could fit into the MDD treatment landscape. Following Dr. McIntyre's remarks, Dr. Amir Inamdar, our Chief Medical Officer, will provide an overview of our 003 program.

Dr. McIntyre? Thanks, Mike, and good day, everybody.

Great to be with you. Roger McIntyre, Professor of Psychiatry, as well as the Professor of Pharmacology and Toxicology, University of Toronto. What I'd like to do today is just briefly cover two interrelated topics, the disease state of major depression and the treatment landscape. What should emanate, what should surround this concise presentation is that this is a prevalent, debilitating condition that has unmet needs that are a national priority for all of us to address. It really starts off with a description of major depressive disorder. This is a common condition. The estimated prevalence of this condition has been rising across the U.S., but also in other parts of the world.

When we step back and look at the longitudinal course of this condition, in other words, the lived experience, it is not the case that most people resolve the illness within a few weeks or a month or two. Most people, in fact, have multiple recurrences. For many, if not most people, it becomes very persistent. This degree of persistence of the condition contributes to the disability, the impairment in role function, human capital. We're not surprised when we read results in the U.S., around the world, that compared to all medical conditions, depression ranks number two. But within psychiatry, globally, major depressive disorder is the most disabling condition. So along with the suffering and the distress that depression entails, it is not only disabling and impairing role function, but it also is very costly to individuals, to society, and it's lethal.

In fact, we know that people with major depressive disorder lose, on average, 10 years of life because of this illness, in part because of the elevated rate of suicide. So the portrait that we sketch of depression today, empirically supported by a confluence of datasets, not just the U.S., but globally, provides for us a very clear, unambiguous picture that this is prevalent, it's severe, it's debilitating, and it is clearly very, very costly. Now, with respect to our therapeutics, we've already heard a state of the union, so to speak, of the therapeutics that are extant. They are currently available, ranging from monotherapies to adjunctive therapies. Despite the fact that we've had antidepressants available to us now for many decades, two out of three people who are diagnosed and treated for depression do not remit with the first-line antidepressant.

With respect to the inadequacy of our antidepressants, it's been amply documented that two out of three people are just not adequately benefiting. This is in part because the antidepressants themselves have relatively small to below medium effect sizes. The other part about this as well is that even amongst people who do remit, the third that are, if you will, the privileged ones that are benefiting, too often they have lingering problems in day-to-day quality of life and functioning. Now, one option could be to stop the antidepressant, that is the antidepressant that's been inadequate, bringing about remission, and switch to a different monotherapy. The other option is to adjunctively administer a treatment. There are several reasons why the switching option is less preferred than adding an additional agent. One reason just is simply the frequency of this occurrence.

Two out of 3 people who start an antidepressant do not adequately benefit. Secondly, what we do know is that when we actually ask prescribers, when we ask clinicians, we ask patients, "What is your preference?" The preference that they express, and this has been amply replicated, they would prefer to add something on in that context, in part because they don't want to go back to day zero, wash the medication out, and start all over again. Secondly, they want to perhaps take advantage of at least some type of therapeutic momentum, albeit inadequate, that may have been triggered by the first antidepressant. Other reasons, frankly, clinical practice guidelines, published in the United States, around the world, promote adjunctive administration in this context. As we've heard, the FDA has approved 5 agents in the adjunctive paradigm.