PDS Biotechnology Corporation Common Stock KOL event

Good morning and welcome to all attending PDS Biotechnology's key opinion leader event this morning. I'm Frank Bedu-Addo, as Tara said, Chief Executive Officer of PDS Biotechnology. I would also like to offer a warm welcome to Dr. Jonathan Hernandez, who is Chief of the Surgical Oncology Section at the National Cancer Institute, and who will be presenting some of the excellent work he has done with his patients and the compelling clinical research that he and his team continue to perform in metastatic colorectal cancer. Before I start, I will quickly walk through today's agenda. Next slide, please. I will provide a quick introduction to PDS0301, which will be the subject of discussion today.

Dr. Kirk Shepard, PDS Biotechnology's Chief Medical Officer, will then address the state of affairs in the treatment of metastatic colorectal cancer, and he will hand over to Dr. Hernandez, who will discuss his ongoing phase II study of PDS0301, a second-line and third-line treatment of metastatic colorectal cancer with liver metastasis. The event will conclude with a summary and question and answer session. Please be aware of the company's forward-looking statements, and ensure that you are fully aware of the risk factors associated with the company as filed with the SEC. Next slide, please. Next slide. Let's begin with the introduction to our proprietary immunocytokine, PDS0301. PDS0301 is an antibody conjugated interleukin 12, or IL-12. IL-12 is a broadly studied and naturally occurring immunological protein or cytokine that is well-documented to be a potent activator of our T cells and natural killer cells.

IL-12 is also documented to have the ability to promote an effective antitumor immune response. Why then has IL-12 not been successfully commercialized as an anticancer therapy? There are a couple of important reasons. First, IL-12 produces significant inflammatory toxicity when in the circulating blood, therefore necessitating a low dose. It also has very low presence in the tumors. Due to these two factors, recombinant IL-12 therefore has a very narrow therapeutic window, which may differ from patient to patient, and these effects have prevented its successful development. Next slide, please. PDS0301 is designed to overcome these specific limitations of IL-12. With PDS0301, two molecules of IL-12 are fused to the antibody called NHS76. This antibody binds to free DNA that is released by dying or damaged cells in the body, which we will find delivers IL-12 into the patient's tumors.

Importantly, the binding holds it within the tumor for an extended period of time, as I will show you in the next slide. Remember, I also said IL-12 is fused to the antibody. This is a unique but very important feature of PDS0301. Unlike traditional antibody-drug conjugates, this fusion is clipping resistant, and therefore does not allow for any free or unconjugated IL-12 to exist in the body. The key takeaway here is that PDS0301 drives IL-12 into the tumors and retains it within the tumors for a prolonged period. In addition, very importantly, any agent that promotes tumor damage or tumor cell death will create ample binding sites for PDS0301, therefore delivering it even more efficiently into the patient's tumor. Next slide, please. Here on this slide, we see pictures from a published study that show the unique characteristics of PDS0301.

In this preclinical study, both PDS0301 and traditional recombinant IL-12 had a fluorescent tag attached to them to allow trafficking and quantification of IL-12 in the tumors. We see the color scale on the right-hand side of the slide, providing a quantitative estimate of the IL-12 in the tumors with time. We see that with PDS0301, within 24 hours, there's already a high concentration of PDS0301 in the tumor, as we can see by the bright red-orange fluorescence in the tumor. By 48 hours, the fluorescence intensity in the tumor has increased even further with PDS0301. Notably, recombinant IL-12 levels never get that high, and PDS0301 remains present in decent quantities even after 72 hours. With this study, the key takeaway is this unique feature. High concentrations of IL-12 in the tumor, and the sustained high concentrations within the tumor over a few days.

This sustained presence, in this case, provided superior ability to change the tumor's biology or immunology to enable a more effective immune attack on the tumor by the T cells and the natural killer cells. Next slide, please. Let's quickly review here how we use tumor damage with PDS0301 to promote an anti-tumor response in the study that we are about to discuss. Chemotherapy, starting with the green, chemotherapy is administered to enhance the initial tumor damage. PDS0301 is then administered by simple subcutaneous injection, just like taking a flu shot. Next, PDS0301 then targets the tumor and binds to the free DNA-histone complexes within the tumor. IL-12 generates significant local inflammation within the tumor and inhibits immune-suppressive cells such as myeloid-derived suppressor cells and regulatory T cells, which are well-documented to block or suppress the anti-tumor immune response. Right? This ability to inhibit the immune-suppressive cells within the tumor is an important feature of PDS0301.

