ORKA US Equity☆

Item 1A. Risk Factors 38

Item 1B. Unresolved Staff Comments 70

Item 1C. Cybersecurity 70

Item 2. Properties 70

Item 3. Legal Proceedings 70

Item 4. Mine Safety Disclosures 70

PART II

Item 6. [Reserved] 71

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 85

Item 8. Financial Statements and Supplementary Data F-1

Item 9A. Controls and Procedures 86

Item 9B. Other Information 87

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 87

PART III

Item 10. Directors, Executive Officers and Corporate Governance 88

Item 11. Executive Compensation 93

Item 14. Principal Accounting Fees and Services 108

PART IV

Item 15. Exhibits, Financial Statement Schedules 109

i

SPECIAL

NOTE REGARDING FORWARD-LOOKING STATEMENTS

This

Annual Report on Form 10-K, or Annual Report, contains “forward-looking statements” within the meaning of Section 27A of

the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”).

These forward-looking statements reflect the current views of Oruka Therapeutics, Inc. (“Oruka”, the “Company”,

“we”, or “us”) with respect to future events and are based on assumptions and subject to known and unknown risks

and uncertainties and other factors that may cause our actual results, performance, time frames or achievements to be materially different

from any future results, performance, time frames or achievements expressed or implied by the forward-looking statements. Factors that

might cause such a difference are disclosed in the section titled “Risk Factors” in this Annual Report. We caution readers

that any forward-looking statement is not a guarantee of future performance and that actual results could differ materially from those

contained in the forward-looking statement. These statements are based on current expectations of future events. You should evaluate

all forward-looking statements made in this Annual Report in the context of these risks and uncertainties. We caution you that the risks,

uncertainties and other factors referred to in this Annual Report may not contain all of the risks, uncertainties and other factors that

may affect our future results and operations. Moreover, we operate in a very competitive and rapidly changing environment, and new risks

and uncertainties emerge from time to time.

All

statements, other than statements of historical facts contained in this Annual Report, including, without limitation, statements regarding:

our future results of operations and financial position, business strategy, the length of time that we believe our existing cash resources

will fund our operations, our market size, our competition, our potential growth opportunities, our clinical development activities and

timeline, the efficacy and safety profile of our product candidates, the potential therapeutic benefits and economic value of our product

candidates, the timing and results of preclinical studies and clinical trials, the expected impact of macroeconomic conditions, including

inflation, increasing interest rates and volatile market conditions, current or potential bank failures, as well as global events, including

military conflicts and geopolitical tensions on our operations, and the receipt and timing of potential regulatory designations, approvals

and commercialization of product candidates, are forward-looking statements. The words “believe,” “may,” “will,”

“potentially,” “estimate,” “continue,” “anticipate,” “predict,” “target,”

“intend,” “could,” “would,” “should,” “project,” “plan,” “expect,”

and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although

not all forward-looking statements contain these identifying words. These forward-looking statements are based on information available

to us as of the date of this Annual Report and are subject to a number of risks, uncertainties and assumptions, including those described

in Item 1A, “Risk Factors” and elsewhere in this Annual Report. Moreover, we operate in a very competitive and rapidly changing

environment, and new risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the

impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ

materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties, and assumptions,

the forward-looking events and circumstances discussed in this Annual Report may not occur and actual results could differ materially

and adversely from those anticipated or implied in the forward-looking statements. While we believe that such information provides a

reasonable basis for these statements, such information may be limited or incomplete. Our statements should not be read to indicate that

we have conducted an exhaustive inquiry into, or review of, all relevant information. These statements are inherently uncertain, and

investors are cautioned not to unduly rely on these statements.

All

subsequent written or oral forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in

their entirety by the cautionary statements contained or referred to in this section. We do not undertake any obligation to release publicly

any revisions to these forward-looking statements to reflect events or circumstances after the date of this Annual Report or to reflect

the occurrence of unanticipated events, except as may be required under applicable U.S. securities laws. You should read this Annual

Report with the understanding that our actual future results, levels of activity, performance and events and circumstances may be materially

different from what we expect. If we do update one or more forward-looking statements, no inference should be drawn that we will make

additional updates with respect to those or other forward-looking statements.

Unless

the context indicates otherwise, as used in this Annual Report, the terms “Oruka,” “ARCA biopharma, Inc.,” “the

Company,” “we,” “us,” and “our” refer to Oruka Therapeutics, Inc., a Delaware corporation,

and its consolidated subsidiaries taken as a whole. “Oruka” and all product candidate names are our common law trademarks.

