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Presentation Session

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Hello everyone and welcome to POINT Biopharma’s Investor Day. My name is Daniel Pearlstein, Director, 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 Investors 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 and 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.

And 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 we'll 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, and Joe will then provide some concluding remarks before we commence Q&A.

So sit back and relax, and I'm pleased to introduce to you our CEO, Dr. Joe McCann.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

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 tumor with an external beam of ionizing radiation that causes that DNA damage and that cell death. But 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 iodine-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 that with 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 that's used 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 so 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. And you can see only faint amounts picked up in some organs and none in healthy tissue. And 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. And you can see that this 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.

So as I mentioned, radioisotopes have been used to treat cancer and have known to be safe and effective for over 50 years. But I wanted to provide you with some more details on why this space has lagged other modalities. So focusing on the column that shows past issues in this space, you know, these are real and have been really the driving force behind that limitation. And 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. So that really limited the amount of isotope, that pharmaceutical radioisotope, available to do clinical development, and 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. So 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 need for that supply chain. So it's limited clinical development going on, no access to commercial products, no one invested in the treatment sites to actually treat these patients. So when something came forward that that was exciting, it was only handled in very limited areas within very large hospital institutions. And this cycle continued, and there was limited investment in the space, and therefore really nothing has happened until the last five years.

So 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 3 trials, you can drive commercial products. Now we still need to continue to drive the manufacturing excellence in this space, this is an area where we're still seeing that there's some limitation, but there is now an understanding that with investment into manufacturing excellence, that will drive patient access and that will drive commercial successes of these drugs. And 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 iodine-131, so the handling landscape has changed. This has increased the willingness of hospitals to invest in these products, and 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 because they know that this is an option they want to offer to their patients that are coming through. Currently, that key example is in prostate cancer. And with a potential blockbuster indication in prostate cancer, there is now investments going into the space to bring more companies forward, creating greater shots on goal in our industry, that are going to 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.

So 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 I will 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 has built into POINT. The capacity and industry insights that we have as a team has driven efficient clinical programs from phase 1 to approval, and currently right now, as I mentioned that the tail end of completing a phase 3 trial. And 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.

So shown here is our pipeline, I'll go through it in a high level, we have our PNT2002 program, it’s a PSMA-targeted radioligand using lutetium-177. Again, this program’s in a phase three clinical trial for prostate cancer in the pre-chemo space, in metastatic castrate resistant prostate cancer patients. The top line data is expected to read out in the second half of 2023, and we’re developing it in partnership with Lantheus. The 2003 program is a DOTA-TATE based compound using lutetium, we're also developing this in partnership with Lantheus. The program 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 1 results from the lutetium-177 trial called FRONTIER will be shared in the first half of 2024. Our 2001 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 plan to bring this into phase 1 trials in the first quarter of 2024. Then 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, DNA damage response inhibitors, and chemotherapies.

So just a little bit of a highlight of the skill that is within POINT and really that POINT has, that only really a handful of companies in our space have. So remember that POINT is just over three years old, yet we have years of experience of talented staff that we've brought into the company, and what you're seeing on this slide is the result of that, those decades of experience of our staff, to drive a phase 3 clinical trial. And that's very important to recognize because this expertise, and remember we conducted this phase 3 trial during a pandemic and completed it on time from our guidance, even from the formation of the company. So in order to do that, you need that expertise, and that's the expertise that really de-risks POINT as we move forward and look at 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.

So 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 our discovery and development scientists, and we’ll become a 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 both supply chain and manufacturer.

Justyna Kelly, M.Sc. – Chief Operating Officer (POINT Biopharma)

Thanks Joe. Hello everyone, thank you for joining. My name is Justyna Kelly, and 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. So 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 and delivery of the medical isotope. And as you can see, these types of isotope shortages and supply chain disruptions are not new to the space, but 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 disruption 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 the isotope can't be produced and stockpiled on the shelves until it's needed for radiopharmaceutical production. The patient administration date is the key date that drives all activities upstream, from the point of irradiation of stable target material to produce lutetium. From that point onwards, it is critical to coordinate all activities in order to ensure that the dose arrives on time for the patients. The key element of success is establishing redundancies at the most critical time points to ensure dose arrival at the time of treatment. And since the inception of POINT, our focus has been on performing due diligence in 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 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 lutetium isotope in house. The redundancy of both external and internalized 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, Missouri University Research Reactor for target irradiation, and the Belgian Nuclear Research Center for lutetium separation and purification processes as well as target irradiation. 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. So 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, target irradiation, 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, and 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, and 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.

