IN8bio, Inc.

great thank you everybody um thank you everybody here who are here in washington dc for the asgct conference it's exciting to be in person again and everybody online on the webcast we're glad that you could attend today my name is william ho i am the president and co-founder of innate bio we are one of the leading companies focused on the development of gamma delta t cells and it's a really exciting time um very quickly Very quickly, I want to make some introductions to some of the team members that are here today. Myself, I've been in biotech for over 20 years across most areas of the business, but we're really happy to have Dr. Larry Lam, our scientific co-founder, really one of the world's best experts in the translational research around gamma delta T cells. He's been working in cell therapy and manufacturing for almost 30 years. We have Pat McCall, our chief financial officer, who will be with us today. He is a CPA by training, joined us from Turnstone Biologics. And Trishna Goswami, our chief medical officer, hematologist, oncologist by training in her early years after her training. And her practice, she was at Metimmune, AstraZeneca, working on many of the checkpoint inhibitors, and most recently joined us from Gilead, where she joined from Immunomedics. She was actually involved in the approval of Chodolvi in bladder cancer and in triple negative breast. And finally, Kate Rocklin on our team is our chief operating officer, an entrepreneur and actually really well trained in oncology, was trained at Weill Cornell, did much of that training at Memorial Sloan Kettering and really fantastic in making sure everything moves forward for us. Today, we're happy to have two guests as well who will speak. Dieter Kablitz joins us from the University of Kiel. Both of these individuals are widely recognized world leaders in their area. Dieter is an expert in gamma delta T cells. And Bruce Levine from the University of Pennsylvania. One of the earliest CAR-T programs. Dr. Levine has pioneered much of the manufacturing. And today is also the president of the ISCT. So we're glad to have him with us today. So, a quick disclaimer. I want to start off with a video. This video is actually quite exciting. This was created by our scientists and Dr. Lam in the labs. And what you're seeing are brain tumor cells expressing green fluorescent protein. The little white dots are actually gamma delta T cells. And what we're showing here is actually a single gamma delta T cell who's going from tumor cell to tumor cell driving cytotoxicity, killing those tumor cells, and demonstrating serial killing. This is one of the first videos that we're aware of showing that gamma delta T cells can kill multiple targets and continue killing. This video, I'd like to say, actually took us about 30 years. Dr. Lam has spent 30 years trying to improve and perfect the technology as we move forward into manufacturing in the clinic. We're often asked, what are these weird cells? How come there hasn't been a focus on it? So today I wanted to take us all back into time. In reality, the Gamma Delta T cells have been actually for quite a number of years, and in fact, included some of the luminaries in the field. The Gamma Delta TCR was actually first identified by Adrian Hayday, who's at the King's College in London. He identified one of the T-cell receptors. And very shortly thereafter, Sue Dillon, who runs a company today in Philadelphia called Arno, and who was previously the head of immunology at Janssen, described these lymphocytes that were found in the gut of mice. But very quickly, some of the luminaries in the IO space, Malcolm Brenner, Jim Allison, David Raleigh, Mark Davies at Stanford and his partner Chen, identified the other receptor. But you can see a lot of progress was made from 1985 through to the mid-1990s. Our journey actually started in 1992. At that point, a young postdoc was conducting research at the University of South Carolina and was actually manufacturing grass for patients who were being treated for their leukemia. Through the fall of 1992, they were actually treating six pediatric girls. And on Christmas Day, he found himself inside the stairwell of a hospital in tears because the fourth girl had just passed. And it was that experience that drove him to search for what made the difference for those patients. Those patients who lived longer versus those patients who were dying following their transplant. And as you can see here, in 1996, Dr. Lam published the first demonstration that higher levels of gamma delta T cells seem to be associated with better survival. Years later, we had this data. Published in 2007, Dr. Lam is now recognized as having demonstrated that higher levels of gamma delta T cells are associated with survival outcomes. Many of the gamma delta T cell players use this particular Kaplan-Meier curve. You can see those patients that have higher levels have a 71% survival versus those that are low or normal are closer to 20%. Published in 2007, you can see there was a long period of time when there was really nothing in the gamma delta T cell from the mid-90s to the 2005. But right thereafter, we started to see an acceleration of interest in gamma delta T cells. In 2010, the FDA approved the first prostate cancer vaccine, Provenge, and there was a sudden interest in cellular therapy. In early 2011, in the Gamma Delta T cell space, actually, innate pharma published the first study using Gamma Delta T cells expanded in vivo in combination with Rituxan, the CD20 targeting antibody, and found complete responses. Unfortunately, shortly thereafter, we had the checkpoints, Yervoy and Abivo come out, and the company made the decision to shelve their cell therapies as Dendreon unfortunately went bankrupt. Right around the corner was the University of Pennsylvania doing a seminal deal with Novartis to advance the CD19 car and we know the interest that that's driven. The formation of Kite and Juno and the approval of the first CAR-Ts targeting CD19. It's very recently that Dr. Levine and the team at University of Pennsylvania celebrated an anniversary with Emily Whitehead, I believe now being over 10 years out and still in remission. But shortly thereafter, we had the first formation of Gamma Delta T cell companies. We had TC Biopharm, Adacet, and ourselves all formed around 2015. We had Gilead first get into the space with Kite, and then there was an acceleration. In 2018, Fate entered into the space with the first IPS-derived IND approval, but then we saw the pharma coming in with Takeda acquiring two companies, Gamma Delta Therapeutics and Adaptate. We saw Century announce their IPS programs, and we saw the Bristol-Myers. All of a sudden, this is where we are today. with over two dozen companies focused on the Gamma Delta T cells. As a prior investor, I always said that it's very lonely early on, but you know you're doing the right thing and you're in the right direction when all of a sudden people are coming towards you, you're building interest, in the area that you're studying or that you're investing in. And we can see all the companies today working on gamma delta T cells, we have V delta ones, we have TCRs, we have CAR Ts, we have our own drug resistant immunotherapy program, and we have IPSCs. But throughout all of this, we believe that innate bio is a leader in the space. Our team, Dr. Lam, has created some of the seminal contributions to the translational research in gamma delta T cells. We've had a number of firsts. The first to enter the clinic with a genetically modified gamma delta T cell program. The first to deliver a large bolus here in the U.S. of allogeneically delivered gamma delta T cells. and now we're one of the first to create an IPS cell program, and in particular, one that's demonstrated an ability to create both V Delta 1s and V Delta 2s out of IPSCs. We're excited about our knowledge and our know-how and the platform, and I'm really happy to have all of you joining us today and to introduce you to our team to talk about what we've accomplished and what we have right around the corner. And so with that, I'd like to introduce Dr. Lam to the stage and tell you about our very new IPSC program that was introduced here at the ASGCT conference. Larry?