This Annual Report contains additional trade names, trademarks and service marks of other companies, which are the property of their

respective owners. We do not intend our use or display of other companies’ trade names, trademarks or service marks to imply a

relationship with, or endorsement or sponsorship of us by, these other companies.

All

references to “our product candidates,” “our programs” and “our pipeline” in this Annual Report refer

to the research programs with respect to which we have exercised the option to acquire intellectual property license rights to or have

the option to acquire intellectual property license rights to pursuant to those certain antibody discovery and option agreements by and

among the Company, Paragon Therapeutics, Inc. (“Paragon”) and Paruka Holding LLC (“Paruka”).

ii

PART

I

Item

1. Business.

Acquisition

of Pre-Merger Oruka

On

August 29, 2024 (the “Merger Closing”), we completed our acquisition (the “Merger”) of Oruka Therapeutics, Inc.

(“Pre-Merger Oruka”) pursuant to an Agreement and Plan of Merger and Reorganization, dated as of April 3, 2024 (the “Merger

Agreement”). Following the transactions contemplated by the Merger Agreement, Pre-Merger Oruka merged with and into Atlas Merger

Sub Corp., a wholly owned subsidiary of ARCA biopharma, Inc. (“ARCA”) and following that, Pre-Merger Oruka then merged with

and into Atlas Merger Sub II, LLC (“Second Merger Sub”), with Second Merger Sub being the surviving entity. Second Merger

Sub changed its corporate name to “Oruka Therapeutics Operating Company, LLC.” Pre-Merger Oruka was a pre-clinical stage

biotechnology company that was incorporated on February 6, 2024 under the direction of Peter Harwin, a Managing Member of Fairmount Funds

Management LLC (“Fairmount”), for the purposes of holding rights to certain intellectual property being developed by Paragon

Therapeutics, Inc. (“Paragon”). On August 29, 2024, we changed our name from “ARCA biopharma, Inc.” (“ARCA”)

to “Oruka Therapeutics, Inc.” and our Nasdaq ticker symbol from “ABIO” to “ORKA”.

Company

Overview

We

are a clinical-stage biopharmaceutical company focused on developing novel monoclonal antibody therapeutics for psoriasis (“PsO”)

and other inflammatory and immunology (“I&I”) indications. Our name is derived from or, for “skin,”

and arukah, for “restoration,” and reflects our mission to deliver therapies for chronic skin diseases that provide

patients the most possible freedom from their condition. Our strategy is to apply antibody engineering and format innovations to validated

modes of action, which we believe will enable us to improve meaningfully upon the efficacy and dosing regimens of standard-of-care medicines

while significantly reducing technical and biological risk. Our programs aim to treat and potentially modify disease by targeting mechanisms

with proven efficacy and safety involved in disease pathology and the activity of pathogenic tissue-resident memory T cells (“TRMs”).

Our

lead program, ORKA-001, is designed to target the p19 subunit of interleukin-23 (“IL-23p19”) for the treatment of PsO. Our

co-lead program, ORKA-002, is designed to target interleukin-17A and interleukin-17F (“IL-17A/F”) for the treatment of PsO,

psoriatic arthritis (“PsA”), and other conditions. These programs each bind their respective targets at high affinity and

incorporate half-life extension technology with the aim to increase exposure and decrease dosing frequency. We believe that our focused

strategy, differentiated portfolio, and deep expertise position us to set a new treatment standard in large I&I markets with continued

unmet need.

1

Our

Pipeline

ORKA-001

ORKA-001

is a high affinity, extended half-life monoclonal antibody (“mAb”) designed to target IL-23p19. IL-23 is a pro-inflammatory

cytokine that plays a critical role in the proliferation and development of T helper 17 (“Th17”) cells, which are the primary

drivers of several autoimmune and inflammatory disorders, including PsO. IL-23 is composed of two subunits: a p40 subunit that is shared

with IL-12 and a p19 subunit that is specific to IL-23. First-generation IL-23 antibodies bound p40 and inhibited both IL-12 and IL-23

signaling, while more recent IL-23 antibodies targeting the p19 subunit have shown improved efficacy and safety. Based on preclinical

evidence, we believe that ORKA-001 could achieve higher response rates than established therapies in PsO while requiring less frequent