And now onto manufacturing, where we will talk about the key infrastructure pieces of our platform. POINT has established 2 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. And we have 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, CORE1, or building one, is where we currently operate, and we have 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. CORE1 has provided over 80,000 square feet where we continue to build out operations in a phased approach. CORE2 provides an additional 100,000 square feet for future production expansion.

And 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 8 hour driving radius from the site, and 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 a shell, we have been planning for commercial success based on the modality of radiopharmaceuticals and not any one particular program. So 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 buildout 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.

So the building within a building concept that you see here allows us to scale and expand while maintaining our current operations. Clean room 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 the shipment of isotope which is ordered specifically for each batch of radiopharmaceutical product 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. So by producing our own no-carrier-added lutetium in house, we control this critical aspect of radiopharmaceutical production. We are 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. So we just recently leased this building located right next door. This space, this is the second building shown here, provides an additional 100,000 square feet for future expansion, including additional office space and parking. We plan on taking a very similar approach in the build out of the production space in the second building, with that building-within-a-building design that will allow us to scale operations as needed.

And 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. So with that, I will pass the spotlight on to Jessica Jensen and Robin Hallett to discuss next-generation radioligand therapies. Thank you everyone.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

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. However, 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 spec diagnostic ProstaScint 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, and this is where we believe we can transform the disease landscape. It is with actinium-225 PSMA-targeted radioligand therapy that we hope to make a difference. As you know, we have a very talented and experienced uro-oncology team at POINT and 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 occurrence or oligo-recurrent 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. And 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. And we will discuss more about this phase 1 study shortly. I'll now hand this to Robin Hallett.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Thanks Jessica. 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 Professor 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 hyper internalizing 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 all succumbed to disease within 60 days post injection, whereas all PSMA-62 treated mice were still alive at this time. Back to you, Jessica.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Thanks again, Robin. And 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 1-2 multi-center study that will commence with the phase one 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 1 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 megabecquerels per meter squared or approximately 14 megabecquerels. 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 1 study is focused on identifying a recommended phase 2 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. And 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.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

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 the targeted radioligand is successful is where does the radioligand go and how long does it stay there for, as 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 tissue.

POINT is working on a number of new early stage programs and we wanted to provide some insight into our philosophy on this process. For all new program concepts, we ask ourselves the questions: 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 in the therapeutics that 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. 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. However, 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 fat and rapid clearance for normal tissue with sufficient tumor resonance 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-labelled PNT6555, is extremely efficacious in preclinical animal models. It shows dose dependent anti-tumor 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 labeled 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. And finally, defining optimal dosing regimens or strategies that take advantage of the fast clearance and reduce normal tissue retention of FAP-targeted radioligands, and isotope selection to maximize the radiation absorbed dose by tumors. Back to you, Jessica.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Thanks again, Robin. We began the phase 1 FRONTIER trial in July 2022 and have enrolled 7 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 the 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 2 dose in this phase 1 study, and I will review various endpoints presented on the next slide. We are currently at our highest dose level screening patients for 12 gigabecquerels with the 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.

And in this trial you see presented here very robust radioligand therapy, exploratory and secondary objectives. With our current cohort under evaluation at 12 gigabecquerels, we expect to present data on these objectives in the first half of next year. And in totality, our experience advancing our phase three trial with the FDA has enabled strategic development considerations for this phase 1 first in human trial with a novel target. And I'll now turn it over to Dr. Neil Fleshner.

Neil Fleshner, M.D. – Chief Medical Officer, Co-Founder (POINT Biopharma)

Thank you, Jessica. My name is Dr. Neil Fleshner, Chief Medical Officer and Co-Founder at POINT. And 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. And this translates in the U.S. to approximately 20 million nuclear medicine procedures being done every year. To date, most of them, on the diagnosis phase, but 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, 2500 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. And 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 to 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. And these scans could then be used for selecting patients for radioligand therapy, because of course if the ligand lights up on imaging and that patients is generally a good candidate for radioligand therapy. But you could also imagine newer realms of guided therapeutics such as guided surgery and guided radiotherapy that also involve the same tracers. So we really foresee a feedback loop between radioligand therapy and radio ligand based imaging as this whole field of theranostics continues to expand.

