TuHURA Biosciences, Inc. Common Stock Study update

Will do. Thank you, Mike, and thanks for hosting this fireside chat today. Before I get started, as is typical with presentations of this type, we will be making forward-looking statements and remind you to look at our SEC filings for more information on the company's development programs and the associated risks. Before I jump into the results, why don't we go ahead two slides, Jack. There you go. All right. Before we talk about the results, I think it is helpful to provide a little background on the different Merkel cell patient subsets. We will talk about the trial design. We will touch on how it relates to our ongoing phase III study. MCC is a very aggressive form of skin cancer. It is unlike melanoma or other forms of skin cancer. About 3,800 new cases diagnosed in the U.S. each year.

About 15% of those 3,800 patients, they will present with local regional disease, and they undergo potentially curative surgical excisions, and then they get adjuvant KEYTRUDA to try to prevent possible recurrence. Then there is about 55% of patients who have advanced cutaneous and superficial nodal disease, Stage III, or metastatic disease, Stage IV, and they receive KEYTRUDA in the frontline standard of care. That is the patient population that we are studying in our ongoing Phase III study. This is the group that we are going to talk about today. 30% of patients, however, have metastatic Stage IV disease when they first see a physician. They have these so-called deep-seated metastatic lesions.

It is this subset of patients that we are enrolling in our Phase I-B, from which we will present kind of a first look at how is IFx working now in the frontline treatment setting of metastatic disease, especially large bulky tumors. You may recall our Phase III randomized placebo-controlled trial of IFx plus KEYTRUDA or KEYTRUDA plus placebo requires patients to have tumors that can be injected with a relatively small needle that is being used in the Phase III study. 30% of the patients that do not present with cutaneous and superficial nodes essentially are not eligible for that Phase III study. To address the potential of how IFx could work in the frontline treatment of these patients, we designed the current Phase I-B, what we call our 2023 trial. We used to call it the Basket trial, but we refer to it internally as our 2023 trial.

We go to the next slide, and we will show you the design of the study. There we go. All right. This trial focuses on patients administering IFx via a weekly times 3 schedule. These patients that are on this study will often have large bulky tumors that are deep in muscle or the abdomen or organs like the liver or lungs, and they require ultrasound or CT-guided methods to administer drugs like IFx-2.0. The design of the study, this is a frontline treatment study like we are doing in the ongoing Phase III study. IFx is given weekly times 3 injections along with KEYTRUDA every 3 weeks per the product label. As I mentioned, this is the first time that we are looking at IFx outside of the existing placebo-controlled trial in the frontline setting. The endpoints are pretty straightforward of a Phase I-B study.

We are looking at both the feasibility of administering IFx this way through ultrasound or CT-guided techniques. Of course, we need to evaluate the safety of administering IFx. We are also going to look at efficacy, and here we are determining the objective tumor response to therapy and duration of response, and we use what is called the RECIST criteria, and this is the universally accepted method for determining tumor responses. This trial provides us, as I mentioned, clinical response data for the first time in a frontline treatment setting, and really can serve as kind of a proxy for potential response rates that we may see in our placebo-controlled Phase III trial, which as I mentioned, is also in a frontline setting.

So if we take a step back, you may recall our experience with IFx in advanced or metastatic Merkel cell was not in the frontline setting, but rather these were patients who had progressed while receiving the standard of care in frontline with a checkpoint inhibitor like KEYTRUDA or avelumab. You may recall 50% of patients who receive frontline therapy with the standard of care KEYTRUDA will progress. They will fail, and when they fail, they have no subsequent approved or effective therapies. We recognize that as really representing a significant unmet medical need, and that was the patient population we initially studied in our prior IFx-2.0 trial. In that study, patients who failed KEYTRUDA or a similar class of drug were enrolled on IFx. They received IFx weekly times three, like we are doing here.

Following IFx, they were rechallenged with KEYTRUDA or again, a drug within the same class, which is called avelumab. IFx in that study was able to salvage 67% or five of eight patients who achieved a major durable anti-tumor response. We saw both complete responses, where there was no evidence of tumor, or partial responses that were lasting on average 23 months, some even as long as 33 months. So that was the data that we took to the FDA to determine what kind of trial design would provide the fastest possible route to potential approval given the unmet medical need in this patient population.

The FDA, specifically the so-called Oncology Center of Excellence, encouraged us to consider their Project FrontRunner initiative given the encouraging results that we were seeing in the Phase I study amongst patients who were failing frontline therapy and being salvaged by IFx when they are rechallenged with drugs like KEYTRUDA. Give you a little background on Project FrontRunner. It is really a significant move for the oncology community. As you know, clinical development of most new cancer therapies are conducted in relapsed or refractory patient populations, just like we did. The clinical investigation of new therapies in the earlier treatment settings may give more patients the opportunity to receive an investigational agent when their disease-related factors do not prevent them from participating, and when the treatment has the potential to alter the course of their disease more effectively.

I mean, essentially, the comment that was made, if you can prevent patients from progressing, would not that be better than trying to salvage them after they failed a therapy? That was the rationale for the design of the currently enrolled rolling Phase III frontline study. With that background for the rationale for the 2023 trial, I want to share some preliminary results of IFx-2.0 for the first time in the frontline treatment of patients with large, bulky, deep-seated Stage 4 metastatic disease. All right, so this is the first patient who was treated at Moffitt Cancer Center. As shown, it was a 78-year-old male. As you will see, had Stage 4 metastatic Merkel cell carcinoma, and the patient's disease was involving the right gluteal intramuscular lesion. You will see he had a lot of lesions deep in the muscle.

Also had disease in the pelvic lymph nodes, in the lung as well. This patient received CT-guided IFx-2.0 in the intramuscular administration weekly times three, and then received a standard dose and schedule of pembro, which is KEYTRUDA, every three weeks. pembro is typically given per the label every three weeks until either you see the patient progress, until the patient may have a pembro-related toxicity, or they reach two years. Importantly, not only was it feasible to administer IFx to this patient, but it was safe. Safe meaning that we didn't see any serious adverse events, so-called SAEs. The encouraging part was that this patient had a confirmed partial response at the week 12 evaluation as well as the week 24 evaluation. The gluteal lesion that was injected with IFx was one of the lesions that was included in the so-called response assessment.

I think it's fair to say that a 60% reduction in tumor size, along with minimal toxicity, is a very good benefit-risk profile. Importantly, it's encouraging, right? This is the first time that we have data in the frontline tumor setting. I'm going to show you what that looked like for this patient with some CAT scans. If you look in the upper left-hand panel where that green arrow is, you see what looks like all those white dots. Those are metastatic deposits deep in that patient's muscle. So those were the lesions that were injected. You can also see on the panel below, if you want to look at a different perspective from the CAT scan, you can see all that whiteness in that Dark area, those are tumors. Those are metastatic deposits. Now, if you go to the right upper panel, this is after week 24, and you can see that essentially 60%, 70% of those are gone.