dosing and maintaining the favorable safety profile of therapies targeting IL-23p19. ORKA-001 is engineered with YTE half-life extension

technology, a specific three amino acid change in the fragment crystallizable (“Fc”) domain to modify the pH-dependent binding

to the neonatal Fc receptor (“FcRn”). As a result, it has a pharmacokinetic profile designed to support a subcutaneous (“SQ”)

injection as infrequently as once or twice a year. In addition, emerging evidence suggests that IL-23 blockade can modify the disease

biology of PsO, possibly leading to durable remissions and preventing the development of PsA. We believe that the expected characteristics

of ORKA-001 increase its potential to deliver these disease-modifying benefits.

We

initiated dosing of healthy volunteers in a Phase 1 trial of ORKA-001 in the fourth quarter of 2024. We expect to share interim data

from the first-in-human trial in healthy volunteers, including initial pharmacokinetic data, in the second half of 2025 and initial efficacy

on patients with PsO in the second half of 2026. Based on recent precedent for PsO, we anticipate that the entire development program

from first-in-human to biologics license application (“BLA”) filing could take as little as six to seven years based

on the averages for recently approved medicines. However, we have no control over the length of time needed for United States Food and

Drug Administration (“FDA”) review, and this timeline could vary.

ORKA-002

ORKA-002

is a high affinity, extended half-life mAb designed to target IL-17A and IL-17F (“IL-17A/F”). IL-17 inhibition has become

central to the treatment of psoriatic diseases, including PsO and PsA, and has also shown efficacy in other I&I indications,

such as hidradenitis suppurativa (“HS”) and axial spondyloarthritis (“axSpA”). More recently, the importance

of inhibiting the IL-17F isoform along with IL-17A has become appreciated, and dual blockade with the recently approved therapy Bimzelx

(bimekizumab) has led to higher response rates in patients than blockade of IL-17A alone. ORKA-002 is designed to bind IL-17A/F at similar

epitopes, or binding sites, and affinity ranges as bimekizumab, but incorporates half-life extension technology that could enable more

convenient dosing intervals. We plan to initiate dosing of healthy volunteers in a Phase 1 trial of ORKA-002 in the third quarter

of 2025. We expect to share interim data from the first-in-human trial in healthy volunteers, including initial pharmacokinetic data,

in the first half of 2026.

2

We

view ORKA-002 and ORKA-001 as highly complementary. Patients with moderate-to-severe PsO

that have purely skin manifestations are most often treated with IL-23 inhibitors due to

the high efficacy and tolerability of this mechanism. However, for patients who also have

joint involvement or signs and symptoms of PsA, an IL-17 inhibitor is typically used due

to its efficacy in addressing both skin and joint symptoms. In addition, IL-17 inhibitors

are often used in patients with highly resistant skin symptoms that do not adequately resolve

through treatment with an IL-23 inhibitor. Furthermore, we have the potential opportunity

to administer ORKA-002 and ORKA-001 sequentially, called ORKA-021, to combine two attractive

features of each program: the rapid response of an IL-17 inhibitor with the ideal maintenance

profile of an IL-23 inhibitor. We believe that ORKA-001 and ORKA-002 provide the potential

to offer a highly compelling product profile for most patients with PsO and/or PsA, as well

as the opportunity to address additional I&I indications.

Additional

Pipeline Program

We

have a third mAb program, ORKA-003, designed to target an undisclosed pathway. Our strategy as a company is to remain highly focused

on I&I diseases, and specifically on inflammatory dermatology conditions. Our third program provides the potential for indication

expansion beyond PsO and may create combination opportunities with our more advanced programs.

Our

Team, Investors, and Paragon Collaboration

We

are led by a management team with significant experience in developing novel treatments for patients at biopharmaceutical companies such

as CRISPR Therapeutics, Celgene, Novartis, CymaBay Therapeutics and Protagonist Therapeutics. Together, our team has a proven track record

of building successful biotech organizations in high-growth environments.

Pre-Merger

Oruka was founded in February 2024 by leading healthcare investor Fairmount. Fairmount founded Paragon in 2021 to conduct biologics

discovery and optimization, including acting as the firm’s discovery engine for biologics that potentially overcome limitations

of existing therapies. We have entered into license agreements with Paragon pursuant to which Paragon granted us a royalty-bearing, world-wide,

exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 outside

of the field of inflammatory bowel disease for ORKA-001 and for ORKA-002, certain antibodies and products targeting IL-17A/F.