Now 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 lined 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 radiopharmacies and treatment centers. This map that you see below simply has pins on radiopharmacies and treatment sites for radioligand treatments across America. And this continues to grow, and this is continues to expand largely in treating the large burden required for prostate cancer and neuroendocrine cancers. And 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 could see a screen capture from the Government of Canada around lessons learned from the shutdown of a local nuclear reactor, and you can see in the red bullet that hospitals and radiopharmacies should secure sources from more than one supplier. And 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 technecium and molybdenum shortages some years ago and we feel that the same practices will likely apply to therapeutic isotopes as well.

And 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. And we think that this is important because we feel it will 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 application. And we're very cognizant of this 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.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Thank you, Neil, and thanks everyone in our audience for your attention today. Before we move on to Q&A, we want to highlight a few things for you. So 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 and we are using our unique capabilities and internal expertise to develop potential best in class agents in large indications with high unmet need.

So 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 3 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.

And 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 one data from our FAPi program, which we expect to share in the first half with 2024, a clinical data update for 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 a $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 and I'll now turn it over to Daniel to host our Q&A.

Q&A Session

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Thank you, everyone, for taking the time to participate today. We really appreciate it. We're just going to 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.

Charles Zhu (Guggenheim Securities)

Hey, 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 histology for expansion cohorts or maybe something like an SUV cut for tumor by tumor or by radioactive uptake? Or is some – something else? Thank you.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Thank you, Charles and thank you for attending. I'll – actually, turn that over to Jessica to add some more color there.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

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.

So 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 backgrounds And then, optimizing it to that right balance of not excluding too many patients, but ensuring the right patients are included.

So, as of right now, we're using liver as our background. That could evolve to a blood pool background. And so, we look – 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. So, 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.

Charles Zhu (Guggenheim Securities)

Great. Thanks. Yes, that does it. Thanks for that useful color. Maybe one more from me before I hop back in the queue. I've 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?

And 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.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Okay. Great. I'll let Jessica take that one as well.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Thanks. Thanks, Charles and Joe. Yeah. So, in our Phase 1, we are setting two populations as a reminder, mCRPC and BCR. In the BCR setting, we are not – our ultimate goal is to try to stave the use of hormones. And we are evaluating this prior to ADT initiation. But in the mCRPC setting, once a patient does start ADT, you typically never take them off ADT. And so, ADT will be used in that – in concomitantly with that – within that population.

And then, as we're evaluating the full development plan and pathways for next steps, this Phase 1 study will, we're going to evaluating how to accelerate the program thinking about Phase 2, how to optimize Phase 2 design and to try to obtain as much hits of efficacy as possible to accelerate a potential registrational program.

Charles Zhu (Guggenheim Securities)

Great. Thanks for taking the questions and great to hear all that's going on.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

All right. Next up, we have Justin Walsh from Jones Trading. Justin, take it away.

Justin Walsh (Jones Trading)

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 that, 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. And then kind of related to this, why do you think improvements in support of care might not be good enough to have the standard actinium 225 PSMA-I&T do well in the clinic?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Thank you, Justin. Very detailed question. So I think that probably covers Robin, Jessica and Neil's input here. So maybe what I'll do is I'll start with Jessica on that one and then we can kind of move around those three.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Yeah. Thank you. Well, the I&T compound itself is the same. You know, the renal dosimetry that we saw with I&T label that we saw with I&T-labeled to lutetium is what we understand to be the I&T compound that will be – that's labeled with actinium. But for our asset that we are developing for PSMA-62, I'm not sure if there is, in essence, a meaningful threshold proactively to define in terms of renal 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. So, that's really some initial thoughts. Robin, I don't know if you want to go next.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Sure. Thanks, Jessica, and thanks for the question. I think renal toxicity is obviously very important, but I think let's not forget that this molecule's a much better internalizer than PSMA I&T based on what we've seen. And that leads to increased retention within the tumor based on what we've seen and also increased efficacy. So, I think on an activity-to-activity basis, this ligand has the potential to deliver much more activity, that it could be actinium-based activity to tumors, as well as the potential advantages of normal tissues. And so, 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?

