Oruka Therapeutics, Inc. Common Stock Study result

Please go ahead. Thanks, operator, and good morning, everyone.

During this call, we'll be making forward-looking statements related to our current expectations and plans for the company and our clinical program. These statements represent our views as of this call and are subject to risks and uncertainties, including the possibility that final or longer-term results may differ from the interim data presented today, regulatory feedback regarding our planned clinical trials, and other risks covered in our SEC filings. These forward-looking statements should not be relied upon as representing our views as of any date in the future. Please review the disclaimers in today's presentations and our SEC filings carefully. I'll now hand the call over to our CEO, Lawrence Klein.

Thank you all for joining us this morning as we share interim results from EVERLAST-B, our phase II-B dose-ranging study of ORKA-001 in moderate to severe plaque psoriasis. When we presented data from EVERLAST-A earlier this year, we showed an efficacy profile that we thought could be a major advance for psoriasis treatment. Today, we're very pleased to share that our candidate showed highly similar results in a second independent study while also generating the dose-ranging data needed to support moving this program forward into phase III studies. I'll start with a brief overview and the headline findings. Then our Chief Medical Officer, Joana Goncalves, will walk through the study and the results. I'll come back to discuss what these data mean for 001 and our development plans, and then we'll open it up for questions.

Before getting started, I want to thank the patients, investigators, and study teams who have made this work possible. At Oruka, our mission is to advance the standard of care in psoriatic disease. We think combining very high rates of disease clearance with much less frequent dosing can improve the treatment experience dramatically for patients. Our pipeline is anchored on two co-lead programs targeting IL-23p19 and IL-17AF, mechanisms that we believe will remain the gold standard in psoriatic disease treatment and that are each suited for complementary segments of the patient population. With our IL-23p19 inhibitor, ORKA-001, we envision a regimen with once to twice per year dosing and the potential for rates of response that exceed existing options. We'll share data today from that program that increasingly elucidates this profile.

ORKA-002 is our extended half-life IL-17AF antibody with potential for twice-yearly dosing in psoriasis and psoriatic arthritis and quarterly dosing in hidradenitis suppurativa. 002 is now in phase II in both psoriasis and HS, with the first psoriasis results expected in the first quarter of next year. We are encouraged by the continued success and adoption of the first approved IL-17AF inhibitor, BIMZELX, and believe that a long-acting option in the IL-17 class could be something very new and beneficial for patients. In addition, our pipeline now also includes ORKA-004, an extended half-life TL1A antibody that creates opportunities for combinations with both of our co-lead programs. Following healthy volunteer studies, we plan to initiate our first phase II combination study with 004 sometime next year. Today, the focus will be on EVERLAST-B and the week 16 results from that study with 001.

The headline result for today is that the 600 milligram dose delivered 61% PASI 100 and 86% PASI 90 at week 16. Those results are highly consistent with EVERLAST-A. We now have two studies showing complete skin clearance in more than six out of 10 patients and an extremely high rate of PASI 90 or near clearance with a favorable safety profile consistent with the IL-23p19 class. The body of safety evidence continues to grow, and we have now dosed over 250 subjects and accumulated over 100 patient years of experience with ORKA-001, increasing our confidence in the profile we have observed. EVERLAST-B also gives us the dose-ranging evidence we set out to generate. The 600 milligram dose produced the highest rate of complete clearance, and we plan to advance that dose into phase III in the first half of 2027.

Our vision remains an annual maintenance regimen with a six-monthly option. The next important test of that goal is the week 52 EVERLAST-A readout coming in December. Taken together, we think today's data are a substantial step forward for the program. With that, I will hand it over to Jo to walk through the results.

Thanks, Lawrence. EVERLAST-B is a randomized, placebo-controlled phase II-B study designed to support phase III dose selection and further evaluate ORKA-001 efficacy and safety in moderate to severe plaque psoriasis.

The study was conducted at 36 experienced sites across the U.S., Canada, Germany, and Spain. Fewer than 30% of the sites overlapped with EVERLAST-A. This provides an opportunity to evaluate the same high-dose regimen in a new group of sites with a broader geographic footprint and in the context of a dose-ranging study. As in EVERLAST-A, the eligibility criteria were closely aligned with prior IL-23. Participants were adults with a PASI score of at least 12, at least 10% body surface area involvement, and an IGA score of at least 3. Prior exposure to an IL-23p19 inhibitor was not permitted. These criteria allow us to study a population similar to those enrolled in the clinical development programs for established psoriasis therapies. The study enrolled 187 participants, randomized in an equal ratio across 3 active regimens and placebo.

The high-dose group received 600 milligrams at week 0 and week 4, the same induction regimen evaluated in EVERLAST-A. The middle dose group received 300 milligrams at those same time points, and the low-dose group received 37.5 milligrams at week 0 only. All doses were administered subcutaneously. We deliberately studied a broad range of doses to understand the relationship between dose and clinical response. The primary endpoint was PASI 100 at week 16, which represents completely clear skin. We continue to believe that complete skin clearance is the most meaningful goal for patients and dermatologists, and it is particularly useful in distinguishing the performance of highly effective treatments. Beyond induction, EVERLAST-B will also provide information on durability. Participants who achieve PASI 100 at week 28 are re-randomized equally to annual 600 milligram maintenance or to a group that receives no further dose until disease recurrence.

Participants who have not achieved PASI 100 at week 28 receive 300 milligrams every 6 months. The placebo group then crosses over to active treatment at week 16, with annual maintenance planned as part of the open-label extension. This design allows us to assess how long clearance persists after induction and also allows us to gather additional evidence on annual maintenance dosing, on dosing every 6 months for those who may need more frequent dosing, and on periods without further treatment. Today, we'll focus on the week 16 induction results. Baseline characteristics were broadly balanced across the treatment groups and typical of moderate to severe psoriasis populations.

Disease severity was also comparable to EVERLAST-A, though it is worth noting that the participants in the 600 milligram dose group in EVERLAST-B were on average 9 kilograms or 20 pounds heavier than the comparable group in EVERLAST-A and had a higher incidence of prior biologic use. Seeing similar results in these 2 patient populations increases our confidence that the efficacy results with the high dose are reproducible across different baseline characteristics. Turning to the primary endpoint, the high-dose group achieved the highest rate of complete skin clearance, with 61% of participants reaching PASI 100 at week 16. In the mid-dose group, 44% reached PASI 100, and 43% in the low-dose group, while no participants on placebo reached PASI 100. IGA 0, which also represents completely clear skin, was identical to PASI 100 across the groups, supporting the robustness of the assessments in this study.

For PASI 90, both the high and mid-dose groups achieved response rates in the mid to high 80s, while the low-dose group was 70%. None of the participants in the placebo group reached PASI 90. IGA 0/1 response rates were similar to those for PASI 90 across groups. The high response rates across endpoints observed with the 600 mg dose, together with the consistent results from EVERLAST-A and the safety findings, which I will review shortly, support our plan to take the 600 mg dose forward into phase III. The pattern of response for the 600 mg dose shows remarkable consistency from EVERLAST-A to EVERLAST-B. As you can see in the slide, overlaying the response curves from the two studies, the trajectories track very closely through week 16 for both PASI 100 and PASI 90.