Our

Strategy

To

achieve our goal of developing leading therapeutic antibodies for patients with inflammatory skin diseases, we are applying antibody

engineering to validated modes of action. We believe this approach will enable us to improve meaningfully upon the efficacy and convenience

of standard-of-care medicines while significantly reducing technical and biological risk. The key elements of our strategy include:

3

We

believe that pursuing the focused strategy outlined above will help us to succeed in our mission of offering patients living with PsO,

PsA, and other dermatologic and inflammatory diseases the greatest possible freedom from their condition.

Targeting

IL-23 and IL-17 to Treat Multiple I&I Indications

Our

programs benefit from significant advances in the understanding of the biology of I&I diseases over the past four decades. ORKA-001

and ORKA-002 are designed to target two key cytokines that play a related role in multiple indications. IL-23 is an upstream regulator

of Th17 cells, a pro-inflammatory subset of T helper cells characterized by their production of IL-17. IL-23 has a critical role in maintaining

Th17 cells in the tissue as well as activating these cells to secrete IL-17, which acts downstream to trigger inflammation and other

disease symptoms. Th17 cells are involved in PsO, PsA, HS, axSpA, and many other diseases. They play a particularly central role in PsO

and PsA. The diagram below depicting the immunopathogenesis of PsO provides an example of how Th17 cells can mediate disease and how

blocking IL-23 or IL-17 can break the inflammatory cycle that drives disease.

4

Immunopathogenesis

of PsO and the role of IL-23 and IL-17

PsO

develops when environmental triggers and a genetic predisposition combine to cause activation of an inflammatory cycle in the skin that

leads to the formation of plaques and other disease manifestations. This process begins with the aberrant activation of the dendritic

cells (“DCs”), specifically those producing IL-23 and other cytokines like IL-1β, IL-21, TNF-α, and IL-12. These

cytokines induce the differentiation of Th17 cells, as well as other cell types, such as T helper type 1 (“Th1”) cells that

produce IFNγ and TNF-α and T helper type 22 (“Th22”) cells that produce IL-22. IL-23 plays a key role in the

differentiation and activation of Th17 cells to secrete IL-17, as well as Th22 cells to produce IL-22. IL-17 and these other cytokines

induce keratinocyte hyperproliferation leading to plaque formation and a feedforward inflammatory response, with changes in gene expression

in keratinocytes, the production of antimicrobial peptides, and neutrophil recruitment driving further inflammation. While many cytokines

and cell types contribute to the pathogenesis of PsO, the IL-23/IL-17 axis plays an important role, as supported by the success of therapies

targeting this axis.

While

the successful treatment of PsO — for instance, with mAbs targeting IL-23 or IL-17 — can result in lesional

skin returning to an apparently normal state, disease tends to recur at previously affected sites following cessation of therapy, suggesting

a mechanism of “immunological memory” that predisposes individuals to recurrence in the same locations. Evidence suggests

that pathogenic TRMs play a critical role in this memory. TRMs may arise from the Th17 cells and other cells that drove disease in the

first place and remain in their resident tissue, in this case the epidermis and dermis, for long periods of time. Upon a disease trigger,

these TRMs can actively produce proinflammatory cytokines, causing disease recurrence. IL-23 appears to play an important role in maintaining

and potentiating TRMs, as indicated by the depletion of TRMs following treatment with an IL-23 inhibitor but not an IL-17 inhibitor,

which may explain the longer remissions observed with IL-23 inhibitors following withdrawal of therapy. This type of data has raised

the prospect that efficient IL-23 blockade could modify the disease biology of PsO, possibly leading to durable remissions.

5

The

scientific discoveries that refined our understanding of the immunopathogenesis of PsO have led to waves of therapeutic advances, ultimately

leading to today’s standard of care. Before the 1980s, PsO was not even thought of as an immunologic disease, but rather a disease

of keratinocyte dysfunction, leading to treatments such as phototherapy, methotrexate, and retinoids. The discovery in the 1980s that

PsO results from immune dysfunction led to the use of broad immunosuppressants like cyclosporine. From 1990 to 2008, it was believed

that Th1 cells were the predominant mediators of the disease, which led to the use of biologics targeting TNF-α such as Enbrel

(etanercept) and Humira (adalimumab). Finally, the revelation that PsO is driven principally by Th17 cells resulted in the development

of the primary therapies used today, which target IL-23 and IL-17. This increasingly refined understanding of the disease has narrowed

the standard of care from broad immunosuppressive agents (such as cyclosporine) to more specific immunomodulators (TNF-α inhibitors)

to precise biologic therapies targeting the key cytokines involved in disease pathology (IL-23 and IL-17 inhibitors), with each new therapeutic

class raising the bar on both safety and efficacy.

