60 Degrees Pharmaceuticals, Inc. Common Stock Study update

Thank you very much. Thanks everyone for dialing into this interesting webinar today. This morning, 60 Degrees Pharma disclosed the outcome of a DSMB interim analysis of its severe babesiosis study in hospitalized patients. The DSMB essentially recommended to complete the study as planned. The good news is that preserves our optimistic timeline for launch of ARAKODA for babesiosis in Q1 2028, assuming everything goes okay with the interactions with FDA next year. It also preserves the near-term catalysts of an additional data disclosure around our Expanded Access Program study in immunosuppressed patients and, of course, the unblinding of the data for the hospital study in January of 2027.

I'll be giving a short presentation that will outline the background to everything I just covered, and then we'll get into a Q&A with our KOLs, and then there'll be a little bit of time at the end of the webinar to address some investor questions. You all know that ticks are nasty bugs that can transmit a variety of different diseases. You may be used to thinking about tick-borne disease in the context of Lyme disease, but the whole variety of other infections and syndromes that ticks can cause, including alpha-gal and babesiosis, and today we'll be discussing babesiosis in some detail. The other thing is, the number of tick bites seems to be increasing. This year, we hit a record level of emergency room visits, so ticks are on everybody's minds.

Broadly, we have a portfolio focused on addressing tick-borne disease with a variety of new products. What we'll be focusing on today is ARAKODA, which is an antimalarial approved for malaria prevention in the U.S. market, and its active ingredient is a molecule called tafenoquine. For most of the presentation, I'll be referring to the research and development of tafenoquine for babesiosis. Babesiosis is transmitted by ticks. There is a cycle in wildlife. Once it gets into your body from a tick bite, it invades and replicates and destroys your red blood cells, accumulating a parasite burden over time. The acute symptoms are a lot like flu and overlap with a variety of other illnesses.

The thing that really characterizes the disease is the red cell destruction, which can lead to anemia, and that it also triggers a persistent fatigue, which can be quite severe in some patients and prolong recovery from illness. 25 years ago, a randomized trial was conducted which established the utility of atovaquone azithromycin as standard of care. One of our experts today, Dr. Peter Krause, was the lead investigator on that study, and will share a little bit more about it. Atovaquone azithromycin was shown to be better tolerated than the prior treatment with equivalent efficacy, and so there'll be a lot of reference, particularly to atovaquone in the discussion today. There are two major unmet needs or populations that we'll be addressing today and that are the focus of two of 60 Degrees Pharma's clinical trials. On the left-hand side, we have severe disease.

These are hospitalized patients, and they have a mortality risk of up to 21% in folks with comorbidities. The unmet medical need there is the desire to have new therapeutics with reduced morbidity that result in faster recovery. Then on the right-hand side, we have relapsing disease in patients who are immunosuppressed. They may have illness that goes on for months or years with a lot of recurring episodes of parasite burden and symptoms. There are drugs to treat relapsing babesiosis, but on an individual regimen basis have a relatively poor cure rate. This slide here captures what we know about relapsing babesiosis from the literature. Each of the horizontal bars represents a case. The purple segments show a course of atovaquone therapy, followed in some cases by treatment-free periods, which are highlighted in yellow. What you'll notice is it's very heterogeneous.

Lots of patients get treated in different ways, and many require multiple rounds of treatment before you get clinical success, and even then, the overall cure rate is about 80% on a total drug-administered basis. We know from doing some analyses of these cases that atovaquone regimens are successful about 30% of the time, and we will be referencing that further in the discussion. We know from the literature that tafenoquine added to background therapy, and what we mean by that is an atovaquone regimen, shows additive activity in animal models. These are relapsing parasitemia curves from a severe disease model of babesiosis. On the left, you can see that all six animals in this study in blue relapsed. That is the blue curve, which looks like the control curve, but delayed.

In the middle, you can see that two animals relapsed following tafenoquine treatment, so it did a little bit better. But it took both drugs combined to flatline the parasitemia curve on that horizontal axis, where you never saw a relapse at all. This supported the further study of tafenoquine and atovaquone combinations in immunosuppressed patients, and Peter and Ed will discuss that in more detail. What I am showing here is a representative case from a series of five immunosuppressed patients who were treated with tafenoquine combined with atovaquone regimens. The graph there essentially shows your about eight months of prior therapy, which all failed until tafenoquine was added. Then you started to see a drop in parasitemia, a recovery from symptoms, and negative PCRs for the first time.

That study involved a loading dose of tafenoquine over three days with weekly tafenoquine administered until recovery, and it did establish that combination therapy with atovaquone was important, and Ed and Peter will elaborate on that in a bit more detail. Apart from those five original cases, there have been a couple of others which I am conveying here. The purple segments here show prior atovaquone therapy. The tafenoquine administered at the end of the treatment course is illustrated as either green or red, depending on the success. And you can see here that six out of seven of these patients were successfully treated with tafenoquine, which is a pretty promising outcome so far. ARAKODA, of course, which I mentioned earlier in this presentation, is the brand name of tafenoquine. It was approved in 2018 by the FDA for malaria prevention.

It became commercially available in 2019, and it has a number of features that make it pretty interesting as a potential babesia drug. The first is it has a well-established safety profile. The second is it is a weekly dose because it has a long half-life, and as a follow-on treatment for babesiosis, that is really useful because now you can give a drug once a week. The other thing it has that is useful is a broad spectrum of action against parasites that target red blood cells. And their malaria has a commonality with babesiosis because it is also a parasite that destroys red cells and has a similar symptom and acute manifestation profile as babesiosis. Now we get into the status of our clinical studies. I mentioned that we have two clinical trials that are actively enrolling patients.

The first is the randomized placebo-controlled study, which we disclosed the interim outcome for this morning. That study has enrolled 30 patients as of the 1st of October, when we did the interim analysis. It involved a comparison of tafenoquine to placebo in patients also receiving atovaquone and azithromycin, and its primary endpoint is the time to sustain clinical recovery. On the right-hand side is our open-label Expanded Access Program study in relapsing immunosuppressed patients. We reported earlier in the year that the first three patients in that study, which is a follow-on from the case series that I mentioned earlier. In that prospective study, three patients were cured. Then we have another two patients that will complete the study by the end of this month, and we should have some results to disclose in early November.

Very briefly, this was the mandate that the DSMB had when they did the interim analysis for the hospital study. We, as the sponsor, are told what to do next. We don't have any insight into the actual statistics that the DSMB reviewed. That potential recommendation is in column 2 of this table. The DSMB could have concluded, based on the data, that we'd already met the endpoint and directed us to terminate the study. They could have said that in order to get enough statistical power to see a successful outcome, eventually, we would need to enroll more patients than we originally intended or to complete the study as originally planned. That is, of course, the advice that we received, complete the study as originally planned. They also said there was no safety signal associated with the data.