Hello, everyone, and welcome to POINT Biopharma's Investor Day. My name is Daniel Pearlstein, Director of Strategy here at POINT. Thank you so much for taking the time to join us here today. Before we continue, please be aware that during today's presentation, we'll be making forward-looking statements which are based on our current expectations and beliefs. Please consult the risk factors discussed in our SEC filings for additional detail. Following our prepared remarks today, we will host a question and answer session. Additionally, today's presentation is being recorded, and a replay will be available on the investor section of our website shortly. I'm pleased to introduce you to some of our outstanding leadership team. Today's speakers include Dr. Joe McCann, Co-founder and Chief Executive Officer, Dr. Neil Fleshner, Co-founder, Chief Medical Officer, Justyna Kelly, Chief Operating Officer, Jessica Jensen, Executive Vice President, Clinical Development. And Dr. Robin Hallett, Senior Vice President of Discovery and Translational Sciences. This is our agenda for today. It's an agenda we're very excited about presenting to you today. Joe will kick us off with an introduction of why radioligand therapy now and why POINT? Part one will be done by Justyna, from neutron to patient, discussing supply chain and manufacturing, two large pillars of POINT's platform. Part two will be discussing next generation radioligands, where both Jessica and Robin will overview clinically validated radioligand therapy targets like PSMA, and also developing strategies for novel radioligand therapy targets like Fibroblast Activation Protein. Part three will commence with Neil discussing treatment site access and how we embrace radioligands. Joe will then provide some concluding remarks before we commence Q&A. Sit back and relax, and I'm pleased to introduce to you our CEO, Dr. Joe McCann. Thank you, Daniel. My name is Joe McCann. I'm the Chief Executive Officer and one of the co-founders of POINT Biopharma. POINT is a clinical stage precision oncology company focused on developing radioligands for the treatment of cancer. We have a pipeline of late stage and early stage assets that target large indications that use small molecules and peptides to deliver a radioactive isotope to a biomarker expressed within tumors, where the decay products from the radioisotope damage DNA and cause cell death. The mechanism of action has been validated by external beam radiotherapy, where you irradiate a tumor with an external beam of ionizing radiation that causes that DNA damage and that cell death. That approach lacks precision and cannot be used to treat micrometastatic disease or situations where there's extensive disease in patients. Radioligand therapies, when administered, systemically, take that concept of external beam radiotherapy, where you're irradiating that tumor tissue, but instead tie that radioactive atom to a ligand that seeks out those cancer biomarkers and delivers that radiation specifically and directly. Now, the use of targeting biomarkers with radioisotope has existed for over 50 years, with I-131 being the first real targeted RLT, where tumor tissue is the target, and this continues to be used today to treat thyroid cancer and is curative post-thyroid removal in many cases. We find it amazing there was such great success out of the gates. Very few radioligand therapies are available today. POINT believes the primary reason for this is that radioligands have very little in common with other drug classes, making it more difficult for traditional pharmaceutical companies to develop them. This difficulty spans from finding large sources of pharmaceutical-ready radioisotopes, to complicated radiochemistry and production, to just-in-time supply chains needed for drugs that have short shelf lives that measure in hours and days. POINT was founded to capitalize on this opportunity by building a biotech company focused on the unique requirements of radioligand development and commercialization. That solves the complexity of this supply chain from neutron to patient. There's a phrase achieved in our field: If you can see it, you can treat it. Using prostate cancer as an example, and with a patient shown here on the screen and PSMA as the target, you first determine the avidity. You can see in that image of the patient on the left, where the imaging agent has accumulated in the patient's disease, that are lit up in those black dots. You can see only faint amounts picked up in some organs and none in healthy tissue. That rapid clearance, that accumulation into the tumor tissue and that rapid clearance from healthy tissue is that profile that you want to see when you're looking at these drugs. On the right, you see the results of this treatment. This is the same patient. They've been imaged again, but this is after a few courses of a targeted radioligand. You can see that there is complete eradication of their disease. These results are what really motivated POINT to move into this space. It's incredibly exciting, the clinical outcomes that we're seeing both in the literature and now that we're seeing with commercial products coming to the market. As I mentioned, radioisotopes have been used to treat cancer and have known them to be safe and effective for over 50 years. I wanted to provide you some more details on why this space has lagged other modalities. Focusing on the column that shows past issues in the space, you know, these are real and have been really the driving force behind that limitation. This starts when we look at the isotope supply. Isotope supply has largely been controlled by government organizations that are not motivated to provide GMP supply of radioisotope, but are really motivated to look at academic endeavors and understand isotope production. That really limited the amount of isotope, that pharmaceutical radioisotope available to do clinical development. With that limited clinical development, there's really no understanding of how effective these drugs could be across many indications, and therefore no real appetite to understand and to build that manufacturing capacity to support that clinical development, to support commercialization. When there's a winner, like the drug Bexxar, it partially failed due to that limited capacity to make it, that limited understanding of that and use of that supply chain. There's limited clinical development going on, no access to commercial products, no one invested in the treatment sites to actually treat these patients. When something came forward that was exciting, it was only handled in very limited areas within very large hospital institutions. This cycle continued, and there's limited investment in the space, and therefore, really nothing has happened until the last five years. What's changed? Well, now we have private enterprises coming in, public and private partnerships, investing in radioisotope production, and they're making it at scale. At the scales that you can drive phase III trials, you can drive commercial products. We still need to continue to drive the manufacturing excellence in the space. This is an area where we're still seeing that there's some limitation, but there's now an understanding that with investment into manufacturing excellence, that will drive patient access, and that will drive commercial successes of these drugs. That's an area where POINT is really focused on, is that manufacturing piece to ensure that there's large volumes of the actual product available for patients. Isotopes like Lutetium-177, and Radium-223 are much easier to handle than I-131. The handling landscape has changed. This has increased the willingness of hospitals to invest in these products. Combined with the amazing clinical results that we're seeing, both academically and in commercial products, this has actually motivated hospitals and clinics to create greater access for these patients, 'cause they know that this is an option they want to offer to their patients that are coming through. Currently, there are key examples in prostate cancer. With potential blockbuster indication in prostate cancer, there's now investments going into the space to bring more companies forward, creating greater shots on goal in our industry that are gonna move more compounds in development. It's important to note here that this evolution is new, and it's really only been happening in the last three to five years. Even though things are evolving for the better, the space is complex, and the challenges are still there. The companies that can overcome these complexities will win in this space, and we built POINT to do this. Shown here are the four pillars that make up our platform, that will allow us to overcome these challenges and allow our pipeline to flourish and allow this field to grow. These pillars will be discussed more in this presentation, but we'll highlight them here. We have a well thought out radioisotope supply chain across lutetium and actinium, and we're also looking at bringing in other isotopes into our platform. The expertise to discover and develop new radioligands and advance them into clinical trials is inbuilt into POINT. The capacity and industry insights that we have as a team has driven efficient clinical programs from phase I to approval. Currently, right now, as I mentioned, we're at the tail end of completing a phase III trial. The commercial scale capacity that we have built in POINT will ensure there's ample supply to realize that true patient potential of these drugs. Shown here is our pipeline. I'll go through it in a high level. It's at a high level, but we have our PNT2002 program. It's a PSMA-targeted radioligand using Lutetium-177. Again, this program is in a phase III clinical trial for prostate cancer in the pre-chemo space, in castrate-resistant prostate cancer patients. The top-line data is expected to read out in the second half of 2023. We are developing it in partnership with Lantheus. The 2003 program is a DOTATATE-based compound using lutetium. We're also developing this in partnership with Lantheus. The programs shown below this, 2004, is a program focused on Fibroblast Activation Protein. Inhibitors Fibroblast Activation Protein is expressed in over 90% of epithelial tumors, virtually absent from healthy tissue, a perfect profile for radioligands. We licensed this from Tufts University. We're developing a whole range of compounds and looking at isotopes like Actinium-225 and Lutetium-177. Phase I' s results from the Lutetium-177 trial, called Frontier, will be shared in the