Biologic

therapies, especially mAbs, are now mainstays in the treatment of a wide variety of I&I diseases, including PsO and PsA. Therapies

that have improved upon efficacy and/or reduced dosing frequency have achieved the most commercial success, even when launched many years

after other biologics. Enbrel was first approved for PsO in 2004 with a weekly maintenance dosing schedule. Four years later, Humira

was approved for PsO with an every-other-week (Q2W) dosing schedule. Stelara (ustekinumab) was approved a year later with similar Phase 3

data to Humira, but with a significantly improved dosing schedule of every twelve weeks (Q12W). Several drugs for PsO have been

approved since 2009 that demonstrated higher efficacy in their pivotal studies compared to Stelara, but with more burdensome dosing schedules,

including Tremfya (guselkumab), which has a dosing schedule of every eight weeks (Q8W), and Cosentyx (secukinumab) and Taltz (ixekizumab),

which have dosing schedules of every four weeks (Q4W). While these therapies have all become generally successful products, the

most commercially successful drug in the PsO market today is Skyrizi (risankizumab), which combines Stelara’s Q12W dosing schedule

with improvements in efficacy, as evidenced by a higher psoriasis area severity index (PASI) score of PASI 90 and PASI 100 rates (i.e.,

a 90% improvement in PASI score and a 100% improvement in PASI score (complete clearance), respectively) in clinical trials. In addition,

Bimzelx (bimekizumab), approved by the FDA in 2023, has shown evidence of efficacy that exceeds even Skyrizi, though with a less convenient

Q8W dosing schedule. Although many biologics have entered the PsO market over the past two decades, new entrants have had significant

commercial success when they have improved upon efficacy and/or dosing frequency, and room remains to improve in both areas to set a

new standard for the treatment of PsO.

Biologics

have raised the bar on the standard of care in PsO, but leave room for improvement

The

biology driving PsO and PsA is well understood today, and the standard of care has progressed dramatically. We believe that it is unlikely

that a novel mechanism will emerge that is as safe and efficacious as targeting the IL-23/IL-17 axis. Therefore, we believe that innovation

now should be focused on optimizing the product profile that can be offered to patients. While much effort is being directed toward daily

oral formats to inhibit this axis, oral medicines have yet to match the efficacy of biologics. We believe that a better biologic with

a longer dosing interval and the potential for improved efficacy will present a more attractive product profile for most patients.

6

Overview

of Psoriasis (PsO)

PsO

is a chronic autoimmune skin disorder that affects an estimated 125 million people worldwide with steadily increasing prevalence,

estimated to be around 2 – 3% of the population currently, according to the World Psoriasis Day consortium. It is

the largest pharmaceutical market within dermatology, with annual sales of approximately $25.0 billion in 2022, which is estimated

to grow to $32 billion by 2028. The most common form of PsO is plaque psoriasis. Patients with chronic plaque psoriasis have well-demarcated,

erythematous plaques with overlying, coarse, silvery-scaled patches. These plaques can occur anywhere on the body, though are typically

found on the scalp, extensor areas of the knees and elbows, and gluteal cleft. Involvement of the palms, soles, or nails, and intertriginous

areas, including the genitals, can also occur and can be particularly difficult to treat. Between one-quarter and one-half of PsO patients

have moderate disease, defined as having 3% to 10% of the body surface area (“BSA”) involved, or severe disease, defined

as having more than 10% BSA involvement. The chronic inflammation in PsO is associated with multiple comorbidities, including PsA, obesity,

metabolic syndrome, hypertension, diabetes, and atherosclerotic cardiovascular disease.

As

discussed earlier, PsO is a complex immune-mediated disease driven primarily by Th17 cells and the cytokines IL-23 and IL-17. The interplay

of environmental and behavioral risk factors and genetics is believed to trigger PsO. Multiple lines of evidence support a genetic

component to the disease, including the observation that approximately 40% of patients with PsO and PsA have a family history of the

disease and the identification of multiple susceptibility loci, many containing genes related to the regulation of the immune system,

in genome-wide association studies.