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Appreciate that, Justin. Let's continue moving the chains on the rest of the question. So, thanks so much. Next up we have Faisal Khurshid, who is – should be on the line here shortly.

Faisal Khurshid (SVB Securities)                                                                                                                                                                                      

All right. This is Faisal from SVB Securities. Thanks for taking the question. So FAP has long been an imaging target and translation to therapy has been a little bit more tempered. Could you talk about the reasons for this in the landscape externally and how you see your FAP program is differentiated from the others out there?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Sure. Thank you for the question. I'll get Robin to start on that one and then we can move over to Jessica.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

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 and that those ligands existed for those agents who are moving into the clinic first. And 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? And the criteria for a good imaging agent is different than the criteria for a good therapeutic agent. And so with some of the early agents we saw beautiful imaging, we know these agents are not retained in the tumor long enough to deliver a large dose, particularly with isotopes like lutetium, which have a half-life of around 6.5 days. And so we think that really that radiation dose or absorbed radiation dose is key. And we haven't seen that with the first 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. And so, you know, our hypothesis really is that we're going to be able to deliver a larger absorbed radiation dose based on some of the work we're doing in our FAPi ligands. Jessica, do you want to add anything?

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

I think you said it perfectly. I mean when it comes to me is just how quickly we can radiation to the tumor and as direct as possible. And I think that's what you alluded too as well and that's where the next generation compounds are optimizing that. Thanks, robin.

Faisal Khurshid (SVB Securities)

Got it thanks. And then if I could ask one on the PSMA and the PNT2001 program, can you talk about how you see competition in this phase both generally and for the alpha emitters? And 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 at the clinic?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yes, okay, excellent question. There is, as you know, some competition coming forward with actinium I&T and some actinium PSMA-617 at work. Although that isn't as advanced as, you know, I think we would – where we don't think we can catch up definitely. But 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-62, is going to win.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

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. And I think it's going to come down to just experience relationships with, you know, the agency to understand, you know, what is the right development plan to propose that would – could accelerate the review. And ensure a proper data collection which can help characterize the candidate as completely as possible with a very well informed overall program. And 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. So I think all in, is 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. And so I'll turn it over. I think, Joe, you mentioned Robin?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yeah, Robin, maybe you can just touch on the differences between the compounds that we see?

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Yeah. Thanks. And I just – before I mention that, I just want to remind everyone that actinium decay has been very complicated. You have many daughters, and all of these daughters still matter both from an efficacy and safety standpoint to the patients. And that's really why we focused on developing a hyper internalizing ligand, because when this ligand brings the actinium and die inside the cell, that actinium is now, we think, trapped inside the cell. And you have less opportunity for redistribution of those daughters. And so we really have a lot of conviction in the science of the PSMA-62 ligand relative to the first-generation ligands, such as PSMA I&T and PSMA-617. And so I think if we think about it scientifically, we have a lot of conviction that there will be advantages. And what we've seen preclinically suggest there are meaningful advantages with the ligand we've chosen to bring forward with actinium.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Yeah. We'll continue to move on because we've got a good queue here. Next up will be Rahul Sarugaser from Raymond James. So your line should be open here shortly.

Rahul Sarugaser (Raymond James)

Terrific. Thanks, Joe and team, thanks for taking our questions. So the first one is on the SPLASH, trial and in the event data. And of course, now with pursuing a pre-taxane treated patients and I believe there was a slide earlier treated patients and 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 O2 molecule or, you know, can we maybe sort of resolve a little bit in terms of the outcomes from SPLASH trial and second line treatment and then how you're developing strategies to move potentially upstream into potentially in the first line?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yes. So, I can address a little bit of that, and I'll turn it over to Jessica. So, the current development for SPLASH sits post ARPI. So, that's where ahead after chemo, so kind of in that that space there and that's where PNT2002 or that's where the SPLASH trial designed to generate the indication. The subsequent development is at Lantheus' hands for that compound. So, we can't comment on subsequent development there where our development with our PNT2001 assets moving at post Lutetia and then into that, we'll look at metastatic biochemical recurrence base. So, that's off of that expansion. And the discussion we had today is all focused with the one, and I'll turn it over to Jessica to comment on the rest of your question.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

I think you covered most of it, Joe. So, please let me know if there's anything that was missed. But 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 compounds, and that is also demonstrated with 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.