first half of 2024. Our PNT2001 program is a next-generation PSMA-targeting radioligand that has an optimized linker that promotes greater internalization into the tumor, resulting in greater tumor accumulation. We're pairing that with Actinium-225 and planning to bring this into phase I trials in the first quarter of 2024. Below this is our discovery engine. It's focused on expanding our pipeline by identifying and assessing novel ligands, working with new radioisotopes, and investing in combinations across other drug classes in IO, in DNA damage response inhibitors, and in chemotherapies. Just a little bit of a highlight of, you know, the skill that is within POINT, and really that POINT has, that only really a handful of companies in our space have. Remember that POINT is just over three years old, yet we have years of experience of talented staff that we brought into the company. What you're seeing on the slide is the result of that, those decades of experience of our staff to drive a phase III clinical trial. That's very important to recognize, because this expertise, and remember, we conducted this phase III trial during a pandemic, completed it on time from our guidance, even from the formation of the company. In order to do that, you need that expertise, that's the expertise that really de-risks POINT as we move forward and look at running new or running clinical trials with new radioligands. We're incredibly excited to take this power that POINT has and apply it to new programs to drive the future of this space. What does the future look like? Where will POINT invest? Well, with our healthy balance sheet, we'll continue efforts internally to drive new products, and also look at licensing efforts to drive our pipeline as well. We'll add new isotopes to expand the toolbox of options for discovery and development scientists, and we'll become the partner of choice in the space to ensure this exciting technology reaches its full potential. I will now turn the presentation over to Justyna Kelly to speak about supply chain and manufacturing. Thanks, Joe. Hello, everyone, and thank you for joining. My name is Justyna Kell y. I'm the Chief Operating Officer at POINT, and I'm delighted to be here with you today to talk to you about supply chain and manufacturing. Highlighted here are just a few recent examples of manufacturing and supply chain disruptions that have impacted getting radiopharmaceuticals to patients. These disruptions have happened both at the level of production of the drug product itself and upstream during production delivery of the medical isotope. As you can see, these types of isotope shortages and supply chain disruptions are not new to the space. There's increasing interest in the therapeutic use of isotopes in medicine, and new players are emerging to solve these supply chain problems. Recognizing the importance of this, POINT has focused on supply chain and safeguarding from manufacturing disruptions since the inception of the company. I'm going to highlight a few of the strategies we've taken around supply chain today. The radiopharmaceutical supply chain from end to end is complex and unforgiving with respect to any delays. We call this a just-in-time process, as an isotope can't be produced and stockpiled on a shelf until it's needed for radiopharmaceutical production. The patient's administration date is the key date that drives all activities upstream from the POINT of irradiation of stable target material to produce the lutetium. From that POINT onwards, it is critical to coordinate all activities in order to ensure that the dose arrives on time for the patient. A key element to success is establishing redundancies at the most critical time POINTs to ensure dose arrival at the time of treatment. Since the inception of POINT, our focus has been on performing due diligence on the entire supply chain and partnering with key players to establish redundancies at every step of the supply chain. One of the key areas of focus for building redundancies to safeguard the supply chain from disruptions is at that critical POINT of isotope supply. We're able to obtain a supply of lutetium isotope from multiple external suppliers, and we established key partnerships in order to produce the lutetium isotope in-house. The redundancy of both external and internal isotope supply, combined with redundancy of having multiple external suppliers and partnerships for internal supply, helps ensure doses will arrive for patient treatment. Key partnerships include Kinectrics for the supply of stable target material, University of Missouri Research Reactor for targeted radiation, and the Belgian Nuclear Research Centre for lutetium separation and purification processes, as well as targeted radiation. We've also established agreements with multiple external isotope suppliers, including ITM and Isotopia. Isotope supply is determined by access and availability to the target material that is needed as the starting material to produce the radioisotope of interest and to the irradiation process the target material has to undergo. The target material is often a single isotope that needs to be isolated and enriched from a soup of other naturally occurring isotopes of the same element. Target material is obtained from specialized suppliers with access to key sources of raw material and technology to isolate and enrich that specific isotope that's needed. Similarly, targeted radiation or the ability to transform the stable isotope into the radioisotope, we need, requires very specialized equipment, a nuclear reactor, or a particle accelerator, or the technology and infrastructure to create isotope generators. There are experts at each of these steps in the medical isotope supply chain. POINT has established partnerships with each of these experts, both stable isotope suppliers and irradiation networks, to prepare for large-scale commercialization. We're going to take the same approach with any isotope we pursue. Our focus doesn't stop at lutetium or even actinium. We're looking at new ways to bring innovative isotopes to more patients over time. Reliable access to large quantities of new isotopes can trigger a new era of radioligand therapy innovation by ensuring we use the right isotope for the job. It can drive pipeline expansion by enabling us to reliably bring novel agents into clinical trials. Greater access to medical isotopes could shorten wait time for patients, reduce missed doses, and extend the reach of short-lived drugs. Now on to manufacturing, where we'll talk about the key infrastructure pieces of our platform. POINT has established two campuses. We have our commercial manufacturing campus located in Indianapolis, Indiana, which is the cornerstone of the company. We refer to it as CORE or the Center of Radioligand Excellence, we've recently established PIRI, or the POINT Institute for Radioligand Innovation, located in Toronto, Canada, as a hub for discovery and development. Together, these campuses allow us to develop, scale, and deliver the next generation of radioligand therapies. Our CORE campus in Indiana is one of, if not the largest in the world today. The campus includes two buildings, as you can see here. CORE one or building one, is where we currently operate, and we have our over 70 highly skilled employees here today, including manufacturing, quality control, quality assurance teams, as well as engineering and technical operations and supply chain. Our team continues to expand here as we prepare for commercialization. CORE one has provided over 80,000 sq ft, where we continue to build out operations in a phased approach. CORE two provides an additional 100,000 sq ft for future production expansion. As you all know very well, the key to success in the radiopharmaceutical industry is to deliver product with a very short shelf life to patients as quickly as possible. Our location in Indiana, known as the crossroads of America, enables us to reach about 50% of the U.S. population within an eight-hour driving radius from the site. We can reach most of the remaining U.S. population within about 12 hours through a combination of flights and local couriers. Beyond the U.S., we're able to reach other major markets around the world, including Canada and the EU, within 72 hours. Our campus is close to the Indianapolis Airport, which includes the FedEx shipping center and HazMat hub, as well as other major airports, including Chicago O'Hare. We purchased the first building in early 2020, gutted the inside, and we're scaling build-out in a modular fashion to prepare for the anticipated commercial launches of both PNT2002 and PNT2003. Working with Inizio, we have been planning for commercial success based on the modality of radiopharmaceuticals and not any one particular program. The design of the facility is focused on the unique needs of radiopharmaceuticals, driven by the safe handling of radioactive materials. This includes focus and special consideration to engineering controls, radiation shielding throughout the building, and storage and handling of radioactive waste. The design is also forward-looking, with a deliberate design focused on minimizing downtime to ongoing production and enabling build-out of new production lines without impacting existing GMP operations. We also have a lot of planned space for development activities and scaling of late-stage and commercial processes. The building within a building concept that you see here allows us to scale and expand while maintaining our current operations. Clear wall panels are modular and can be removed or reconfigured and replaced quickly and efficiently. Separate and dedicated air handling prevents disruption to adjacent production lines, which allows us to install equipment and build out lines without interrupting production in other areas of the facility. Our goal is to ensure capacity ahead of commercial launch and to scale capacity ahead of demand to ensure patients have uninterrupted access to radioligand therapies. We're focusing on medium and high volume production lines that are flexible and nimble and can produce beyond expected demand, as well as redundant production lines to ensure continuous supply of all our products. The facility is licensed with the Nuclear Regulatory Commission for alpha, beta, gamma, and positron emission radioisotopes at levels that enable us to scale to commercial levels of radiopharmaceutical production today. Many facilities don't plan adequate support space for scaling operations. As a result, lab space, radioactive material, waste storage