Summary of Oruka Therapeutics FY Conference Call Company Overview - **Company**: Oruka Therapeutics (NasdaqGM:ORKA) - **Focus**: Advancing the standard of care in psoriatic diseases, including plaque psoriasis and psoriatic arthritis, as well as associated inflammatory conditions like hidradenitis suppurativa (HS) [2][3] Core Programs - **Pipeline**: Two co-lead programs, Orka One and Orka Two, which are extended half-life monoclonal antibodies targeting IL23P19 and IL17AF [2][3] - **Market Potential**: Psoriatic disease market is approximately $30 billion and growing, with a track record of rewarding biologic innovation [5] Clinical Development - **Phase One Data**: Recently read out phase one data for ORKA-002, with plans to initiate two phase two studies in plaque psoriasis and HS [3][4] - **EVERLAST Program**: Two parallel phase two studies (EVERLAST A and B) for ORKA-001 in plaque psoriasis, with data expected in the second half of 2026 [4][13] - **Dosing Strategy**: Potential for once-yearly dosing with Orka One and twice-yearly dosing with Orka Two, aiming for off-treatment remission [4][11][22] Efficacy and Differentiation - **Efficacy Evidence**: Higher exposures of IL-23 antibodies may lead to higher rates of skin clearance, with a goal of achieving PASI 100 (fully clear skin) as a primary endpoint [14][18] - **Unique Profile**: Orka One has a half-life of about 100 days, compared to 28 days for risankizumab, which may enable annual dosing [11][12] - **Combination Strategy**: Plans for a sequential combination of Orka Two and Orka One (Orka 21) to leverage the strengths of both IL-17 and IL-23 profiles [9][27] Market Comparison - **Competitors**: Comparison with existing products like Skyrizi and Bimzelix, highlighting the potential for Oruka's products to offer improved dosing intervals and efficacy [5][6][23] - **Oral Medications**: Oruka believes that biologics will remain the preferred treatment for moderate to severe disease over oral medications, which have not reached similar efficacy levels [33][34] Financial Position - **Funding**: Over $500 million in cash disclosed, providing a strong financial position to support ongoing and future studies [28] Regulatory Considerations - **FDA Engagement**: The innovative design of the EVERLAST trial and the potential for a once-yearly dosing regimen are being discussed with the FDA [35][36] - **Pricing Strategy**: Plans for flexible pricing arrangements based on real-world dosing outcomes, aiming to provide value-based care [40][41] Conclusion - **Outlook for 2026**: Anticipation of significant developments in clinical data and potential market entry, with a strong conviction in the company's innovative pipeline and commercialization strategy [29][44]

Core Insights - Oruka Therapeutics announced positive interim data from its Phase 1 trial of ORKA-002, indicating a half-life of 75-80 days, which supports potential dosing of twice a year for psoriasis and quarterly for hidradenitis suppurativa [1][6] - Phase 2 studies for ORKA-002 are expected to begin in the first half of 2026 for psoriasis and the second half of 2026 for hidradenitis suppurativa [1][4] - The first patients were dosed in the EVERLAST-B Phase 2b trial of ORKA-001 in December 2025, with data anticipated in 2027 [1][5] ORKA-002 Phase 1 Trial Findings - The Phase 1 trial was a randomized, double-blind, placebo-controlled study involving 24 healthy adult participants across three dosing cohorts: 160 mg, 320 mg, and 640 mg [3] - ORKA-002 demonstrated a half-life greater than three times that of bimekizumab, with a comparable Cmax at equivalent doses [6] - The safety profile of ORKA-002 was favorable, with no severe treatment-emergent adverse events reported [6] ORKA-002 Phase 2 Trials - ORCA-SURGE, a Phase 2 trial for ORKA-002 in moderate-to-severe psoriasis patients, is expected to start in the first half of 2026, aiming to enroll approximately 160 patients [6] - The primary endpoint for ORCA-SURGE will be PASI 100 at Week 16, with maintenance dosing evaluating the potential for twice-yearly administration [6] ORKA-001 Updates - The EVERLAST-B trial is evaluating three induction dose levels of ORKA-001, with data expected in 2027 [5][7] - The study design includes re-randomization for patients achieving PASI 100 at Week 28, testing the potential for yearly dosing and extended off-treatment remissions [7] Company Overview - Oruka Therapeutics is focused on developing novel biologics aimed at setting a new standard for chronic skin disease treatment, particularly plaque psoriasis [8] - The company's mission is to provide high rates of complete disease clearance with infrequent dosing, potentially as little as once or twice a year [8]

© 2 0 2 6 O R U K A T H E R A P E U T I C S Disclaimers The information contained in this presentation has been prepared by Oruka Therapeutics, Inc. (the "Company") and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subject to change without notice, and is based on publicly available information, internally developed data as well as third party information from other sources; (b) does no ...

