76 Under the agreement, Kodiak and Lonza planned a custom-built facility (“Ursus”) dedicated to the commercial-scale manufac f turing of Kodiak’s drug r subs u tance. In January 2023, the custom-built manufact f ur t ing suite Ursus was commissioned as a cGMP facility. Kodiak worked together with Lonza and regulatory r authorities to obtain approval for Ursus, and we released our first commercial scale cGMP batch of tarcocimab in July 2023. In October 2023, Kodiak made a final payment of $26.8 million to Lonza for final activation of Ursus. Separately, tarcocimab a drug r product based on our go-to-market formulation was released in March 2024 and is ready for use in the GLOW2 and DAYBREAK pivotal studi t es. KSI- S 501 Clin l ical Program Updatet KSI-501 is a first-in-class bispecific f molecule designed to inhibit two mechanisms implicated in retinal diseases: vascular endothelial growth factor (“VEGF”) and interleukin-6 (“IL-6”). IL-6 is a pro-inflammatory cytokine and growth factor implicated in the pathophysiology of multiple retinal diseases and, in conditions for which anti-VEGF treatment is used, elevated levels of ocular IL-6 have been associated with poor anti-VEGF treatment response. The bispecific mechanism of action of KSI-501 is designed to provide potent inhibition of (i) VEGF-mediated angiogenesis and vascular permeability through a solubl u e decoy receptor inhibiting the binding of VEGF-A and PLGF to their cognate receptors and (ii) IL-6 mediated inflammation through an antibody that binds solubl u e interleukin-6, inhibiting its binding to both solubl u e and membrane-bound IL-6 receptors. In cell-based assays, KSI-501 inhibited angiogenesis and also normalized inner and outer blood retinal barriers; dual inhibition of VEGF and IL-6 by KSI-501 confer f red supe u rior normalization of cell morphology and junctional biology compared to either anti-VEGF or anti-IL-6 monotherapy. a We believe KSI-501 has the potential to become a new category r of retinal medicines with greater therapeutic effi f cacy than existing therapies. Kodiak intends to develop KSI-501 as two therapeutic programs in parallel, KSI-501 (formerly KSI-501ABC) and KSI- 101 (formerly KSI-501P), to address different unmet needs. KSI- S 501 KSI-501 is an anti-IL-6, VEGF-trap a bispecific antibody biopolymer conjugate built on the ABC platform and is being developed for high prevalence retinal vascular diseases to address the unmet needs of targeting multiple biologies and extended durability. A Phase 1 trial was conducted to evaluate its safety, tolerabi a lity and bioactivity in DME patients. In Februa r ry 2024, the Phase 1 stud t y results were presented at the Angiogenesis, Exudation, and Degeneration 2024 Virtua t l Meeting. Kodiak believes the Phase 1 study t met its objectives: 1) repeated monthly dosing of KSI-501 was safe and well tolerated; 2) KSI-501 demonstrated bioactivity in both functional (vision) and anatomical (OCT CST) measures. Kodiak intends to advance KSI-501 into a Phase 3 study t DAYBREAK in 2024 to evaluate its effi f cacy, durability and safety in wet AMD. The DAYBREAK study t is intended to be a non-inferiority study t evaluating KSI-501 dosed every r 4 to 24 weeks, compared to aflib f ercept dosed per labe a l. The DAYBREAK study t will use an enhanced formulation of KSI-501 educ d ated from tarcocimab’ a s commercial manufact f ur t ing scale-up. We are in the process of obtaining regulatory r feedba d ck on the study t design and intend to initiate the study t as soon as regulatory r alignment is completed, targeting mid-2024. KSI- S 101 KSI-101 is the unconjugated protein portion of KSI-501 and is a novel bispecific protein targeting IL-6 and VEGF. We intend to develop KSI-101 for patients who have retinal fluid and inflammation. Currently there are no availabl a e intravitreal biologic therapies addressing the spectrum of inflammatory conditions of the retina. We believe that retinal inflammatory conditions represent a new market segment separate from the establ a ished anti-VEGF market. KSI-101 is a clinical prospect with opportunities and risks uncoupled from the ABC Platform, and as such is an important part of our late-phase portfolio. We intend to initiate a dose-finding Phase 1b study t in the second quarter of 2024 to evaluate its safety and tolerabi a lity and identify two dose levels to progress into pivotal studi t es. We are currently in the process of obtaining regulatory r feedba d ck on the design of the pivotal program, and we hope to initiate dual Phase 2b/3 studi t es later in 2024. KSI- S 501 and KSI- S 101 manufa u cturing We have been progressing the manufact f ur t ing of KSI-501 and KSI-101 in preparation for the anticipated clinical studi t es. Clinical material for both KSI-501 (50 mg/mL strength in our enhanced formulation) and KSI-101 (100 mg/mL strength) were successful f ly manufactur t ed in the first quarter of 2024.