space, and GMP material storage space is planned as an afterthought with insufficient space allocated. We have dedicated development and engineering space, as well as six core labs for QC and microbiology testing, which ensures we're able to scale capacity. You see here a few of the labs at the POINT facility. We also have dedicated radioactive material, waste storage, GMP material storage, and radiopharmaceutical packaging areas at a scale that can support commercial operations. Our facility was not only designed for the production of radioligands, but also for the in-house last mile production of the lutetium isotope itself. As I alluded to earlier, part of the just-in-time manufacturing, lutetium is ordered and produced just days ahead of radiopharmaceutical production, and a shipment of isotope, which is ordered specifically for each batch of radiopharmaceutical products we produce, has to arrive on time in order for patients to receive their doses. Production and delivery of isotope is therefore a critical POINT in the radiopharmaceutical manufacturing process. No isotope arrives, no radioligand is produced. By producing our own no-carrier-added lutetium in-house, we control this critical aspect of radiopharmaceutical production. We're able to ensure that stable isotope target material is available. We can irradiate it at local reactors to ensure irradiated targets don't get delayed on international flights, and we minimize the decay and loss of lutetium through a shorter delivery time from reactor to our facility. We're also able to execute that key separation process in-house to produce the lutetium isotope in its final form. Having the ability to produce lutetium in-house decreases the likelihood of production delays and allows us to control the supply chain at one of the most critical time POINTs. Shown here is one of four of our isotope production suites, as well as a large radioactive material storage facility for liquid waste that's produced as part of the isotope production process. We've been growing very quickly over the past two years, and we need more space for our talented team. We just recently leased this building located right next door. This space, the second building shown here, provides an additional 100,000 sq ft for future expansion, including additional office space and parking. We plan on taking a very similar approach in this, in the build-out of this production space and in the second building, with that building within the building design that will allow us to scale operations as needed. As I touched on earlier, we also recently opened the POINT Institute for Radioligand Innovation, or PIRI, which will be a hub for discovery and translational research at POINT in the future. This state-of-the-art facility is equipped with infrastructure and instruments required for a wide range of activities, including discovery, radiochemistry, development of GMP processes, and routine clinical production. Ahead of large-scale operations and commercialization, PIRI is instrumental to the research and development needed to generate the data that will enable us to bring novel programs from discovery into the clinic and drive decisions within our pipeline in a capital-efficient way. With that, I will pass the spotlight on to Jessica Jensen and Robin Hallett to discuss next-generation radioligand therapies. Thank you, everyone. Thank you, Justyna. As a leader of clinical development at POINT, it's very exciting to have such a confident and focused team at our commercial manufacturing campus and now at PIRI. It is with this infrastructure, especially PIRI, that I envision the opportunity to accelerate innovation and translate the development of next-generation candidates. As we all know, PSMA has now demonstrated evidence of clinical utility as both a diagnostic and therapeutic target. Despite the recent advances and flurry of approvals for PSMA PET and lutetium PSMA, this innovation has evolved over more than 20 years, demonstrating significant technological advances since the first approved PSMA-directed SPECT diagnostic process in 1998. It is with these recent new approvals and continued validation of the target that serves as a foundation for innovation and next-generation therapies, including isotopes with greater tumor-killing properties and ultimately having patients avoid succumbing to their fatal state of disease. In the case of prostate cancer, metastatic castration-resistant disease, this is where we believe we can transform the disease landscape. It is with Actinium-225 PSMA-targeted ligand therapy that we hope to make a difference. As you know, we have a very talented and experienced uro- oncology team at POINT, from inception of the company, we've been thinking about how to bring radioligand therapy to more patients and earlier in the patient's disease state, with an ultimate goal to reduce mortality and avoidance of a man's fatal state of their disease, castration resistance. By moving earlier in the disease process, in biochemical recurrence or oligorecurrent disease, we may have the opportunity to eradicate micrometastatic disease at an earlier disease state, inhibiting future progression and metastases, or hitting the disease with an alpha isotope post-progression. That is exactly how we've approached development of our novel next-generation PSMA-directed compound, actinium-labeled PNT2001. PNT2001 was the first program we ever in-licensed and have been working on product development in both post-lutetium patients and patients much earlier in their journey with prostate cancer. We will discuss more about this phase I study shortly. I'll now hand this to Robin Hallett. Thanks, Jessica. Hi, everyone. My name is Robin Hallett, and I'm the Senior Vice President of Discovery and Translation at POINT. Our PNT2001 program was actually the first program brought into POINT, as we've always had the vision to develop the next generation of targeted radioligand therapies. PNT2001 was invented at the Technical University of Munich by Hans-Jürgen Wester, who is also the inventor of the PSMA I&T ligand. This is the ligand of POINT's PNT2002 program. We worked with the Wester Group to test derivatives of PSMA I&T with markedly improved tumor cell internalization. Our lead for this program, PSMA- 62, is hype-rinternalizing relative to first-generation PSMA ligands and also shows reduced normal tissue uptake relative to PSMA I&T, making it ideal for pairing with the alpha emitter actinium-225. We expect our first patient in for this program to occur in Q1 2024. We've compared the efficacy of actinium-labeled PSMA- 62 with actinium-labeled PSMA I&T in an aggressive model of metastatic prostate cancer. This is the data we presented at last fall's EANM meeting, which showed very convincingly that actinium-labeled PSMA- 62 significantly outperformed actinium-labeled PSMA I&T. The panel on the left shows tumor burden measured over time for control, actinium-labeled PSMA I&T, and actinium-labeled PSMA- 62 treated mice. Mice treated with actinium-labeled PSMA- 62 have lower tumor burden than either control or actinium-labeled PSMA I&T-treated mice. This also translated to increased survival for PSMA- 62 treated mice relative to both control and PSMA I&T treated mice, as shown in the right-hand panel. PSMA I&T treated mice had also come to disease within 60 days post-injection, whereas all PSMA- 62 treated mice were still alive at this time. Back to you, Jessica. Thanks again, Robin, we're proud to unveil here for the first time our trial design for this clinical candidate, our first actinium-based clinical trial, which we call ACCEL. The design speaks to our expertise in this space by structuring this study to explore, looking at both later-stage metastatic castration-resistant prostate cancer patients and earlier-stage biochemically recurrent or PSMA-positive oligo-recurrent patients in parallel. ACCEL is a first-in-human, phase I, phase II multi-center study that will commence with a phase I dose escalation, which we present here. We anticipate our first patient in this trial in Q1 2024. You see presented here our dose escalation paradigm, leveraging BSA-based dosing. Phase I dose escalation enrollment will initiate for patients with metastatic castration-resistant prostate cancer. We'll enroll approximately 30 patients with a maximum targeted dose of 6 MBq per meter squared, or approximately 14 MBq. Please note that there are dosing differences between a lutetium dose based in gigabecquerels and an actinium dose in megabecquerels, and we will evaluate dose finding of both populations in parallel. While this phase I study is focused on identifying a recommended phase II dose, we will be closely monitoring early efficacy signals to move quickly based on a positive benefit-risk profile for an accelerated clinical development plan. Based on our expertise in PSMA-directed radioligand therapy, as well as our established actinium supply relationships, we are excited to advance this development plan. I will now turn it back to Robin Hallett. Thanks, Jessica. We are now going to switch gears and talk about additional work we are doing to create the next generation of targeted radioligand therapies. The mechanism of action of targeted radioligand therapy is radiation-induced cell damage or cell killing. The essential property that determines if a targeted radioligand is successful is where does the radioligand go and how long does it stay there for. This is what influences how much radiation is deposited into tumor and normal tissues. An ideal targeted radioligand can be used with both imaging and therapeutic isotopes to enable both the selection of patients with a high probability of responding and also the delivery of large radiation doses specifically to tumors. In order to do this, the targeted radioligand must specifically target and retain in tumor tissues while rapidly washing out of normal tissues. POINT is working on a number of new early-stage programs. We wanted to provide some insight into our philosophy on this process. For all new program concepts, we ask ourselves the question: Where will this targeted radioligand go, and how long will it stay there? We pick targets that have what we believe are the right expression profile to enable delivery of radiation, specifically in tumors. We also design properties into the therapeutic to match the planned therapeutic isotope and is also customized to the patient population we intend to treat. For example, a ligand with tumor-specific distribution but shorter residence time will pair more