Core Viewpoint - Oruka Therapeutics is set to present at the 44th Annual J.P. Morgan Healthcare Conference, highlighting its focus on developing novel biologics for chronic skin diseases, particularly plaque psoriasis [1]. Company Overview - Oruka Therapeutics is a clinical stage biotechnology company dedicated to creating innovative biologics aimed at establishing a new standard for treating chronic skin diseases [2]. - The company's mission is to provide patients with chronic skin diseases, such as plaque psoriasis, the highest possible freedom from their condition, targeting high rates of complete disease clearance with infrequent dosing, potentially once or twice a year [2]. - Oruka is advancing a proprietary portfolio of potentially best-in-class antibodies engineered by Paragon Therapeutics, which target the core mechanisms underlying plaque psoriasis and other dermatologic and inflammatory diseases [2].

Company Overview - Oruka Therapeutics, Inc. (ORKA) is an early-stage immunology company focused on developing therapies for psoriasis and related diseases [1] - The company's pipeline includes biologics ORKA-001 for plaque psoriasis (PsO) and ORKA-002 for PsO, psoriatic arthritis (PsA), and hidradenitis suppurativa (HS) [1] Product Pipeline - ORKA-001 and ORKA-002 are designed to have improved efficiency in treating their respective conditions [1]

Core Insights - Oruka Therapeutics has received mixed ratings from analysts, with Guggenheim initiating coverage with a "buy" rating and a target price of $60.00, while HC Wainwright lowered their target from $45.00 to $40.00, maintaining a "buy" rating [1] - The average target price for Oruka Therapeutics is $48.88, with one analyst rating it as a Strong Buy, seven as Buy, and one as Sell [1] - The company's stock has shown a recent increase of 4.1%, with a market cap of $1.47 billion and a P/E ratio of -15.95 [2] Financial Performance - Oruka Therapeutics reported earnings per share of ($0.55) for the last quarter, slightly beating analysts' expectations of ($0.56) [3] - Analysts project an earnings per share of -$3.41 for the current fiscal year [3] Insider Activity - Insider Joana Goncalves sold 7,000 shares at an average price of $30.61, totaling $214,270, which represents an 82.18% decrease in her ownership [4] Institutional Holdings - Institutional investors have increased their stakes in Oruka Therapeutics, with Woodline Partners LP boosting its stake by 46.9% and Fairmount Funds Management LLC increasing its holdings by 9.9% [5] - Institutional investors and hedge funds collectively own 56.44% of the company's stock [5] Company Overview - Oruka Therapeutics is a clinical-stage biopharmaceutical company focused on developing peptide-based therapies for oncology, utilizing a proprietary stapled peptide platform [7] - The lead candidate, ONCT-01, is currently in Phase 1 clinical trials for advanced solid tumors, assessing safety and preliminary efficacy [7]

Company Announcement - Oruka Therapeutics, Inc. has appointed Chris Martin to its Board of Directors, while Cameron Turtle has resigned effective December 11, 2025 [1][2] - The CEO, Lawrence Klein, expressed confidence in Martin's expertise to add value as the company advances its late-stage development programs, specifically ORKA-001 and ORKA-002 [2] Leadership Background - Chris Martin brings over 25 years of commercial experience, having most recently served as Chief Commercial Officer of Verona Pharma, which was acquired by Merck for approximately $10 billion in October 2025 [2] - At Verona, Martin was instrumental in building the commercial organization and launch strategy for Ohtuvayre (ensifentrine), which has seen rapid uptake for COPD treatment [2] Company Mission and Product Development - Oruka Therapeutics is focused on developing novel biologics aimed at treating chronic skin diseases, including plaque psoriasis, with a goal of achieving high rates of complete disease clearance [3] - The company aims to provide patients with the freedom from their conditions through infrequent dosing, potentially as little as once or twice a year [3] - Oruka is advancing a proprietary portfolio of antibodies engineered to target the core mechanisms of plaque psoriasis and other dermatologic and inflammatory diseases [3]