Okay, so... Okay, so I just wanted to take you through this new IPSC program. First of all, just a little review of what is an IPSC. It's a cell that you can take from the skin or from the blood of the donor, and then using four factors called the aminocle factors, the cell can be taken back. At that point, it's a different. specific and self-specific. Following that, you can actually select the forms that express the genes that form the cell medicine. in a large variety of patients. So, this slide, like the previous one, it shows our work with a bio. Again, we take the purple blood cells, they're reprogrammed, and they're taken back into chloropotency, but we, are able to drive both Delta 1 and Delta 2 gamma delta T cells. The first time this has been done. These cells, again, are available for disease-specific edits. They give us the opportunity to custom edit one cell or another cell and possibly even use both cells in a single treatment. of a selected cancer. Again, colon was selected, expanded, and characterized. And we'll share a little bit of data on the next slide. We were able to obtain dozens of individual iPSC followings, including both Delta-1 and Delta-2. The identity of the rearranged TCR is confirmed with sequencing, and we were also able to show the cones were at a normal keratotype And if you look at, to your lower right, you'll see that there's both the Delta-1 and the Delta-2 cells that are showing expressions of pluripotent markers, POC 3-4 and SSA-4. And as they begin their differentiation process in the middle, full cytometry plot, you're seeing expression of CD7 and CD3, both T cell markers. uh both t-cell markers that confirm that we're working with gamma delta t cells but the most important thing is that all three of the clones that were derived are all killing uh a a cancer line this in particular is the u87 uh glioblastoma cell line and they and they almost overlap each other showing the reproducibility of the cell process But importantly also, at a five to one ratio, which is a very low effector to target ratio, they're killing well over 60% of their target, approaching 70% of their target. But that's not everything. We're also able to transduce V-delta-1 cells with our chlorotoxin CAR, which we'll hear a little bit about towards the end of this meeting. And I wanted to emphasize that we've had a V-delta-2 program from the beginning, but this is the first time we've been able to move into delta-1 cells, show that we can transduce these cells with high efficiency with a functional CAR, and then ultimately differentiate them into V-delta-1. into a therapeutic cell product. And this is a little video that shows these IPSC, again, binding and killing these green fluorescent protein-tagged U87 glioblastoma cells. And as you can see, several of the cells sticking to the glioblastoma, and ultimately you see them kind of blubbing up and ultimately clearing the plate. I don't. At this point, I'd like to introduce Dr. Kablitz.

I think my microphone works, I think. Okay, thank you, Dr. Lampe, and thank you for giving me the opportunity to spend a few words on gamma-delta T cells. As Dr. Hu was introducing me, I've been working with gamma-delta T cells maybe for too many years, since the early 90s, so our focus has been on the characterization of the anti-cancer activity of gamma-delta T cells and the mechanisms how these cells are activated. So I would like to convince you why gamma delta T cells are important and from our and many other people point of view are the best effector cells to be used in cellular immunotherapy. And this is just to remind you that there are several types of cytotoxic cells available in the immune system. So gamma delta T cells are just one of several cells which can kill tumor cells. And in addition to the gamma delta T cells, you have the natural killer cells which are part of the innate immune system.