Current

PsO Treatments and Limitations

While

patients with mild PsO typically rely on topical corticosteroids or oral therapies like Otezla (apremilast), these agents often do not

provide an adequate response for patients with moderate-to-severe PsO. As a result, the American Academy of Dermatology-National

Psoriasis Foundation recommends biologics as first-line therapy for moderate-to-severe PsO.

Several

classes of biologic therapies have been approved for PsO over the past 20 years, resulting in progressively more complete symptom

relief. Efficacy in PsO is typically measured via the PASI scoring system. The first biologics approved for PsO were tumor necrosis alpha

(“TNF-α”) inhibitors such as Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab), which achieved a

PASI score of PASI 90 at 16 weeks in around 25 – 50% of patients and a PASI score of PASI 100 in around

5 – 20% of patients. Stelara (ustekinumab), which targets the p40 subunit of IL-23 that is shared with IL-12, was approved

next and achieved efficacy on par with Humira. IL-17 inhibitors Cosentyx (secukinumab), Taltz (ixekizumab), and Siliq (brodalumab) followed

and achieved responses of PASI 90 in around 70% of patients and PASI 100 in around 40% of patients with some risk of certain

side effects such as oral candidiasis. Most recently, IL-23p19 inhibitors such as Ilumya (tildrakizumab), Tremfya (guselkumab), and Skyrizi

(risankizumab) have achieved responses of PASI 90 in around 70 – 80% of patients and PASI 100 in around 30 – 50%

of patients with highly tolerable profiles. Finally, IL-17A/F inhibitors such as Bimzelx (bimekizumab) have recently shown even higher

response rates than IL-23 inhibitors, but with slightly less tolerable profiles.

Treatment

expectations in PsO have evolved progressively with this continued innovation. A 75% improvement in PASI score was previously thought

to be an adequate depth of response, and weekly SQ dosing was viewed as acceptable. With each subsequent generation of innovation, patient

and caregiver expectations have advanced. Today, Skyrizi (risankizumab) is widely viewed as the leader in PsO biologic therapy. In Phase 3

clinical trials, 43% and 58% of patients achieved PASI 100 at 16 and 52 weeks, respectively, with SQ maintenance dosing every three months.

Most recently, Bimzelx (bimekizumab) has shown evidence of efficacy that exceeds even Skyrizi, achieving a 64% PASI 100 rate at 16 weeks

in Phase 3 trials. However, the increased efficacy comes with a less convenient Q8W dosing schedule and an increased risk of certain

side effects, most notably oral candidiasis. While agents like Skyrizi and Bimzelx reflect the remarkable advancement in PsO treatment,

there remains significant unmet need. Approximately half of moderate-to-severe PsO patients do not achieve full skin clarity, and while

early signs are present, the promise of disease modifying therapy remains unrealized. In addition, a continued desire for more convenient

dosing options has driven significant interest in orally delivered medicines targeting these same pathways. However, oral therapies have

yet to match the efficacy and safety profile of biologics. We believe that ORKA-001 and ORKA-002 could represent the next step in biologic

innovation in PsO, with the potential for higher rates of complete skin clearance, more durable remissions, and markedly more convenient

dosing regimens.

7

Overview

of Psoriatic Arthritis (PsA)

PsA

is a chronic inflammatory condition that affects both the skin and joints, and often coexists with PsO. Around a quarter to a third

of patients with moderate-to-severe PsO also have PsA. Most individuals develop PsO before being diagnosed with PsA, with a median

gap of seven to eight years between the diagnosis of skin and joint disease, though in up to 30% of patients with PsA, joint symptoms

appear before or simultaneously with skin manifestations. Patients with PsA present with joint pain, stiffness, and swelling affecting

the peripheral joints, axial skeleton, or both. Enthesitis, dactylitis, nail lesions, fatigue, and ocular inflammation all occur commonly.

PsA can lead to irreversible joint damage, including bony fusion across a joint (ankylosis). The pathogenesis of PsA is likely to be

closely related to the mechanisms that underlie PsO. Like PsO, the exact cause of PsA remains unknown, but environmental triggers,

including infection and trauma, and genetic factors play a role.

