TuHURA Biosciences, Inc. Common Stock Canaccord Genuity's 46th Annual Growth Conference

Jim? Thanks. Good afternoon. Before we get started, as typical with presentations of this variety, we will be making forward-looking statements, and we refer you to our SEC filings for more information on the company.

We are a phase III immuno-oncology company. We have three distinct technologies and therapeutics, and we're focused in two strategic areas: primary resistance and acquired resistance to cancer immunotherapies. Just by way of a summary, we have a phase III trial that's ongoing, accelerated approval, frontline Merkel cell carcinoma. I'll walk you through that, both the technology and where we are from the status. We expect to complete enrollment in the second half of next year and top-line data about the end of the year, early 2028. We'll show you the trial design that we worked out with the Oncology Center of Excellence. We do not need a confirmatory trial.

This has embedded a key secondary endpoint that would satisfy that requirement. Just to manage the risk of all of the changes at the FDA, we have a Special Protocol Assessment agreement with the agency for that study. Our second asset is a VISTA inhibiting antibody. We're the only company that is focusing that type of therapeutic in so-called molecularly defined subsets of AML. We're about to put that into a phase I-B/II study. Craig Tendler, who's one of our board members, Craig ran Global IO for Johnson & Johnson for 25 years. He brought bleximenib into clinical practice, clinical development before he left. So Craig is taking on the leadership for moving that program through his phase I/II effort. We'll close it out briefly talking about a really novel class of antibody-drug conjugates.

We're going to have proof of concept in the first set of animal models later this year. But we are the only immune targeting antibody-drug conjugate in pre-clinical development. We have a couple of meetings that we're presenting at in the second half of the year. Lastly, our largest shareholder stepped up for us, provided us with a $50 million credit facility. This is interest only. It's a five-year term. I'll go through a little bit more of detail, but clearly for us, a very non-dilutive source of operating capital from somebody that owns 18% of the company. Obviously, his interest is not to be diluted, but playing the equity play in the company in terms of the true value as this portfolio moves towards approval.

With regards to some upcoming milestones, as I mentioned, the phase III top-line result is late next year, early 2028. We are going to talk a little bit about at ESMO mini-conference on some of the preliminary results. It is not really a basket trial. This is in the first-line treatment of patients with deep-seated tumors, so we are doing an IR-guided trial for IFx, first-line Merkel cell carcinoma plus pembro. They would not be eligible for the inclusion criteria for the phase III. I mentioned starting the mutated NPM1 mutated AML study. We should start that. We should get FDA clearance next month, and then start the trial shortly after that. Lastly, we will have our first proof of concept data. We should have some pretty interesting data. I am pretty sure ASH will take a number of the abstracts that we submitted this year.

All right, let me tell you a little bit about Merkel cell carcinoma. Not a lot of people know about this skin malignancy, if you will. It is unlike basal cell, unlike melanoma. This is not a, quote-unquote, "immunologic or immunogenic tumor." It is a very aggressive polyoma viral-driven tumor, so it is a viral oncogene. About actually 3,900 new cases a year, 25% of those patients will present with local disease that are treated with curative intent and given checkpoint inhibitors. But 75% of these patients will present with advanced metastatic disease, KEYTRUDA and/or avelumab as the frontline standard of care. Importantly, half of these patients will not respond. If they do not respond, there is no alternative therapies. That is the addressable unmet medical need population that we went after, and I will show you some of that data, why we think it could be successful in a clinical study.

We are going to try to increase the response rate to KEYTRUDA in the first-line treatment of patients with advanced or metastatic Merkel cell carcinoma. Even though it is only 3,000 patients in an addressable target population, it would become the new standard of care if this trial is successful. We think that even though it is a relatively small number, i.e., an orphan indication, it could still be commercially attractive given the fact that you will replace the current standard of care with a new standard of care. All right. Let me tell you how IFx, this technology works. How do you overcome primary resistance? The basis by which tumors, 80% of tumors do not respond to checkpoint inhibitors is that you do not have an activated immune response against the tumor. If you do not have activated T cells, you do not have activated checkpoints to inhibit.