Core Insights - Oruka Therapeutics, Inc. has reported promising Phase 1 results for ORKA-001, indicating potential for once-per-year dosing, higher efficacy, and extended off-treatment remission for chronic skin diseases like plaque psoriasis [1][6][12] - The company has a strong cash position of approximately $500.9 million, providing a runway beyond key upcoming clinical readouts [1][7] - ORKA-001 and ORKA-002 are both advancing in clinical trials, with ORKA-001's Phase 2a trial expected to provide data in the second half of 2026 [1][2][6] Financial Performance - For Q3 2025, Oruka reported a net loss of $30.3 million, compared to a net loss of $28.6 million in Q3 2024, with R&D expenses increasing to $29.0 million from $25.7 million year-over-year [7][8][11] - General and administrative expenses rose to $5.1 million in Q3 2025 from $3.8 million in Q3 2024, primarily due to increased employee compensation and consulting fees [9] - Other income increased significantly to $3.8 million in Q3 2025, up from $0.8 million in Q3 2024, attributed to higher interest income from marketable securities [10] Clinical Development Updates - ORKA-001 demonstrated a half-life of approximately 100 days, significantly longer than risankizumab, enhancing the potential for less frequent dosing [6] - The Phase 2a trial, EVERLAST-A, is currently enrolling participants, with results expected in 2H 2026, while a Phase 2b trial, EVERLAST-B, is set to begin in 1H 2026 [6][14] - ORKA-002 is in a Phase 1 trial, with interim data anticipated around the end of 2025, and a Phase 2 trial planned for 1H 2026 [1][6][14] Strategic Outlook - The company aims to establish a new standard for treating chronic skin diseases, focusing on achieving high rates of complete disease clearance with infrequent dosing [12] - Oruka is also exploring a sequential combination regimen of ORKA-002 and ORKA-001, which could enhance treatment efficacy for psoriatic disease [14] - The company is progressing ORKA-003 through preclinical development, indicating a robust pipeline for future growth [14]

Financial Performance - For the three and nine months ended September 30, 2025, the company reported net losses of $30.3 million and $75.9 million, respectively[116]. - The net loss for the nine months ended September 30, 2025, was $75.9 million, a 31% increase from the net loss of $57.9 million in the prior period[157]. - The company has not generated any revenue from product sales to date and does not expect to do so in the foreseeable future[137]. - Net cash used in operating activities was $65.6 million for the nine months ended September 30, 2025, compared to $39.0 million for the same period in 2024[174][175]. - The company expects to incur significant operating losses and negative cash flow for the foreseeable future as it continues clinical development[170]. Cash and Financing - The company had cash, cash equivalents, and marketable securities totaling $500.9 million as of September 30, 2025, expected to fund operations for at least twelve months[117]. - As of September 30, 2025, the company had $500.9 million in cash, cash equivalents, and marketable securities[169]. - Net cash provided by financing activities was $170.0 million for the nine months ended September 30, 2025, primarily from the 2025 PIPE Financing[177]. - In October 2025, the company entered into a Sales Agreement to potentially raise up to $200.0 million through an at-the-market equity offering program[171]. - The company anticipates needing additional financing in the future to support ongoing research and development efforts[172]. Research and Development - ORKA-001, the lead program, demonstrated a half-life of approximately 100 days and showed complete inhibition of STAT3 signaling for 24 weeks in a Phase 1 trial[120]. - The Phase 2a clinical trial of ORKA-001, named EVERLAST-A, is expected to enroll approximately 80 patients, with a primary endpoint of PASI 100 at Week 16[121]. - A Phase 2b trial of ORKA-001, named EVERLAST-B, is planned to evaluate three dose levels, with dosing projected to begin before the completion of EVERLAST-A[122]. - ORKA-002, targeting IL-17A and IL-17F, is in Phase 1 trials with plans for a Phase 2 trial in hidradenitis suppurativa in the first half of 2026[124]. - The company expects research and development expenses to increase substantially in the foreseeable future as it continues to invest in its programs[139]. Expenses - Research and development expenses increased by $3.3 million, from $25.7 million for the three months ended September 30, 2024, to $29.0 million for the three months ended September 30, 2025, representing a 13% increase[148]. - Total operating expenses increased by $4.7 million, from $29.4 million for the three months ended September 30, 2024, to $34.1 million for the three months ended September 30, 2025, a 16% increase[146]. - General and administrative expenses rose by $1.4 million, from $3.8 million for the three months ended September 30, 2024, to $5.1 million for the three months ended September 30, 2025, a 36% increase[152]. - Personnel-related expenses in general and administrative increased by $1.3 million, from $2.4 million for the three months ended September 30, 2024, to $3.8 million for the three months ended September 30, 2025, a 55% increase[153]. - For the nine months ended September 30, 2025, total operating expenses increased by 52% to $87.6 million from $57.8 million for the same period in 2024[157]. - Research and development expenses rose by 47% to $73.0 million, up from $49.6 million, with external research expenses increasing by 20% to $45.6 million[159][160]. - General and administrative expenses increased by 77% to $14.6 million from $8.2 million, driven by a 135% rise in personnel-related expenses[162][164]. Corporate Actions - The company completed a merger with Pre-Merger Oruka on August 29, 2024, and changed its name from ARCA biopharma, Inc. to Oruka Therapeutics, Inc.[127]. - The company raised approximately $275.0 million in gross proceeds from a subscription agreement prior to the merger, incurring transaction costs of $20.5 million[128]. - In the 2024 PIPE Financing, the company raised approximately $188.7 million from the sale of 5,600,000 shares at $23.00 per share[130]. - In the 2025 PIPE Financing, the company raised approximately $169.6 million from the sale of 10,933,405 shares at $15.00 per share[132]. Accounting and Compliance - There were no changes to the company's critical accounting policies and significant judgments during the three months ended September 30, 2025[181]. - The company did not have any off-balance sheet arrangements as of September 30, 2025[182]. - The financial statements are prepared in accordance with U.S. GAAP, requiring estimates and assumptions that may affect reported amounts of assets and liabilities[180]. - The company is classified as a smaller reporting company and is not required to provide certain market risk disclosures[183]. Milestone Payments - The company incurred milestone payments of $7.0 million for ORKA-001 and $4.0 million for ORKA-002 as of September 30, 2025[136]. - The company has incurred a total of $12.0 million in non-refundable milestone payments under each License Agreement upon achieving certain clinical development milestones[135]. - The company has a royalty-bearing, world-wide, exclusive license to develop and commercialize antibodies targeting IL-23 and IL-17A/F under the License Agreements with Paragon[135].