Current

PsA Treatments and Limitations

Effective

treatment of PsA requires a coordinated approach to address the unique combination of disease manifestations each patient has, which

can include peripheral and axial arthritis, enthesitis, dactylitis, and skin and nail involvement. Many patients with milder disease

symptoms will start with nonsteroidal anti-inflammatory drugs (“NSAIDs”) and/or local treatments to address specific disease

manifestations. However, those with more moderate or severe disease and/or multidomain involvement will typically receive a biologic

therapy targeting TNF-α or IL-17, or less commonly an oral Janus kinase (“JAK”) inhibitor. Comorbid conditions can

also influence treatment selection. For example, an IL-17 inhibitor would be preferred for a patient with significant skin involvement,

but not for patients with IBD or ocular symptoms, where a TNF-α inhibitor would be preferred. The most common endpoint used to

measure the efficacy of TNF-α or IL-17 inhibitors in PsA is ACR response, or the proportion of patients achieving a specified percent

improvement in American College of Rheumatology (“ACR”) score, which measures peripheral joint disease. Approved TNF-α

inhibitors, including Humira (adalimumab) and Cimzia (certolizumab), achieved a placebo-adjusted ACR50 response of around 30 – 35%

at 24 weeks with Q2W dosing. Approved IL-17 inhibitors, including Cosentyx (secukinumab) and Taltz (ixekizumab), achieved a slightly

lower placebo-adjusted ACR50 response of around 25 – 30% at 24 weeks, but with more convenient Q4W dosing.

Bimzelx (bimekizumab), which was recently approved in the United States for PsA, achieved a placebo-adjusted ACR50 response of approximately

35% at 16 weeks with Q4W dosing. A significant fraction of patients with PsA still do not achieve a satisfactory response with available

therapies, and even the most convenient regimens require monthly SQ dosing.

Overview

of additional opportunities

In

addition to PsO and PsA, inhibition of IL-23 or IL-17 has demonstrated efficacy in a number of additional I&I indications, including

HS and axSpA.

HS

is a chronic inflammatory skin disease characterized by lesions that include deep-seated nodules and abscesses, draining tracts, and

fibrotic scars that occur most commonly in intertriginous areas, such as the armpits and groin. Due to the associated pain, sensitive

locations, drainage, odor, and scarring, this condition can have a particularly negative psychosocial impact on affected individuals.

HS is believed to be underdiagnosed and could have a prevalence well above 1% worldwide. Treatment varies depending on severity and can

include topical and systemic antibiotics, hormone therapy, immune modulators, and surgery. Humira (adalimumab) was the only FDA-approved

medication for the treatment of moderate-to-severe HS from its approval in 2015 until the approval of Cosentyx (secukinumab) in October 2023

and Bimzelx (bimekizumab) in November 2024. Now multiple other biologics are advancing through development and have demonstrated encouraging

data in Phase 2 clinical trials, though a significant fraction of patients still do not achieve adequate responses.

axSpA

is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints that comprise the axial skeleton. The disease

causes severe pain, stiffness, and fatigue, and can have additional clinical manifestations like uveitis, enthesitis, peripheral arthritis,

and PsO. Patients with axSpA may develop further structural damage in their spine, which can lead to the fusion of vertebra (spinal

ankylosis), which has a massive negative impact on mobility, physical function, and quality of life. The overall prevalence of axSpA

is estimated to be around 1% in the United States. Treatment of axSpA starts with physical therapy and NSAIDs. If patients do not

have an adequate response to NSAIDs, a TNF-α inhibitor is typically used, followed by an IL-17 inhibitor, such as Cosentyx (secukinumab),

Taltz (ixekizumab), or Bimzelx (bimekizumab), or less frequently a JAK inhibitor. Patients often need to cycle through therapies over

time due to inadequate responses or loss of response.

8

Our

Solution: Half-Life Extension and Antibody Engineering Technologies

Our

antibody engineering campaigns are designed to optimize multiple attributes in parallel: binding affinity, potency in a variety of assays,

developability, and consistently extended serum half-life in non-human primates (“NHPs”). Half-life extension is possible

by modifying the pH-dependent binding affinity of the antibody Fc domain for FcRn. A primary mechanism of elimination of antibodies from

the serum is through pinocytosis and degradation in the lysosomes of cells. Throughout this process, antibodies can be recycled back

into the serum by binding to FcRn while they are in endosomes. The interior of the endosome is acidic, and therefore the efficiency of

this recycling process depends on the ability of the antibody Fc domain to bind to FcRn at low pH. If this low pH binding is efficient

enough, antibody recycling can be favored over degradation, potentially resulting in a much longer serum half-life.