Rahul Sarugaser (Raymond James)

Perfect. That's a really helpful clarification. And so, my second question is somewhat quick. In terms of actinium supply, there was, of course, the recent investment partnership done, sorry, I forgot the name. So, can you maybe speak to further consolidation the recent investment partnership done. I'm sorry. Forgive me. I forgot the name. And so, could you maybe speak to a further consolidation of...

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

...with Ionetix, with Ionetix.

Rahul Sarugaser (Raymond James)

Great – thanks, Daniel, yes – and a further consolidation in – of POINT's access to actinium as it continues to drive down the actinium product?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yes. So, I'd say, and I'll turn this over to Justyna in a moment but, our focus, as we look at to actinium suppliers. So, we don't have an intention right now to internalize this at all. So, it's really establishing relationships with those suppliers that, we believe, are true leaders in the space, both in advancing our technology, but also advancing it to the scale that we need.

And so, that's the selection of Ionetix was around that and our work with TerraPower has been focused on that as well. And then, our recent also contract with Eckert & Ziegler. And we also have other contracts with Northstar that – and these are suppliers that are coming out in the future. What we want to do is to secure suppliers immediately to support the PNT2001 program. And I'll turn it over to Justyna to add just a little bit more color around how we look at those suppliers but, you know, with an emphasis that you – you'll need to establish arrangements with a number of suppliers in the space just because it's new and emerging. So, you don't want to kind of put your – all of your eggs in one basket there. But I'll turn it over to Justyna to talk a little bit more to this.

Justyna Kelly, M.Sc. – Chief Operating Officer (POINT Biopharma)

Yeah. Thanks, Joe. And so, I think you're right that the key is redundancy, and we've stressed that through the presentation that, no matter what isotope, the redundancy is key and in making sure that we have multiple suppliers. But through the partnerships that we've established with Ionetix and Northstar and TerraPower and Eckert & Ziegler, it's also kind of stratifying all of the different technologies that are out there right now for the potential production of actinium. So, we're looking at cyclotron-based production, and as well as accelerator-based and generator-based and looking at you know, those require with different starting isotopes, be it radium or thorium. So we're kind of a stratifying all that to ensure that we have supply as these technologies mature.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Thanks Rahul. Next up, we have Jeff Jones from Oppenheimer. Your line is open.

Jeff Jones (Oppenheimer & Co.)                                                                                                                                                                            

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 and then how you think about the use of Lutetium versus Actinium depending on how you see that expression playing out?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Okay. So I shall turn this over to Robin to address this and then probably Jessica will come in after.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

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 FAP like with the Lutetium decay versus Actinium decay and how far the particles go. And so the architecture of the microenvironment likely matters.

I think if you think about FRONTIER we have you know sarcoma in there, which is reported to have found expression of 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 cell associated fibroblast.

So I think we have examples of both. I think there's definitely still a lot to learn. And I think we have – we will continue to learn from our trial. I think you could imagine with actinium decaying, you're likely to have a more local effect on to where your ligand is located. And you may have a differential impact on delivery of radiation into the tumor cells versus radiation to fibroblasts.

There's plenty of preclinical data and translational studies supporting that both of those may have potent therapeutic effects, so it's something we're hoping to learn more about. And – but I think there could be differences. But at this time, we don't have data to answer those questions directly.

Jessica, do you want to add anything?

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

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. And these principles were scientific, scientific principle – like a scientific pillar. We had a regulatory pillar and a commercial pillar.

And 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. And some of our earlier slides did represent this that we have had included, I think, in our investor decks.

And so, though, as Robin mentioned, there is a lot more information that's still needed. We are – we're really in very early stages of fat study, studying the study of fat. And so, more tissue studies are required. And these are all initiatives that we are working on here at POINT as well.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Thanks so much. Okay. Next up, we have Kemp Dolliver from Brookline. Your line should be open here shortly.