effectively with a short-lived isotope, where a patient population with predominantly micrometastatic disease will derive more benefit from isotopes that deposit energy in a short range. We are also leveraging imaging and dosimetry data to accelerate the development of new targeted radioligand therapies to ensure we make smarter and data-driven decisions on which programs to invest aggressively in. Building on the theme of the essential property of our therapeutics being where do they go and how long do they stay there for, we can integrate early human imaging studies, potentially with multiple program leads in parallel, to assess which lead has the most promising biodistribution profile and is the best candidate for further clinical development. I'm going to talk about one of our early-stage programs. Fibroblast Activation Protein, or FAP, is an extremely compelling target for the imaging and therapy of cancer. FAP is normally expressed during embryonic development and at very low levels in normal, healthy adult tissues. FAP is expressed at very high levels in the vast majority of epithelial tumors, and FAP imaging studies have shown the presence of FAP in virtually all major tumor types. These imaging studies provide proof of concept for the delivery of tumor-specific radiation in cancer patients. We believe theranostic approaches will allow both precision imaging and therapy of FAP-positive tumors. Successful theranostic FAP-targeted agents will require high affinity and selectivity for FAP and rapid clearance from normal tissue with sufficient tumor residence time to deliver tumor-killing radiation. The goal of therapies we develop are always to maximize the delivery of tumor-specific radiation. FAP radioligands generally show much less normal tissue retention relative to other radioligands, such as those that target PSMA. For example, FAP-based PET imaging does not show signal in the salivary and lacrimal glands and much less signal in kidneys and liver relative to PSMA-based ligands. We hypothesize that targeting FAP with therapeutic radiation will have a very large therapeutic window by virtue of not having significant distribution into normal tissues. We've found that our therapeutic FAP-targeted radioligand, lutetium labeled PNT6555, is extremely efficacious in preclinical animal models. It shows dose-dependent antitumor effects, which you can see in the panel on the left, as well as significant survival extension across multiple dose levels, which you can see in the panel on the right. Notably, we've also seen similar results with our actinium-l abeled PNT6555 molecule. FAP as a target is a new frontier in the field of targeted radioligand therapeutics, and we are compelled by the opportunity it presents to provide benefit to patients with cancer. There are still many areas that we are exploring in order to understand how to optimally deliver radiation to tumors by targeting FAP. These include deepening our understanding of FAP expression across and within tumor types, as well as changes in FAP expression over time or in response to therapy, defining entry criteria based on FAP imaging, and assessing advantages of FAP imaging compared to more conventional imaging modalities. Finally, defining optimal dosing regimens or strategies that take advantage of the fast clearance and reduced normal tissue retention of FAP-targeted radioligands, and isotope selection to maximize the radiation absorbed dose by tumors. Back to you, Jessica. Thanks again, Robin. We began the phase I Frontier trial in July 2022 and have enrolled seven patients to date across colorectal, pancreatic, and soft tissue sarcoma. The study is now recruiting patients across all the disease states you see presented on this slide. Those we believe to be highly radiosensitive, have excellent opportunities as a combination agent, and those with proven high FAP expression. Similar to what we discussed with the ACCEL trial earlier, Frontier is also evaluating a recommended phase II dose in this phase I study. I will review various endpoints presented on the next slide. We are currently at our highest dose level, screening patients for 12 GBq, with a total dose population of approximately 30 patients. To date, this Frontier trial has enabled our team to learn about the molecular target of Fibroblast Activation Protein. These learnings, including the biodistribution profile and benign safety profile with no DLTs to date, will enable us to enhance our development plans, including patient selection criteria and strategic endpoints for further development, with an ultimate goal to optimize for efficacy. In this trial, you see presented here very robust radioligand therapy, exploratory and secondary objectives. With our current cohort under evaluation at 12 GBq, we expect to present data on these objectives in the first half of next year. In totality, our experience advancing our phase III trial with the FDA has enabled strategic development considerations for this phase I first-in-human trial with a novel target. I'll now turn it over to Dr. Neil Fleshner. Thank you, Jessica. My name is Dr. Neil Fleshner, Chief Medical Officer and Co-founder at POINT, today I'd like to talk to you about radioligand therapy treatment site access, and frankly, I think what many people don't understand about the ubiquitous aspect of nuclear medicine. As a practicing physician, I can tell you that nuclear medicine is infused in almost every day of my clinical practice. Radiopharmaceuticals and radioligands are complex molecules, but they are used really around the world. In fact, it's been estimated that in the developed world, one in 50 patients require a nuclear medicine encounter each year. In addition, over 10,000 hospitals worldwide use radioisotopes in the delivery of clinical care and are infused with the infrastructure to do that. This translates in the U.S. to approximately 20 million nuclear medicine procedures being done every year. To date, most of them are in the diagnosis phase, certainly, the therapeutic one is starting to catch up. Not surprisingly, in order to deliver these 20 million or so scans every year, there is a large infrastructure for diagnostic nuclear imaging. The radioligand piece, however, has great potential to grow. If you look currently around the footprint of nuclear medicine in the United States, there are over 13,000 SPECT scanners, 2,500 PET scanners, and many of these are now being swapped out for the more updated PET/ CT platforms. In total, this represents 18 million SPECT scans, 2 million PET scans, and this will be growing. Of course, what's interesting about this is these institutions that perform all of these scans have the appropriate radiation safety and appropriate infrastructure to really minimize the hurdles of transitioning from a diagnostic platform. T o a therapeutic platform in a minor way, because they know how to handle isotopes, and they know how to look after patients in the nuclear medicine realm. An interesting fact as well about imaging in nuclear medicine is that because the same ligand is used for the imaging and the therapeutics, we believe that the radioligand therapy has effectively a symbiotic relationship with the diagnostic realms of the treatment. For example, you could imagine patients having multiple scans because of the possibility of radioligand therapy. For example, a patient with high risk cancer features may be staged with a PET scan. He or she may be treated, and if the cancer returns, a second PET scan done to determine sites of recurrence and whether recurrence has happened at all. These scans could then be used for selecting patients for radioligand therapy, because, of course, if the ligand lights up on imaging, then that patient's generally a good candidate for radioligand therapy. You could also imagine newer realms of guided therapeutics, such as guided surgery and guided radiotherapy, that also involve the same tracers. We really foresee a feedback loop between radioligand therapy and radioligand-based imaging as this whole field of theranostics continues to expand. There is already a well-established infrastructure to deliver these therapeutic isotopes. It's extremely important to recognize that the novel therapeutic isotopes do not require lead line rooms. They're simple, outpatient, intravenous infusions, and this will make them very user-friendly for both centers and patients alike, and allow a growing network of radio pharmacies and treatment centers. This map that you see below simply has pins on radiopharmacies and treatment sites for radioligand treatments across America, this continues to grow, and this continues to expand, largely in treating the large burden required for prostate cancer and neuroendocrine cancers. These pharmacies, again, have large infrastructures, and they will be able to expand their capacities, as well as new centers coming into the field, in order to enable our patients to have access to the best treatments necessary and proximate. I think one of the also important lessons learned in this industry is because the agents themselves are radioactive, best practice guidelines in nuclear medicine departments really recommend establishing redundancy and multi-sourcing as ways to minimize impediments or shortages of these drugs. On the left, you can see a screen capture from the government of Canada around lessons learned from the shutdown of a local nuclear reactor. You can see in the red bullet that hospitals and radio pharmacies should secure sources from more than one supplier. The same message on the right from the Nuclear Energy Agency and the OECD, suggesting that multi-sourcing is an important part of securing supply for our patients. There's a lot of lessons learned from the technetium and molybdenum shortages some years ago. We feel that the same practices will likely apply to therapeutic isotopes as well. Lastly, I think another factor that we at POINT think about all the time as we try to improve our patients' access to these important medications, is thinking not only about the production of the drugs, but also how centers dispose of the waste that they generate. We think that this is important because we feel it'll improve patient access and reduce burden on outpatient centers and hospitals. Remember, because these drugs are radioactive, they're governed by both the FDA and the NRC, and that the supply chain manufacturing aspects, as well as the waste disposal, all go into the NDA applications. We're very cognizant of this at POINT, and we're very adamant that aspects of drug