Summary of Oruka Therapeutics Conference Call Company Overview - **Company**: Oruka Therapeutics (NasdaqGM: ORKA) - **Focus**: Advancing the standard of care in psoriatic disease with a pipeline centered around two co-lead assets, ORCA-001 and ORCA-002, both extended half-life monoclonal antibodies targeting plaque psoriasis, psoriatic arthritis, and related conditions [2][3] Key Products and Pipeline - **ORCA-001**: Modeled after Risankizumab (Skyrizi), targeting IL-23p19, with a 100-day half-life, aiming for once-a-year dosing [2][6][7] - **ORCA-002**: Modeled after Bimekizumab (Bimzelx), targeting IL-17A/F, with expected half-life around 75 days, aiming for twice-yearly dosing [2][17] - **Clinical Development**: - ORCA-001 is in phase 2 development, with readouts expected in the second half of next year [3][10] - ORCA-002 is in phase 1, with data anticipated around year-end [16][17] Market Opportunity - **Psoriasis Pipeline**: The current pipeline for psoriasis is relatively empty, presenting a significant opportunity for Oruka to introduce new biologics [4][5] - **Patient Preference**: The company believes that patients and physicians would prefer less frequent dosing with biologics over oral options, which are currently being explored by competitors [5] Clinical Data and Efficacy - **Efficacy Expectations**: - ORCA-001 aims for PASI 100 (fully clear skin) rates potentially in the 50s or 60s, compared to Skyrizi's 43% and Bimekizumab's 62% [11][12] - The innovative design of the phase 2A study includes a primary endpoint of PASI 100 at week 16, which is a novel approach in psoriasis trials [9][10] - **Durability of Response**: The study will also assess how long patients can maintain clear skin without additional doses, with expectations of 20-30% of patients remaining clear for two years or more after initial doses [10][14] Financial Position - **Cash Reserves**: The company is well-capitalized with over $500 million in cash, providing a runway through multiple significant inflection points, including phase 2 readouts for both programs [3][27] Future Directions - **Expansion into Hidradenitis Suppurativa (HS)**: The company plans to pursue HS after establishing its psoriasis programs, leveraging the success of Bimekizumab in psoriasis and psoriatic arthritis [21][22] - **Combination Therapy Concept**: ORCA-021 aims to explore the potential of using IL-17 for induction followed by IL-23 for maintenance, which has received positive feedback from experts [25][26] Conclusion - Oruka Therapeutics is positioned to capitalize on a significant market opportunity in psoriatic disease with its innovative pipeline of extended half-life monoclonal antibodies, backed by strong clinical data and a solid financial foundation. The company is strategically planning to expand its indications and explore combination therapies to enhance treatment outcomes for patients.