Kemp Dolliver (Brookline Capital Markets)

Thank you, Daniel. And 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. What are your observations regarding what you see Novartis doing with their asset and how is that – how may that influence how you advance your program?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Sure. Thanks for the question, Kemp. So it's hard for us to comment on Novartis' development 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, and how they should be developed, and their ultimate application long term. So I think that just speaks to that this isn't like PSMA and SSGR where there seem 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 the development happening out in the open by companies. And so this is just a reflection of getting to know this target better, getting to know this target across indications better. And so 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 in different indications and get an understanding of the dosimetry piece. And, 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. But it's a – and in fact is going to be a definitely a different development pathway or less straightforward development pathway than we've seen for PSMA or SSTR. Jessica, I'm not sure if you want to comment on any of that?

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Just that it's hard to speculate on that. But, you know, expanding for more patients is really just showing them the importance of collecting more data and evaluating disease control with our ORR is very important in understanding any type of potential signal. So I think it's, you know, overall promising for the field and in the study of that because what's important is to share our data to advance our all of our products and improve upon them.

Kemp Dolliver (Brookline Capital Markets)

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 what you've seen so far, if any, and take it from there?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Sure. Great question. And I think this is – it 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-177 and 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 sites with managing waste. So we saw that as a barrier. And when we started our SPLASH, we started our slash 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. So we carry the same philosophy forward into actinium and focus on finding or getting access to supply to 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 free actinium and I think continued use of that will pave a pathway forward where we won't need to use any of the actinium, actinium that contains 227. Because again, we think that long half-life of 27 years is going to be very limiting to those clinical sites and managing that waste as headaches that we do not need to add today or tomorrow. Justyna, I'm not sure if you wanted to touch on anything there.

Justyna Kelly, M.Sc. – Chief Operating Officer (POINT Biopharma)

Yeah. Joe, I think you said it very well. I think everyone that we have agreements with are all striving for our 227 free actinium 225 and are continuing along that path.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Okay. Next up, we have Nicole Germino by phone. Your line should be open. Let us know if you can hear us.

Nicole Germino (Truist Securities)

Okay. Great. Thanks for taking my question. Just a quick question on PNT2001 for PSMA, can you talk about the tox that you're seeing versus the salivary tox that you're seeing versus the competitive landscape?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yeah. So, we – so, we have not been in patients yet, so we don't have any experience, human experience with salivary tox. And, of course, in the animal study, it gives you limited experience with what actually manifests there. But 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 on – related to salivary tox in the academic space. I'm not sure who wants to jump on that.

Neil Fleshner, M.D. – Chief Medical Officer, Co-Founder (POINT Biopharma)

Yeah. Yeah. No problem. So, 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 I think our general philosophy is end-of-life patients would probably bear that degree of AE-related toxicity.

However, I think 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. And 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, therefore, and perhaps we could reduce dose or the number of cycles.

Nicole Germino (Truist Securities)

Okay. Great. And just one quick question on the FAP program. Can you talk about you're thinking through the monotherapy versus any potential for a combination strategy and how that timeline looks?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yeah. We can comment on that. I think we have some pre-clinical 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 very exciting. I'll turn it over to Robin for that.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Thanks, Joe, and thanks for the question. We've been doing experiments with – and what we've shared is experiments with our lutetium-labelled PNT6555 with checkpoint inhibitors, in this case, of anti-PD-1 where we 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 with long-term survival when we apply these two together in combination, which really fits the hypothesis that that radiation is a 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 combined together had quite a substantial impact. So I think we're very excited about just speaking sort of mechanistically. I think we're excited about both the potential for combination as well as monotherapy, and we've explored both pre-clinically. Jessica, I don't know if you'd like to add anything.

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Yeah. No, that was very, very complete. It was also a consideration when we were identifying our tumor types how we could evolve our development plans for the potential of combinations as well.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

We'll continue to move along. Thanks, Nicole, for your question. Now, next up, we have Alex Ramsey from William Blair. Your line should be open.

Alexandra Ramsey (William Blair)

Hey, everyone, and thank you so much for holding this session and for taking my question. So, I had another question about actinium and, 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 DOTA particles have in the tumor site.

So, I was just curious given the complicated decay pattern if there's a risk of the free DOTA particles being in the patient's or before it reaches the tumor, either from decay chain, you know, during circulation or even before it's injected or if that risk is largely minimized given the long half-life?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

All right. I'll turn that over to Robin and then probably Justyna to comment.