There is no checkpoint to release T cells to become amplified and proliferate and have anti-tumor activity. The whole industry has been searching for how do you make a tumor look foreign to your immune system. You need to have a specific immune response against the tumor. There has been a lot of approaches of activating immune responses that are systemic. They do not really work, right? What IFx does is it takes a plasmid DNA that encodes for a bacterial protein. You inject it in a tumor, and that bacterial protein is transported to the surface of the tumor cell. Now the tumor cell has a bacterial protein which has a very specific pattern, molecular pattern or motif. Your innate immune system has cells that have evolved alongside of pathogens, right? It is your first line of defense when you are born until you start having exposure to foreign antigens.

In this case, this is a strep protein. TLR4 on your innate immune cells will recognize that as being foreign, and it will engulf, i.e. phagocytize, the entire tumor cell, thinking it is a bacterial protein. What you have done now is you have packaged all of the foreign proteins that are in that tumor, and it is now being presented to newly formed T cells and B cells. You activated an adaptive response with activated tumor-specific T cells and tumor-specific B cells. We know that because in our clinical studies, these patients will make antibodies that recognize the viral oncoproteins and a whole slew, a whole host of other neoepitopes that previously they did not recognize. Then, of course, you will see the data that they will respond to checkpoint inhibitors that they previously failed. This was the basis for the discussion with the FDA.

I am just going to go through it briefly. It was a two-stage trial design. It was Merkel cell and squamous cell. We are going to focus on the Merkel cell just because that is where most of the data was generated. IFx is given weekly times 1, 2, or 3 weeks. We wanted to see if we had an escalation in the immune response by more repetitive dosing. It is given into skin lesions or nodal lesions or subdermal, not deep lesions, because it is a tuberculin syringe, you cannot have access to it. 23 patients enrolled, 13 had Merkel cell. We will show you how that worked out in terms of responses. Each of the patients with Merkel cell on this slide came in with primary disease, advanced metastatic, were checkpoint inhibitor naive. They received either avelumab or pembrolizumab, right?

Either a PD-1 or L-1 inhibitor, and they failed it, meaning they progressed with the first time given a checkpoint inhibitor. That is the PD. They came off the checkpoint inhibitor, and they received IFx in up to 3 lesions weekly times 1, 2, or 3 in each of the cohorts. 28-day observation period. Then they went back on the same class of checkpoint inhibitor without IFx, and you can see the responses that were demonstrated here. The first patient had a CR that lasted 23 months. Second patient, I am going to show you that, had a pathologic CR and a PR that was out 33 months. You can see the duration. Some of these were ongoing at the time of the study cutoff for the data. There were 3 patients who did not respond.

I could tell you antibody-wise, they did not recognize some of the epitopes that the other patients that had antibody generation, i.e., they may not have expressed effectively the protein. It is kind of cool translational work, but what is really cool is the fact these patients are having meaningful, durable clinical responses. This patient in the left panel, this patient got 3 months of KEYTRUDA, pembrolizumab, developed that large lesion where the blue arrow is in the thigh. That lesion was injected with IFx weekly times 2. This was dose level 2. Patient was put back on KEYTRUDA, and you can see that large lesion cavitated. It is about an 80% reduction, was classified radiologically as a PR. It stayed that size for a few months. They excised it, and it was reclassified as a pathologic CR, which was ongoing at the time the data cut off at 23 months.

Second patient, we are just showing you when people talk about abscopal-like effects. This patient, again, had 2 months of KEYTRUDA. By definition, primary resistance is failure to have a response within 6 months of exposure to a checkpoint inhibitor. So within 2 months, progressed rapidly, developed these very large, bulky lesions in the abdomen. Those are the blue lines. They had some subdermal lesions that were accessible, so they got injected with IFx times 2, was rechallenged with the same class of checkpoint inhibitor, and again, had about an 80% reduction in the so-called reference lesions, PR, and that was ongoing at 19 months. We took this to the FDA, and we are in the same division that cell and gene therapy, Replimune, and the rest are in. But we asked the FDA if we can bring in somebody from the Oncology Center of Excellence.