development, things such as long-lived impurities, will not be in drugs that we produce, in order to improve patient access and improve public health. Thanks for your time today, and I'm going to turn it over to Joe McCann, our CEO. Thank you, Neil, and thanks to everyone in our audience for your attention today. Before we move on to Q&A, I want to highlight a few things for you. This is an exciting time for POINT. We are a highly differentiated platform, poised to lead in this exciting modality, for which the market potential is growing significantly. Our early investments in manufacturing and supply chain positions us as one of the very few vertically integrated, large-scale, commercial-ready therapeutic radioligand companies in the world. We have a demonstrated success in both the development of novel radioligands and clinical development of late-stage programs. We are using our unique capabilities and internal expertise to develop potential best-in-class agents in large indications with high unmet need. Here's a graphic that kind of helps you show the execution from our young organization. We've leveraged those decades of experience in RLT to move quickly with our phase III program that completed recruitment in December 2022. Built out our Indianapolis facility to supply product that started in January of 2022, and the start of our FAPI program in the summer of 2022. We'll continue to execute in this fashion across our platform for years to come. Now, looking towards the future, and starting with the top line data from the SPLASH trial, we expect that in the second half of this year. Other data readouts include our phase I data from our FAPI program, which we expect to share in the first half of 2024. Clinical data update for our actinium PSMA program by the end of 2024. We also expect in this time to disclose two new development candidates, with the goal of having five new programs in humans by the end of 2028. All of this is fueled by a strong balance sheet that will take us into 2026, that could be extended even further if PNT2002 is approved, which would trigger our $250 million regulatory milestone payment from Lantheus, as well as royalties and manufacturing revenues. We have some exciting inflection POINTs in the next 18 months and a proven team, capabilities, and technologies in place to execute on our strategy. Thank you for your time today. I'll now turn it over to Daniel to host our Q&A. Thank you everyone, for taking the time to participate today. We really appreciate it. We're just gonna have our panelists roll in here and allow the Q&A portion of the chat to populate a little bit. I saw a few hands come in already, so we'll start with Charles Zhu from Guggenheim. Your line should be open here shortly, so take it away, Charles. Good afternoon, and thanks for hosting this event and for taking our questions. First one from us regarding FAP and PNT2004. Can you provide more color around how you might potentially enhance your patient selection criteria relative to the current inclusion criteria in the dose escalation? Should we think about this potentially as a narrowing of a priority histologies for expansion cohorts, or maybe something like an SUV cutoff for tumor, by tumor, by radioactive uptake, or something else? Thank you. Thank you, Charles, and, thank you for attending. I'll actually turn that over to Jessica, to add some more color there. Hi, Charles. Thank you for your question. When we identify optimal criteria for patient selection, typically what we do is look at the reference organs to identify the proper background organ to use, and we try to not create a too quantitative of a measure for patient selection, but more of a qualitative measure that can be extrapolated to a commercial read paradigm in as easy a way as possible. In our experience working with the FDA on this, they really like this to be generalizable as much as possible, but refining what you learn from very early reading days based off of your normal organ background, that is used, identifying potentially a ratio to that normal organ background, and then optimizing it to that right balance of not excluding too many patients, but ensuring the right patients are included. As of right now, we're using liver as our background. That could evolve to a blood pool background. We evaluate all of this as we're looking at the data and looking at signs of patient inclusion, patients that were eligible, not eligible. It's really looking at the totality of the data, looking at the reader's interpretation, and understanding what can be extrapolated to a commercial paradigm. Great. Thanks for your question. Yes, that does, and thanks for that useful color. Maybe one more from me before I hop back in the queue. I probably missed this, but with respect to the development of PNT2001 in early stage prostate cancer, can you clarify if you're planning this as a single agent or in combination with androgen deprivation therapy? Perhaps also longer term, with respect to a hypothetical control arm in a registrational setting, how are you evaluating the potential need to randomize against ADT alone or potentially ADT combined with other agents, such as novel hormonal therapy or docetaxel? Thank you. Yeah, great. I'll let Jessica take that one as well. Thanks. Thanks, Charles and Joe. In our, in our phase one, we are studying two populations, as a reminder, mCRPC and BCR. In the BCR setting, our ultimate goal is to try to stave the use of hormones, and we are evaluating this prior to ADT initiation. In mCRPC setting, once a patient does start ADT, you typically never take them off ADT. ADT will be used in that, in concomitantly with that, within that population. As we're evaluating the full development plan and pathways for next steps, this phase I study will be evaluating how to accelerate the program. Thinking about phase II, on how to optimize phase II design, and to try to obtain as much hints of efficacy as possible to accelerate a potential registrational program. Great. Thanks for taking the questions, and great to hear all that's going on. Thank you, Charles. All right, next up, we have Justin Walsh from Jones Trading. Justin, take it away. Hi. Thanks for taking the questions. To start off, Actinium-225 PSMA I&T is being tested in patients in a clinical trial not associated with you guys. You have the preclinical data you had there suggesting that the renal toxicity is expected to be lower for your asset. I'm wondering if you can comment on what degree of renal toxicity would we have to see in actinium-225 PSMA I&T to give you confidence that your asset will provide a meaningful benefit to patients above and beyond that asset? Then, kind of related to this, why you think improvements in supportive care might not be good enough to have the standard Actinium-225 PSMA I&T do well in the clinic? Thank you, Justin. Very detailed question. I think that probably covers Robin, Jessica, and Neil's input here. Maybe what I'll do is I'll start with Jessica on that one, and then we can kind of move around those three. Yeah. Thank you. The I&T compound itself is the same. You know, the renal dosimetry that we saw with I&T labeled for lutetium is what we understand to be the I&T compound that's labeled with actinium. For our asset that we are developing for PSMA-62, I'm not sure if there's in essence a meaningful threshold proactively to define in terms of renal, you know, total dose. It's really identifying that sweet spot of ensuring we can move this as early as possible to stave off any potential long-term renal toxicities with as powerful of an isotope as possible, potentially with actinium. That's really some initial thoughts. Robin, I don't know if you want to, go next. Sure. Thanks, Jessica, and thanks for the question. I think renal toxicity is obviously very important, I think let's not forget that this molecule is a much better internalizer than PSMA I&T, based on what we've seen. That leads to increased retention within the tumor, based on what we've seen, and also increased efficacy. I think on an activity-to-activity basis, this ligand has the potential to deliver much more activity than it could be actinium-based activity to tumors, as well as the potential advantages of normal tissues. I think there's a twofold advantage with the PSMA-62 molecule relative to the PSMA I&T or PNT2002 ligand. Neil, did you want to add anything? I think you summarizing it quite well. I think, you know, renal toxicity is going to be a concern with these agents, particularly with the first generation PSMA-type agents. Neil, wait, it's a bit hard to hear you. We might have to get you to lean in closer or get you to dial in, but we'll come back to that question. Appreciate that, Justin. Let's continue moving the chains on the rest of the questions. Thanks so much. Next up, we have Faisal Khurshid, who should be on the line here, shortly. All right, this is Faisal from SVB Securities. Thanks for taking the question. FAP is kind of long been considered an imaging target, and translation to therapies has been a little bit more tempered. Can you talk about the reasons for this in the landscape externally, and how you see your FAP program as differentiated from the other attempts out there? Sure. Thank you, for the question. I'll get Robin to start on that one, and then we can, move over to Jessica. Thanks, Joe, and thanks for the question. I think, you know, I agree with what you stated. I think we've seen beautiful imaging data based on FAPI PET, and that those ligands existed or those agents were moved into the clinic first. I think if you think about what you require for a radioligand to be successful from a therapeutic standpoint, it's really driven by: where does your radioligand go, and how long does it stay there for? The criteria for a good imaging agent is different than the criteria for a good therapeutic agent. With some of the early agents, where we saw beautiful imaging, we know these agents do not retain in the tumor long enough to deliver a large dose, particularly with isotopes like lutetium, which have a half-life of around, you know, six and a half days. We think that really, that radiation dose or absorbed radiation dosage is key, and we haven't seen that with the 1st generation ligands. You know, we're in the clinic now. What we saw in the animal models with our ligand was that we had good retention, superior retention to what we were seeing with other agents. You know, our hypothesis is really is that we're gonna be able to deliver a larger absorbed radiation dose based on some of the