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Sure. I can comment based on some of it. So, it is a complicated decay, I think, after you have that, the first decay of actinium, that is – it is essentially lost or if it breaks out, it's no longer chelated, which is why we like the internalization.

And – but, as you pointed out, actinium has a relatively long half-life. And so, 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, and that's one of the things that we like about this molecule.

It clears very, very quickly, except for the sites where PSMA is expressed, such as prostate tumor cells, where it's internalized, and then that is retained within the tumor. So, you catch that whole decay but, otherwise, you get a rapid clearance via the kidney into the urine, which is what you'd expect for a molecule like this.

And so, you don't have a persistent circulating molecule that's labeled actinium, and it's – it sticks to the tumor and, otherwise, really flush with rapidly normal systemic tissues and systemic circulation. Justyna, did you want to add anything to that?

Justyna Kelly, M.Sc. – Chief Operating Officer (POINT Biopharma)

No. I think Robin touched on the key part here is that you want to be able to internalize that before that decay happens and you have potential escape of the isotope from the ligands 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. But with the longer half-life and rapid clearance and, of course, internalization, we're looking to mitigate that.

Alexandra Ramsey (William Blair)

Oh, sorry. I have just one other quick one. You mentioned like moving on to other isotopes potentially beyond actinium and lutetium. And I think, in the past, you've mentioned terbium. So, I was just kind of curious if you're still looking at this. And I think you've mentioned that one of the benefits is the auger electrons that are also emitted, so I was just wondering if that's the only benefit and what other assets there are for auger electrons specifically, what clinical data there is that demonstrates the benefit of this type of emission.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Yeah. The data out there on terbium-161 is somewhat limited due to extremely tight supply chain on that. That's driven actually out of what you're irradiating in the reactor, which is gadollinium-160. So, that has limited a lot of human clinical data that's been out there. The preclinical data is interesting and does show that there could be a difference that that auger could bring. But, largely, if you look at everything else, that terbium is very similar to lutetium with the addition of that auger. So, there are some studies and I'll flip it over to Robin here to speak to. So, we continue to explore the opportunities with that isotope as well as others. So we continue to explore the opportunities with isotope as well as others. So, again, we look to fill our toolbox of isotopes as full as we can, evaluate those in discovery and development and then bring forward the ones that we think have – are going to generate compelling clinical data. Terbium again, very interesting, but very, very early on clinically. But maybe Robin , could you speak a little bit to the preclinical data that we're seeing in academia?

Robin Hallett, Ph.D. – Senior Vice President, Discovery and Translational Sciences (POINT Biopharma)

Yeah, I think there's a really nice study that came out of the Paul Scherrer from Cristina Müller's lab that showed that terbium was particularly potent at killing cells when it was attached to ligands that localize in the membrane. These particular studies were done with SSTR2 agonist and antagonist. And you saw really the biggest difference in in sort of killing potential between the lutetium versus terbium when you had ligands that localize on the membrane.

And so I think this is just a small piece of data, hopefully there's much more data that comes forward to help us understand this. But I think it's all about identifying based on the characteristic of your ligand and the characteristics of the patient 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. And so we really want to understand that scientifically and match in a rational way, the right isotope to put on the right ligand for the right patient population.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Thanks. And next up, we will have AJ Velasquez-Mao from Jefferies. Your line should be open here in one second.

AJ Velasquez-Mao (Jefferies)                                                                                                                     

Hi, all AJ 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 timeline to market in 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.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Hey. Yes. We haven't provided direct TAM assessments for PNT2004 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 that. But we're going to learn a lot more in the developments that will likely narrow that down, so an incredible addressable market out of the gates. But I think as we start to read this down and learn more, we're going to see that get narrowed into some more focused indications or more focus combinations and find out where it works and where it doesn't work. So obviously a ton of potential today, but we've got to read that down. So we haven't spoken to that directly.

But you can see that there's potential here in pancreatic cancer, which is an incredible high unmet 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, so that's our focus there, as well as seeing where we can expand that into other areas where combinations may make sense.

On the PNT2001 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-Lu 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 and that as well in the BCR or We have to funnel that down for the patients that will be addressable here and then as well in the BCR or oligometastatic hormone sensitive population. You know, that's quite large, 214,000 patients. Obviously, you're going to add some funneling down there as, you know, certain criteria and we'll learn more in the clinical development whereas it will be well suited to patients and obviously not well suited to patients.

