Sana Biotechnology, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Thank you very much, Emily. Thank you everyone for coming today and appreciate H.C. Wainwright giving us the opportunity to present Sana today. As you can imagine, in the discussion, I will be making forward-looking statements, so just advise everyone to reference the company's most recent 10-Q filings. Sana. For those perhaps not as familiar with the company, we have two platforms that we are developing. The first one is for type 1 diabetes, that we will be speaking much more to soon. Certainly an enormous challenge for many patients globally. Approximately 10 million people living with the disease on a global basis. We are developing what we expect and hope to be a one-time treatment, cell therapy treatment for type 1 diabetes, and we are looking to file an IND this year and initiate a phase I/II trial. We have been working very hard on this for many years.

It is an exciting time as we approach that. To note also, we did sign a collaboration with the Mayo Clinic earlier this year, which provided some capital in the form of an equity investment and a great deal of support on the clinical trial side of preparation for SC451. So that has been tremendous. We will talk more about that shortly. Second platform is an in vivo CAR T platform that also holds the potential to be transformative therapeutic platform. In vivo CAR T cells have the potential to eliminate conditioning chemotherapy with comparable efficacy versus an off-the-shelf availability versus ex vivo CAR T. We have our lead program, SG293, a non-Hodgkin's lymphoma, which we expect to be generating first in human data the first half of 2027 with that program. So busy times at Sana. Touch on diabetes briefly. As I stated, an enormous condition, disease affecting many people globally.

What happens with the disease is, as many of you may know, is that there is autoimmune destruction of the insulin-producing pancreatic beta cells. Current care, insulin pumps, continual glucose monitoring are helpful, but there has not been a tremendous amount of innovation in the space. Unfortunately, life expectancy is still a decade shorter than those without the disease. So for patients, caregivers, everyone involved, there is a tremendous desire for innovative and advanced solutions, which is what we are working on. Islet cell transplants provide long-term glucose control, but supply is an issue, and they do require chronic immunosuppression, which is certainly not a light burden for patients either. Stem cell-derived islets provide a scalable supply, which has been another challenge, but similarly require the chronic immunosuppression.

Our hypoimmune platform looks to provide a one-time treatment with long-term normal blood glucose without insulin or immunosuppression, and that is the goal we are pursuing. In order to do that, we have to overcome the allogeneic immune rejection, which has been, as I just mentioned, a limitation in transplant and cellular medicine. We do this, accomplish this by a series of gene edits. The first two block the adaptive immune system, so they disrupt MHC class I and II. Then we knock in the edits to allow overexpression of CD47, which blocks the innate immune system. Essentially, this allows our cells to be implanted without any immunosuppression. This has been widely peer-reviewed in many journals, most notably perhaps New England Journal of Medicine, but certainly plenty of research on the platform that can be accessed.

Now, what we are looking to do with this phase I/II study is to provide clinical validation of the hypoimmune islet cells. We have previously run an IIT study in Uppsala, Sweden with cadaveric-derived stem cells. That was UP421. Those cells were taken from the donor, went through our HIP gene modification with our hypoimmune platform, and transplanted into a T1D patient without immunosuppression. The key measured outcomes from this study were safety, immune evasion, certainly, and cell survival. This has been previously reported, but nevertheless quite impressive with that UP421. All primary and secondary endpoints were met in the study. I won't go through the data here, but really a tremendous result for a first proof of principle. This shows that the islet cells survived and functioned through 14 months. This patient continues, and this is quite impressive to see this data being generated.

Here we see PET/MRI evidence of the graft survival, and this essentially shows the islet cells highlighted on the right surviving at week 42. What do we do now? Now we are looking to take SC451 into the clinic and develop this for the broader T1D population. Importantly, we will be making the hypoimmune islet cells from stem cells with this trial, so differentiating it from the cadaveric donor in the UP421 study. We will look to manufacture the cells at scale and deliver as a one-time therapy. Similarly, via an intramuscular delivery into the patient. We've made significant progress in the last 18 months at turning this into a medicine, and there's a lot of work to be done there.