work we're doing in our FAPI ligands. Yeah. Do you want to add anything? I think you said it perfectly. I mean, what it comes down to me is just how quickly we can get radiation to the tumor and as direct as possible. I think that's what you alluded to as well, and that's where the next generation compounds are optimizing that. Thanks, Robin. Got it. Thanks. If I could ask one, on PSMA in the PNT2001 program, could you talk about how you see competition in this space, both generally and for the alpha emitters? What gives you confidence that PNT2001 is well positioned, especially given the timing? Like, how much better do you have to be given the timing gap between you guys and other programs that are already in the clinic? Yeah, excellent question. There is, as you know, some competition coming forward with actinium I&T and some Actinium- 617 work. Although that isn't as advanced as, you know, I think we would, where we don't think we can catch up, definitely. I'll flip this over to Jessica to talk a little bit about that, and then how we can move quickly in that space, and Robin can add some color on the differences here and why we really believe PSMA-6 2 is going to win. Yeah. Thanks, Joe. I think this is something that we're thinking about constantly on the development team, and challenging ourselves with. How do we stay at the front of actinium PSMA moving forward? I think it's going to come down to just experience, relationships with the, you know, the agency to understand, you know, what is the right development plan to propose that could accelerate the review. And ensure proper data collection can help characterize the candidate as completely as possible, with a very well-informed overall program. I think our experience really, just the team in general, is really poised to do that. We also have forecasted the importance of actinium and have really great supply agreements in place to help accelerate that. I think all in, it's just, it's at the forefront of our minds to not take for granted the competition and just move as quickly as possible, with a very strategic and creative and careful development plan. I'll turn it over. I think, Joe, you mentioned Robin? Yeah, Robin, maybe. Yeah. You can just touch on the differences between the compounds that we see. Yeah, thanks. Before I mention that, I just want to remind everyone that actinium decay is very complicated. You have many daughters, where these daughters go matter, both from an efficacy and safety standpoint to the patient. That's really why we focused on developing a hyper-internalizing ligand, because when this ligand brings the actinium inside the cell, that actinium is now, we think, trapped inside the cell, and you have less opportunity for redistribution of those daughters. We really have a lot of conviction in the science of the PSMA sixty-two ligand relative to the first generation ligand, such as PSMA I&T and PSMA-617. I think, if we think about it scientifically, we have a lot of conviction that there will be advantages, and what we've seen pre-clinically suggests there are meaningful advantages with the ligand we've chosen to bring forward with actinium. Excellent. Yeah, we'll continue to move on, because we've got a good queue here. Next up will be, Rahul Sarugaser from Raymond James. Your line should be open here shortly. Thanks, Daniel. Can you hear me all right? Yes. Yes, please go ahead. Terrific. Thanks, Joe, and team. Thanks for taking our questions. The first one's on the SPLASH trial and actinium data and of course, now with, you know, pursuing, you know, pre-taxane treated patients. I believe there was a slide earlier that was looking at potentially moving further upstream, and I just wanted to clarify, is that with the PNT2002 molecule or, you know, can we maybe sort of resolve a little bit in terms of the outcomes from the SPLASH trial and second line treatment, and then how, you're developing strategies to move potentially upstream and potentially into first line? Great. I can address a little bit of that, and I'll turn it over to Jessica. The current development for SPLASH sits post ARPI, that's where ahead or pre chemo, kind of in that space there. That's where the SPLASH trial is designed to generate the indication. The subsequent development is in Lantheus' hands for that compound, so we can't co-comment on subsequent development there. Where our development with our 2001 assets move in is post lutetium and then into that oligometastatic biochemical recurrence space. That's all, that expansion and the discussion we had today is all focused with L1. I'll turn it over to Jessica to comment on the rest of your question. I think you covered most of it, Joe. Please let me know if there's anything that was missed. I was going to say the same thing, that Lantheus is responsible for lifecycle management of PNT2002, and I think the slide that was reflected was representative of our plans for PNT2001 or our PSMA- 62 compound, and that is also demonstrated with the trial design in a very early setting. And we're discussing with many investigators interested with the product to even evaluate earlier lines of therapy as well. Perfect. That's a really helpful clarification. My second question is somewhat quick. In terms of actinium supply, there was, of course, the recent investment partnership done. Sorry, forgive me I forget the name. Can we speak to further consolidation. With IONETIX. Thanks. Thanks, Daniel. Yes, further consolidation of POINTs of access to actinium as it continues to drive down the, you know, the actinium product path. Yes, I'd say, and I'll turn this over to Justyna in a moment, but our focus as we look at to actinium suppliers, we don't have an intention right now to internalize this. At all. It's really establishing relationships with those suppliers that we believe are true leaders in the space, both in advancing their technology, but also advancing it to the scale that we need. That's the selection of IONETIX was around that. Our work with TerraPower has been focused on that as well. Our recent also contract with Eckert & Ziegler. We also have other contracts with NorthStar that these are suppliers that are coming on in the future. What we want to do is secure suppliers immediately to support the One program. I'll turn it over to Jessica to add just a little bit more color around how we look at those suppliers. You know, with an emphasis that you'll need to establish arrangements with a number of suppliers in this space just because it's new and emerging. You don't want to kind of put your, all your eggs in one basket there, but I'll turn it over to Justyna to talk a little bit more to this. Yeah, thanks, Gerald. I think you're right, that the key is redundancy, and we stressed that through the presentation that no matter what isotope, redundancy is key, making sure we have multiple suppliers. Through the partnerships that we've established with IONETIX and NorthStar and TerraPower and Eckert & Ziegler, it's also kind of stratifying all the different technologies that are out there right now for the potential production of actinium. Looking at cyclotron-based production as well as DOTATATE-based and generator-based, and looking at, you know, those different isotope, starting isotopes, be it radium or thorium. We're kind of stratifying all that to ensure that we have supply as these technologies mature. Great. Thanks so much for taking our questions, and thanks again for putting on such an informative day. Thanks, Rahul. Next up, we have Jeff Jones from Oppenheimer. Your line is open. Great. Thanks, Daniel, and thanks, guys, for putting on the event. I guess first question, my understanding is that FAP is expressed both on tumors and on cancer-associated fibroblasts. Can you clarify if the indications you've selected for study in the clinical trial, if the overexpression you're talking about of FAP is in the tumor or the tumor-associated fibroblasts? How you think about the use of lutetium versus actinium, depending on how you see that expression playing out? Okay. Actually I'll turn this over to Robin to address this, probably Jessica will come in after. Yeah. Thanks. Thanks for the question. I think that's a really important question. As you can imagine, there's or as you know, we don't have to imagine that there's differences in pathway with lutetium decay versus actinium decay and how far the particles go, and so the architecture of the microenvironment likely matters. I think in, if you think about Frontier, we have, you know, sarcoma in there, which is reported to have FAP expression on the tumor cells directly as well as on the stromal fibroblasts, whereas tumor types like pancreatic cancer, which is also in there, probably more enriched in tumors where the FAP expression is predominantly on the cancer-associated fibroblasts. I think we have examples of both. I think there's definitely still a lot to learn, and I think we will continue to learn from our trial. I think you could imagine with actinium decay, you're likely to have a more local effect onto where your ligand's located, and you may have a differential impact on delivery of the radiation into the tumor cells versus radiation into the fibroblasts. There's plenty of preclinical data and translational studies supporting that both of those may have potent therapeutic effects. It's something we're hoping to learn more about. I think there could be differences, but at this time, we don't have data to answer those questions directly. Jessica, do you wanna add anything? Thank you. It was very thorough. The only thing maybe to add is that there was really three core principles that we used in narrowing down the tumor types, because there was many options. Those principles were scientific principle, or like a scientific pillar. We had a regulatory pillar and a commercial pillar. Scientific pillar was one of our primary drivers, and we evaluated that exact question and did include in our tumors of choice, those that showed actual expression on the tumor as well as the stroma. Some of our earlier slides did represent this that we have had included, I think, in our investor decks. Though, as Robin mentioned, there is a lot more information that's still needed. We're really in very early stages of FAP study, of studying the study of FAP, and so more tissue studies are required, and these are all initiatives that we are working on here at POINT as well. Great. Thank you. If I could ask one more question, Daniel. We're gonna just get everyone to get a couple quick ones in, if that's