So, again, very large markets. And the BCR oligometastatic space is significantly larger than what we're seeing in the SLASH patient population or anything that's moving into the metastatic space. So, 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.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Okay, thanks. Okay. Next up, we have Hangfei Fu from TD Cowen. Your line should be open.

Hangfei Fu (TD Cowen)

Thank you. This is a really informative session. My question is regarding your recent ask for update with the early activities seen to PSMA therapy with both alpha and beta emitters. I just want to take your – can I get your general insights on...

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

That’s Convergent, on the Convergent poster.

Hangfei Fu (TD Cowen)

And I just kind of see what's the deal like targeting therapy with alpha and beta since your FAP program also have alpha and beta and native programs.

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Sure. So, thanks for the question. Jessica, did you want to take the question on the combinations and or the converging combinations to PSMA?

Jessica Jensen, MPH – Executive Vice President, Clinical Development (POINT Biopharma)

Yeah. I mean, the tandem 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. So this is, you know, a very early data to show primarily in a design that was for safety that Dr. Tagawa presented. And I think that at this point in time, that's really all that can be shared is that there is scientific principle there. And that is what was evaluated in Dr. Tagawa's study.

And then speaking to us, looking at the FAP inhibitor program. So that – is it intended to be a combination. It's tended to be look at lutetium separate from actinium? So right now the lutetium programs in the clinic, the actinium program still sitting preclinically just so we can understand that more and how we deploy it clinically? And so nothing really to comment there from a combination perspective that – that's not our intention in moving forward there at this time.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Hangfei, do you have one more or no? That's it. Okay, let's just go back to the top, there's one or two – let's just one or two more. Jeff Jones, your line should be open again from Oppenheimer.

Jeff Jones (Oppenheimer & Co.)

Great. Thanks, Daniel. You guys mentioned business development. Could you comment on sort of key criteria or what you're looking for in terms of in-licensing?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

Definitely. So we are – as we look at in-licensing, of course, we're looking kind of in two areas. One would be technology to continue to build out our platforms that will drive our discovery programs. So making certain partnerships to develop kind of new novel ligands. And then we're also looking at existing ligands that are out there that have either generated very compelling preclinical data. But we have a real focus on Phase 1 Phase 2 data. So 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. So more clinically, Phase 1, Phase 2 data and preclinically more platform that we can generate more lead ligands from.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

Okay. And then we'll just loop back to Kemp Oliver for one more and then we should be wrapping up here shortly.

Kemp Dolliver (Brookline Capital Markets)

All right. Thank you so much. This is going to be – this is a wide open question. So if you have capital coming in over the next few years, the amount actually 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? And what's – 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 preclinical, where do you think you would put incremental investment capital if you had it available?

Joe McCann, Ph.D. – Chief Executive Officer, Co-Founder (POINT Biopharma)

A 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. So that's both to bring forward redundancy, but to bring forward that internal capacity for new isotopes. So isotopes that we may not have currently in the clinic, but that we may be looking to bring in. So again, build out or bring in host our own supplies of those which we see as being a key aspect of this business is controlling that. So that gives us the ability to deploy it there.

That, of course, then goes hand-in-hand with good clinical data, so. Not to repeat the business development piece, but, again, tying those choices on those isotopes, obviously tied to exciting ligands that allows us to drive a more robust clinical development program. So really that that firm investment in driving those early stage programs forward when we get exciting data to be able to move them quickly forward.

So for example exciting data FAPi, we would be able to just start branching out those trials and being very aggressive in generating Phase 2 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 looking into Europe.

So I think the focuses are ensuring the current supply chain, expanding our internal access to isotope combined with those driving platforms and our discovery programs to bring it 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 1 and Phase 2 programs that we can potentially in license. And then 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.

Daniel Pearlstein – Director, Strategy (POINT Biopharma)

All right, thanks so much. So and that concludes our formal Q&A portion with our covering analysts. We appreciate everyone for taking the time here today and looking forward to continuing the dialogue with all of you. And thanks to all our presenters and analysts who have asked questions. Have a good day and looking forward to speaking with you soon.