As I said, the cadaveric transplant and other approaches do work, but to get an iPSC-derived stem cell product to becoming a medicine is going to take quite a lot of work and quite a lot of innovation. Currently, as we look toward filing the IND later this year, we're working on completing non-clinical package, getting manufacturing, and the tech transfer work to the CDMO done. That is in process and have had quite extensive regulatory interaction and, of course, clinical planning, which I did reference earlier, and has been helped and enriched greatly by the collaboration with Mayo Clinic. What do we have to do? Next steps to get this done are to complete the GLP toxicology study, non-clinical testing package, complete the GMP tech transfer and manufacturing, which is a significant step and is taking a lot of effort currently.

File the IND, which again, we're looking to do later this year, in the U.S. and one other geography, then initiate the phase I testing and concurrently make significant progress on commercial-scale manufacturing for the cells. Currently, we have a process that works for the phase I-II study, but we will be looking to increase the scale and efficiency of that process over time. This study will have very clear definitions of success, safety, cell survival, and function. So both the company and many people externally will be looking for indication of early immune evasion. You can see in the graphic below where each of these time points will fall as we follow the trial. Importantly, by day 28, we will be expecting to see evidence of immune evasion and endogenous insulin production within that first month.

This is going to be quite an interesting period as the study kicks off and starts. Then of course, we'll be monitoring patients over the longer term and much longer term, but over the following 3-6 months to look for insulin independence. We believe product fully has the potential to deliver that, and that will be really key, of course, to seeing that success. So that was our T1D platform. We also have a second platform based upon fusosome technology, which is capable of cell-specific in vivo delivery. Our approach is differentiated, we believe, than the competition. We have done a lot of work and spent significant time leveraging insights from nature to be able to deliver various payloads to specific cells without lymphodepletion.

We believe we have a unique approach to this that separates cell targeting from cell activation, and we'll talk more about that. The fusosome vector system allows for delivery and transduction of CD8 positive T cells as well as then the expression via transgene integration and CAR expression in the cell to ultimately provide the desired function of targeted cell killing of either B cells or tumor cells. The platform does, we believe, eliminate the need for conditioning chemotherapy. We believe our approach simplifies manufacturing and overall has the ability to make a better CAR T cell. Also to be noted, because of the integration, it does allow for CAR T cell amplification, which we believe will be quite critical to approaching disease activity. So we made two critical assumptions in developing this program. The first is that cell specificity of delivery is important.

This is something we have spent a good deal of time on to really hone this and refine this in. We expect that this will lower the risk of off-target toxicity and also lower immunogenicity risk, potentially providing for a safer product and a more persistent product. Importantly, also with the ability to redose. Then the third point is that it should improve manufacturability also. The second assumption we made that some other approaches do not make, is that integration into the T cell DNA is important. The CAR T cells typically undergo multi-logarithmic expansion inside the patient in order to clear target cells, which we were just talking to. And integrated DNA replicates with cell division, which the mRNA approaches, of which there are several, does not.

These are the two critical differentiating factors for the Fusosome platform versus other integrating approaches, and also the mRNA non-integrating approaches. We did have earlier versions of this Fusosome platform and went back and spent additional time refining this further to come up with what we believe is an improved platform that increases potency and overall probability of success. We made some changes identified here, perhaps most notably minimizing the CAR surface expression to decrease immunogenicity risk. That has led us to SG293, which we are looking to advance into the clinic in the relative near term. We have SG293 and we also have SG227, both of which we are calling our next generation in vivo CAR-Ts. SG227 is a BCMA-directed CAR-T.

For both of these, as you can see in the graphic on the right, there is a novel fusogen that increases the gene delivery and we believe will help us reduce dose. The second important factor to point out here is that there is an activation factor on the vector to increase CAR T cell expansion and function that is shown by the CD3 on the graphic. Then we also took steps to reduce CAR on the vector particle, again, with the goal of reducing immunogenicity and improving manufacturability. Here we see some of the data generated thus far, in terms of the fusogen and the very high specificity shown in the left-hand column there versus the earlier version, SG299, as well as versus blinded VSV-G fusogen. This is very encouraging and compelling to see this come through with this new and improved version of our CAR-T.