okay, Jeff. All right. Thanks so much. Okay. Next up, we have, Kemp Dolliver from Brookline. Your line should be open here shortly. Thank you, Daniel, thank you for taking my questions. The LuMIERE trial recently had some changes where the enrollment target has increased, nearly doubled to 300 subjects, and there was also a change in one of the primary endpoints to focus on disease control rate instead of overall survival. You know, what are your observations regarding what you see Novartis doing in, you know, with their asset? How may that influence how you'll advance your program? Sure. Thanks for the question, Ken. It's hard for us to comment on Novartis's developmental strategy and the rationale for those changes. I think what it probably demonstrates is a continued interest and the need for continued understanding in the space, of how these compounds are going to work, how they should be developed, and their ultimate application long term. I think that just speaks to that this isn't like PSMA and SSTR, where there seemed to be a very straightforward development pathway, a lot of that done over more than a decade, and nobody really saw that development happen. I think what you're seeing now is development happening out in the open, by companies. This is just a reflection of getting to know these, this target better, getting to know this target across indications better. We're not reading too much into that. It's really, again, their development pathway is their development pathway, and we've continued to focus on what we're doing to get an understanding of different indications, get an understanding of the dosimetry piece. Again, we'll be bringing forward that dosimetry data in the first half of 2024 with all the learnings that we have taken from this. I think FAP is going to be definitely a different development pathway or less straightforward development pathway than we've seen for PSMA or SSTR. Jess, I'm not sure if you wanted to comment on any of that. Just that it's hard to speculate, on that, but, you know, expanding for more patients, is really just showing the, you know, the importance of collecting more data, and evaluating disease control, with ORR is very important in understanding any type of, potential, you know, signal. I think it's, you know, overall promising for the field and the study of FAPs, 'cause what's important is to share, you know, our data to advance, all of our products, you know, and improve upon them. Ken, if you have another one, otherwise, go to next in line. One quick one that relates to Actinium-225 with, potential levels of Ac-227 in it. What are your thoughts on the supply that's available that may have Ac-227 in it? Are you comfortable with the what you've seen so far, if any, and take it from there? Sure. I think this gets back to the similar debate with carrier-added lutetium versus no-carrier-added lutetium, where you're dealing with a long-lived isotope, lutetium-177m in the carrier-added. We made a choice at that time to stay away from that because of the complications that it adds at the clinical site with managing waste. We saw that as a barrier, and when we started our SPLASH trial actually a few years ago, that was one of the big questions and concerns, is they wanted to ensure that we're only going to deliver no-carrier-added lutetium because it's easy to manage within their system. We carry the same philosophy forward into actinium and that's focused on finding or getting access to supply of actinium that does not contain Actinium-227. That's the goal of the program. We don't see ourselves deviating from that at all, because we do believe that that will add complications at the clinical site. That will lead to more bottlenecks at the clinical site, and only limit this field. There's a ton of suppliers now of Actinium-227, actinium, and, you know, I think continued use of that will pave a pathway forward where we won't need to use any of the actinium, the actinium that contains 227. Again, we think that long half-life of over 27 years is going to be very limiting to those clinical sites in managing that waste and adds headaches that we do not need to add today or tomorrow. Justyna, I'm not sure if you wanted to touch on anything there. Joe, I think you said it very well. I think everyone that we have agreements with are all striving for Actinium- 227 three, Actinium-225, and are continuing on that path. Thank you. Okay, next up we have Nicole Germino by phone. Your line should be open. Let us know if you can hear us. If not, we'll try. Hey, hey, Daniel, can you hear me? Yes. Okay, you're live. Hey, great. Great, thanks for taking my question. Just a quick question on PNT2001 for PSMA. Can you talk about the salivary tox that you're seeing versus the competitive landscape? Sure. This is for the actinium program, the actinium PSMA program? Yeah, that's correct. Yeah. We have not been in patients yet, so we don't have any experience, human experience with salivary tox. Of course, in the animal studies, it gives you limited experience with what actually manifests there. I'm not sure, Robin or Jessica, if you can comment on any of the data you've seen out there, with the other ligands, not with ours, related to salivary tox in the actinium space? Not sure who wants to jump on that one. Maybe I'll throw Jessica under the bus on that one. Yeah. Yeah. Joe, I'm happy to... Neil? Yeah, go for it, Neil. Yeah. Yeah, no problem. Look, I mean, I think what we know about what's happening in Europe with the current actinium-based PSMA products, is that there is considerable salivary toxicity, and people are trying to mitigate that with a variety of strategies. And, you know, I think our general philosophy is end of life patients would probably bear that degree of, you know, of AE-related toxicity. However, I think we're, if we're talking about bringing treatments earlier into the disease, then, and where patients have a longer natural history of life, then that can become more problematic. That's why we're very excited and very determined to bring more novel ligands that either will have less salivary toxicity or a higher, if you will, potency with respect to, for example, internalization in the cancer cell, and therefore perhaps we could reduce dose or number of cycles. Okay, great. Just one quick question on the FAP program. Can you talk about how you're thinking through the monotherapy versus any potential for combination strategies and how that timeline's going to look? Yeah, we can comment on that. I think we have some preclinical data that's out there that's very compelling. We don't, haven't disclosed any timelines on when we'd be looking at combinations yet, but we can speak to some of that preclinical data that's, you know, very exciting. I'll turn it over to Robin for that. Thanks, Joe, and thanks for the question. What we've shared is experiments with our lutetium labeled PNT6555 with checkpoint inhibitors, in this case with anti-PD-1. We've run this in animal models that express low level of FAP and are otherwise resistant to monotherapy anti-PD-1, where we see substantial regression as well as long-term survival when we apply these two together in combination. Which really fits the hypothesis that radiation is an immune stimulant or can act as a really adjuvant or agonist, and combine really nicely with checkpoint inhibitors. Particularly, what was compelling with this model is that FAP expression was not high, anti-PD-1 on its own, had no impact to tumor growth, but combining them together had quite a substantial impact. I think we're very excited about just speaking sort of mechanistically. I think we're excited about both the potential for combination effects as well as monotherapy. We've explored both preclinically. Jessica, I don't know if you'd like to add anything. Yeah, no, that was very, very complete. It was also a consideration when we're identifying our tumor types, you know, how we could evolve our development plans for the potential of combinations as well. we'll continue to move along. Thanks, Nicole, for your question. Next up, we have Alex Ramsey from William Blair. Your line should be open. Hey, everyone. Thank you so much for holding this session and for taking my question. I had another question about actinium. A bit earlier, I think, Robin was talking about the complicated decay chain for actinium and how that makes it especially important that, like, the new ligand for PSMA is very intensely internalized to keep those free daughter particles kind of in the tumor site. I was just curious, given the complicated decay pattern, if there's a risk of the free daughter particles being in the patient or before it reaches the tumor, either from decay, you know, during circulation or even before it's injected, or if that risk is largely minimized given the long half-life. All right. I'll turn that over to Robin, and then probably Justyna to comment. Sure. I can comment based on some of the... it is complicated decay. I think after you have the first decay of actinium, that is, it is essentially lost or breaks up, it's no longer chelated, which is why we like the internalization. as you POINT out, actinium has a relatively long half-life. as you inject this into a patient, or in our case, we have, we have animal data, we also know it clears very, very quickly. That's one of the things we like about this molecule. It clears very, very quickly, except for sites where PSMA is expressed, such as prostate tumor cells, where it's internalized, and then that is retained within the tumor. You catch that full decay, but otherwise you get rapid clearance via the kidney into urine, which is what you'd expect for a molecule like this. You don't have, you know, persistent circulating molecule that's labeled actinium. It sticks to the tumor and otherwise really flushes rapidly out of normal systemic tissues and systemic circulation. Justyna, did you want to add anything to that? I think Robin touched on the key part here, is that, you know, you want to be able to internalize that before that decay happens and you have potential escape of the isotope from the ligand, and then that rapid clearance again before that decay happens and it has the potential to escape that ligand as it's circulating through the body. With the longer half-life and rapid clearance, and of course, internalization, we're looking to mitigate that. Okay. Alex, do you have another or are we moving on? Oh, sorry. I have just one other quick one. You mentioned, like, moving on to other isotopes essentially beyond actinium and lutetium. I