Pyxis Oncology, Inc. Common Stock Study update

Please go ahead. Good morning, and thanks for joining us today for our clinical update on MICVO.

My name is Tom Civik, and I am the CEO here at Pyxis Oncology. I am so pleased to be here representing the extraordinary team at Pyxis Oncology. Before we begin, I want to share my deep thanks for the patients who put their trust in us, investigators who helped shape this program, and a long list of partners who have supported and encouraged us through this important journey to unlock the potential of MICVO. As you saw in the press release that went out this morning, we are thrilled to share with you the updated data from our phase I study evaluating MICVO in second line and beyond head and neck squamous cell carcinoma.

Please note that today's presentation includes forward-looking statements, and we encourage you to review the related disclosures, which are available on our website. Joining me today on the call from Pyxis Oncology are Marsha, who heads up our Translational Medicine and Research group, Tom, who heads up our Strategy and Finance, Brian, our Chief Program Officer, and Hongwei, who heads up our Clinical Development team. I am also very pleased to have Dr. Alan Ho from Memorial Sloan Kettering Cancer Center joining us today. Dr. Ho is Chief of the Head and Neck Oncology Service and an Attending Medical Oncologist specializing in the treatment of head and neck cancers. He is also a translational clinical researcher focused on developing innovative and personalized therapies for patients with head and neck malignancies.

Today, Dr. Ho will present the clinical data from our phase I study of MICVO in second line and beyond in head and neck squamous cell carcinoma. He will also join us at the end to answer your questions. Okay, let's get started. I am extraordinarily excited to report that based on the data you will see today, we believe MICVO is uniquely positioned to become a meaningful treatment option for patients with cancer. Let me walk you through the agenda for today. First, the program. MICVO is a first-in-concept ADC with a novel ADC target in the tumor extracellular matrix. Second, the need, and it is significant.

There is a large number of patients in the second line and beyond. With the expected changes in the first line, there will be inadequate options for these patients. Finally, a considerable market opportunity with a total addressable market of over $4 billion in the U.S. Third, the study. Our team built and executed an innovative global study that allowed us to evaluate MICVO either after the current standard of care or after what seems likely to become the future standard of care. The study also evaluated key patient subgroups, including HPV status. Next, the results you will see presented from Dr. Ho show that MICVO as a monotherapy with a 5.4 mg per kg dose cap demonstrates substantial efficacy improvement with a safety profile that is consistent with other approved auristatin ADCs.

Finally, we will review our path forward toward potential phase III initiation in mid-2027. I am also very pleased to report now that we have accomplished our first goal of clearly showing that we have an active therapy and a manageable safety profile in a hard-to-treat cancer. We are actively thinking about where else MICVO could deliver benefit for patients beyond head and neck. With that, let me turn over the presentation to Marsha to walk through the scientific rationale behind MICVO.

Hello, my name is Marsha Crochiere. I am Head of Translational Medicine and Research at Pyxis. I am happy to describe our first in concept antibody-drug conjugate, micvotabart pelidotin or MICVO, to present its novel extracellular matrix targeting mechanism of action and review why head and neck was an ideal cancer for MICVO to pursue first. MICVO is the first ADC targeting a protein in the tumor extracellular matrix rather than on a cell surface like conventional ADCs. MICVO's target is extra domain B of fibronectin or EDB-FN, a non-cell associated splice variant of fibronectin localized predominantly in the tumor ECM with little to no expression in normal tissues and has been shown to be associated with tumor growth, angiogenesis, and metastasis. MICVO is an intentionally designed ADC construct that offers several key potential advantages over conventional ADCs that bind to cell surface target antigens.

The rendering of the construct is on the left. It is a fully human IgG1 monoclonal antibody that has been purposely designed with four key potential advantages. The first is that it is purpose-built. It uniquely targets EDB-FN in the tumor ECM and is engineered for structural integrity with high avidity-driven binding and has site-specific extracellular protease cleavable valine-citrulline linkers. The second is that the ADC is predictable. It has a uniform drug-to-antibody ratio of 4, which provides an improved therapeutic window via conjugation with the engineered cysteine, improve the ADC's stability, and result in reduced free payload detected in serum with a Cmax of approximately 4 days after administration. The ADC is potent. It has four optimized cytotoxic auristatin E microtubule polymerization inhibiting payloads, which have the potential to maximize tumor killing and biological potency in multiple solid tumor types. Finally, the ADC is designed for permeability.

The auristatin E payload has been optimized for membrane diffusion to enable efficient bystander killing as it is released from dying cells, as well as for fast clearance to reduce off-target effects, resulting in better tolerability compared to other auristatins. Collectively, these optimized features for this novel target, along with the three-pronged MOA, which I will tell you about next, differentiate MICVO from conventional cell-surface targeting ADCs. By utilizing the non-cellular targeting mechanism, MICVO offers a novel pioneering approach to deliver anti-cancer activity through a three-pronged MOA. In the first prong, MICVO binds to EDBFN in the tumor ECM, where extracellular proteases active at the low pH cleave the linker to release the payload, which diffuses into nearby proliferating cancer cells and kills them directly.

In the second prong, dying cancer cells release the free payload, which diffuses into nearby cancer cells to promote additional cancer cell killing via the bystander effect, thus initiating a cascade of cancer cell killing throughout the tumor. Finally, in the third prong, MICVO induces an immunosupprimalatory effect where dying cancer cells also release neoantigens, which stimulate immune cell infiltration and elicit immunogenic cell death. Together with its purpose-built design and these three mechanisms, MICVO is differentiated to have the potential to maximize tumor killing and biological potency compared to conventional cell surface targeting and internalizing ADCs. Head and neck squamous cell carcinoma, or HNSCC, is a difficult to treat cancer. Pyxis has identified it as a tumor type that is sensitive to MICVO based on several lines of evidence.

Non-clinical and preclinical analyses have shown that the tumor microenvironment has features such as robust EDBFN target expression, immune inflammation, and mature stroma with straight angular ECM fibers that are conducive for responding to MICVO. Data from preclinical studies show broad anti-tumor activity across multiple HNSCC patient-derived xenograft models with gene expression signatures indicative of proteins involved in linker cleavage and ECM remodeling. Data from an immune refractory HNSCC syngeneic mouse model showed MICVO promoted a more favorable immune microenvironment important for anti-cancer activity and a synergistic effect with anti-PD-1 therapies. Lastly, clinical signals observed in both the MICVO monotherapy dose escalation and combination with pembrolizumab studies showed HNSCC to be responsive to MICVO regardless of HPV status or prior therapies.

These features are not unique to HNSCC and have also been observed in multiple types of solid tumors, suggesting the broad potential for MICVO to benefit patients with other cancer types. Before I turn it over to Tom to discuss the head and neck unmet need, I want to say how proud I am to be working on this truly novel program with broad potential to help a significant number of patients with cancer.

Tom? Thanks, Marsha. I am Tom Dorney, and I head up strategy at Pyxis Oncology.