It also causes T cells and natural killer cells to infiltrate into the tumor, where the IL-12 then activates and expands these immune cells. These activated and potent T cells then cause tumor death and expose further binding sites for additional doses of PDS0301. This process continues as tumor shrinkage and patient survival continue. Next slide, please. Here we see a slide from a published preclinical study of MC38 colon cancer that shows this effect I described very clearly. In this study, docetaxel is used to induce the tumor damage and to create the binding sites for PDS0301. The bar chart on the left shows high necrosis induced with docetaxel administration and higher necrosis when combined with PDS0301.

Now, the tumor regression plot on the right-hand side shows that administration of docetaxel on its own does not induce any tumor shrinkage. You see this from the red line. Recombinant IL-12 does not induce any tumor shrinkage either, as you can see from the gray line. When docetaxel is combined with recombinant IL-12, there is again no anti-tumor effect, as we see with the green line, as IL-12 is not designed to recognize the tumor damage. However, when docetaxel is then administered or combined with PDS0301, as we can see from the purple line, all of a sudden, it drives the IL-12 into the tumors and potent anti-tumor activity is seen. As we can see here, actually, PDS0301 is even shown to have some anti-tumor effect in this model, even as a monotherapy, as we can see from the blue line. Next slide, please. With this introduction to PDS0301, you may understand why we are so excited about the potential of this investigational therapy to significantly advance the treatment of several solid tumors.

We have seen promising results in HPV-16 related cancers, in prostate cancer, and also in colorectal cancer. Importantly, as seen on the right, the National Cancer Institute has exposed PDS0301 to almost 400 patients, and it has been well-tolerated without the high toxicities traditionally seen with IL-12, which is, again, very promising for its advancement. With that said, I will hand over to Kirk.

Thank you, Frank. First slide. Let's look at our lead indication now as far as our project with PDS0301 and the challenges and facts about metastatic colorectal cancer. Colorectal cancer ranks third in incidence. That's 10% of all cancer cases, and second in cancer mortality worldwide. That's about 1.9 million new cases and 900,000 deaths in 2022. For some unknown reason, the incidence under age 50 is rising in many countries and is now the number 1 leading cause of cancer deaths in adults under 50, which is why successful treatment of colorectal cancer beyond localized tumors, that is beyond surgery, is now a large unmet need. The second point, about 95% of the metastatic tumors are pMMR and MSS. This is a common description of a molecular biomarker classification used to describe how colorectal cancer tumor handles DNA repair.

Our target population will be pMMR, or proficient mismatch repair, also referred to as MSS, microsatellite stable, in advanced third-line metastatic colorectal cancer. This is the most common molecular subtype of colorectal cancer and represents 95% of colorectal cancer, and it does not respond to immunotherapy. Only 5% of colorectal cancers are dMMR, that's deficient mismatch repair, or MSI-H, microsatellite unstable. These do respond to PD-1 blockades such as pembrolizumab. The third point, when compared to patients without liver metastasis, the presence of liver metastasis in colorectal cancer is a main driver of morbidity and mortality in these patients. Liver metastasis will occur in approximately 50% of patients with metastatic colorectal cancer. The fourth point, objective response rates decline with successive treatment lines.

Here you see the three columns, first line, second line, and third line, and you see that it dramatically decreases as you go through the lines with 53%-65% in first line, second line 11%-20%, and then third line 1%-6%. These values illustrate trial benchmarks, not pooled estimates, and are not meant to be direct comparisons of other therapy, but still give you an idea as far as where the treatment is with this disease. Slide 12. Here you see a few controlled trials in metastatic colorectal cancer, then third and fourth line. Even though cross-trial comparisons are descriptive, they are not head-to-head comparisons, and populations will vary as far as their prior therapy and eligibility. You can see the mean ORR, or the objective response rate, and the median overall survival are not very encouraging.

The mean ORR in the experimental arms is about 2.5%, and the median overall survival is under a year, at 7.9 months. Therefore, again, the successful treatment of third-line metastatic colorectal cancer is a large unmet need. PDS Biotechnology is fortunate to have an esteemed partner from the NCI to work with us with this challenge. Next slide. It is now my pleasure to introduce Dr. Jonathan M. Hernandez, Investigator and Chief of Surgical Oncology Section at the NCI and Center for Cancer Research. Dr. Hernandez graduated from medical school with honors from the University of Florida and completed general surgery training at the University of South Florida. During his residency, Dr. Hernandez spent two years at the Moffitt Cancer Center and Research Institute studying molecular diagnostics for liver metastasis.