think in the past you've mentioned terbium. I was just kind of curious if you're still looking at this? I think you've mentioned that one of the benefits is the Auger electrons are also emitted. I was just wondering if that's the only benefit and what other benefits there are and for Auger electrons, specifically, what clinical data there is that demonstrates the benefits of this type of emission? Mm-hmm. Yeah, the data out there on Terbium-161 is somewhat limited due to an extremely tight supply chain on that. That's driven actually out of what your radiation reactor, which is Gallium-160. That has limited a lot of human or clinical data that's been out there. The preclinical data is interesting, and, you know, does show that there could be a difference that Auger could bring. Largely, if you look at everything else, that terbium is very similar to lutetium with the addition of that Auger. There are some studies, and I'll flip it over to Robin here to speak to. We continue to explore the opportunities with that isotope as well as others. Again, we look to fill our toolbox of isotopes as full as we can, evaluate those in discovery and developments, bring forward the ones that we think are going to generate compelling clinical data. Terbium, again, very interesting, very, very early on clinically. Robin, could you speak a little bit to the preclinical data that we're seeing? Yeah. That is strong in academia. Yeah, I think, you know, there's a really nice study that came out of Paul Scherrer Institut from Cristina Müller's lab, that showed that terbium was particularly potent at killing cells when it was attached to ligands that localize on the membrane. These particular studies were done with SSTR2 agonist and antagonist, you saw really the biggest difference in sort of killing potential between lutetium versus terbium when you had ligands that localized on the membrane. I think this is just, you know, a small piece of data. Hopefully, there's much more data that comes forward to help us understand this. I think it's all about identifying based on the characteristics of your ligand and the characteristics of the patients you intend to treat with your ligand, what is the ideal isotope. Because there's differences in isotopes, there's differences in ligand properties, and there's different risk-benefit profiles for these kinds of therapies in patients. We really want to understand that scientifically and match in a, in a, in a rational way, the right isotope to put on the right ligand for the right patient population. Very helpful. Thank you so much. Thanks. Next up, we will have Ajay Volasimaw from Jefferies. Your line should be open here in one second. Hi, all. This is Ajay, on for Andrew Tsai. Thanks for hosting. I'll keep this brief. Could you comment a bit more on the commercial side for both PNT2004 and PNT2001? You know, PNT2004 TAM assumptions and timelines to market, and for PNT2001, sort of digging further into the competitive landscape here, how do you see the market opportunity in relation to PNT2002, should both succeed in getting to market? Thanks. Yes, we haven't provided direct TAM assessments for 01 or, sorry, for 04, mainly because we're still in the development phase, and you could look at this as being really you could go after any cancer that expresses FAP. We're gonna learn a lot more in the developments that will likely narrow that down. An incredible addressable market out of the gates. I think as we start to read this down and learn more, we're gonna see that get narrowed into some more focused indications or more focused combinations, and find out where it works and where it doesn't work. Obviously, a ton of potential today, but we've got to weed that down. We haven't spoken to that directly, but you can see that there's potential here in pancreatic cancer, which is an incredible high net need. That's a focus for us, as well as where could we apply this against that target, where there's incredible unmet need and that this could create options for patients. That's our focus there, as well as seeing where we can expand that into other areas where combinations may make sense. On the 01 patient population, we have in this presentation, and then in our investor deck, have guided to the size of the potential markets in the post-lutetium space, which we've guided in our deck as being about 16,000 patients that fill that space. Again, you would have to funnel that down for the patients that would be addressable here. As well, in the BCR, or oligometastatic hormone-sensitive population, you know, that's quite large, 214,000 patients. Obviously, you're gonna have some funneling down there as, you know, certain criteria, and we'll learn more in clinical development where this will be well suited to patients and obviously not well suited to patients. Again, very large markets. The BCR and metastatic space is significantly larger than what we're seeing in the SPLASH patient population or anything that's moving into the metastatic space. A real large market opportunity. Again, we'll learn more in clinical development exactly how or what patients within that will benefit from this drug. Thanks for that. Question, Ajay. Do you have one more, or we move on? We've got one more, a few more minutes of time here. Oh, I'm good. That's very helpful. Thanks, Dan. Okay, thanks. Next up, we have Hangfei F u from TD Cowen. Your line should be open. Hi, can you hear me okay? Yes. Go ahead. Thank you. This is a really informative session. My question is regarding your recent ask for activity, the early activities being PSMA therapy with both alpha and beta emitters. Just want to get your general insight. The convergence, the Convergent poster? I just kind of see what's the do you like, targeting therapy with alpha and beta since your FAP program also have, alpha and beta emitter programs? Sure. Thanks for the question. Jessica, did you want to take the question on the combinations, and or the Convergent combinations with PSMA? Yeah. I mean, the ten delivery of an alpha and a beta is something that has been reported on to have potential for efficacy from our German colleagues and logical scientifically as well. This is, you know, very early data to show primarily in a design that was for safety that Dr. Tagawa pre-presented. I think that at this POINT in time, that's really all that can be shared is that there is scientific principle there. That is what was evaluated in Dr. Tagawa's study. Speaking to us, looking at the FAP inhibitor program. That isn't intended to be a combination. It's intended to be looking at lutetium separate from actinium. Right now the lutetium program's in the clinic. The actinium program is still sitting pre-clinically just so we can understand that more and how we would deploy it clinically. Nothing really to comment there from a combination perspective, that's not our intention in moving forward there at this time. Hank Spade, do you have one more? or no, that's it. Let's just go back to the top. There's just one or two more. Jeff Jones, your line should be open again from Oppenheimer. Great. Thanks, Daniel. You guys mentioned business development. Could you comment on sort of key criteria or what you're looking for as in terms of in-licensing? Definitely. We're as we look at in-licensing, of course, we're looking kind of in two areas. One is, would be technology to continue to build out our platforms that will drive our discovery programs. Making certain partnerships to develop kind of new novel ligands. We're also looking at existing ligands that are out there that have either generated very compelling pre-clinical data, but we have a real focus on phase I and phase II data. We're doing a lot of work there to assess, you know, what we can bring into POINT, leverage the skill set that we have in this team that can really drive things forward very quickly. More clinically, phase I, phase II data, pre-clinically, more platform that we can generate more lead ligands from. Appreciate that. Thank you. Okay, we'll just loop back to Kemp Dolliver for one more, and then we should be wrapping up here shortly. Daniel, can you hear me? Yes, go ahead. Great. Thank you so much. This is a wide open question. You have capital coming in over the next few years. The amount actually, you know, the exact amount is difficult to predict, but to the extent you get incremental capital, beyond your current expectations, what would you do with it? You've answered the BD question already, so let's just put aside BD, and when you look at your pipeline, where your pipeline, whether it's clinical, pre-clinical, where do you think you would put incremental investment capital if you had it available? Great question. I think part of that can be answered in that we have now expanded our campus in Indianapolis to include a second building. That's both to bring forward redundancy, but to bring forward that internal capacity for new isotopes. Isotopes that we may not have currently in the clinic, but that we may be looking to bring in. Again, build out or bring in-house our own supplies of those, which we see as being a key aspect of this business, is controlling that. That gives us the ability to deploy it there. That, of course, goes hand in hand with good clinical data. Not to repeat the business development piece, but again, tying those choices on those isotopes, obviously tie to exciting ligands, then allows us to drive a more robust clinical development program. Really that firm investment in driving those early-stage programs forward when we get, you know, exciting data to be able to move them quickly forward. For example, exciting data in FAPI, would be able to just start branching out those trials, and being very aggressive in generating phase II data. And then as well, we also have to consider that currently we're very North American-based, and as opportunities grow, looking at building out potential redundancy as we move and look into Europe. I think the focuses are ensuring the current supply chain, expanding our internal access to isotope, combined with those, driving platforms in our discovery programs. Bringing forward more ligands into new targets, not current targets that we're going after, and then bringing in, ensuring that we have that capacity to drive forward those phase I, phase II programs that we could potentially in-license. Assuming our internal programs go well, especially in the FAPI space, is being able to drive those in as many possible indications as we can. Great. Thank you. All right. Thanks so much. That concludes our.