Antibody

engineers have discovered methods of modifying the Fc domain to optimize the efficiency of recycling via FcRn binding. Several engineering

strategies have been identified over the past two decades, with the so-called “YTE” mutations (M252Y/S254T/T256E) and “LS”

mutations (M428L/N434S) being the most frequently used. Importantly, while these strategies have been known for some time, it was only

relatively recently that enough clinical precedent was established to provide confidence in how these mutations perform in humans. Two

products incorporating YTE modification were approved in 2023 by the FDA, Beyfortus (nirsevimab) and Evusheld (tixagevimab and cilgavimab),

and several more candidates are in clinical trials. Two products using LS mutations were approved in 2021 and 2022, Xevudy (sotrovima)

and Ultomiris (ravulizumab), respectively, and several more candidates are in clinical trials. Based on clinical data in humans, antibodies

with YTE mutations typically have a half-life that is two to four times longer than wildtype antibodies. In addition, preclinical data

in NHPs can be used to predict the approximate half-life in humans, with the human half-life equaling around two to four times the

NHP half-life.

Clinical

experience with YTE-modified mAbs predicts significant half-life extension over wildtype mAbs

While

this increasing body of clinical precedent serves to validate half-life extension, we do not yet have clinical data showing that the

introduction of these amino acid substitutions in our programs leads to a longer serum half-life. However, we aim to establish this favorable

pharmacokinetic profile early in the clinical development of our product candidates.

9

ORKA-001

Summary

ORKA-001

is a high affinity, extended half-life mAb designed to target the p19 subunit of IL-23. Based on preclinical data generated to date,

we believe ORKA-001 has the potential to become the leading IL-23 inhibitor and achieve an optimal product profile in PsO consisting

of the following:

We

believe that this target profile for ORKA-001 could offer improved freedom from disease to many patients affected by PsO and represent

a step forward in the standard of care.

10

Preclinical

Data

We

evaluated ORKA-001 in numerous preclinical studies for several key features:

Potency

that matches or exceeds Skyrizi (risankizumab) in vitro

We

have tested the potency of ORKA-001 in vitro in multiple assays, including assays evaluating the inhibition of IL-17 release from

human peripheral mononuclear blood cells, in comparison to risankizumab generated recombinantly based on amino acid sequences from patent

filings. Based on the results of these experiments, we believe ORKA-001 binds a similar epitope as risankizumab with similar potency.

ORKA-001

binds to a similar epitope as risankizumab with similar potency

Significant

half-life extension in NHPs that could enable a maintenance dosing interval of once or twice a year in humans

We

assessed ORKA-001 in NHPs in comparison to risankizumab generated recombinantly based on amino acid sequences from patent filings. ORKA-001

had a significantly longer half-life, reaching over 30 days with SQ administration. Based on clinical experience with YTE-modified

mAbs and pharmacokinetic modeling, we believe that this half-life extension could enable dosing once or twice per year, as shown in the

figure below.

11

The

incorporation of YTE mutations significantly extends half-life in NHPs, which could enable once or twice yearly dosing

In

addition to enabling less frequent dosing, an extended half-life would increase the exposure of ORKA-001, which has the potential to

increase efficacy. Based on published literature, Skyrizi (risankizumab) demonstrates a clear relationship between antibody exposure

and efficacy, with higher average serum antibody concentration correlating with higher PASI 90 and PASI 100 rates short-term (at 16 weeks)

and long-term (at 52 weeks), as shown for PASI 100 in the figure below. In addition, the KNOCKOUT study, which evaluated two- and

four-times higher doses of Skyrizi than the approved regimen, yielded some of the highest PASI 100 rates observed to date, reaching 67%

at 16 weeks. Based on our pharmacokinetic modeling, ORKA-001 could achieve four-fold higher average exposures than the approved

Skyrizi regimen over the first 16 weeks and over two-fold higher average exposures at steady-state, exceeding even the exposures

in KNOCKOUT. Based on the exposure-response relationship observed with other IL-23 inhibiting antibodies, we believe that these

increased exposures could result in higher efficacy.

ORKA-001

is projected to extend the exposure-response relationship established by studies of Skyrizi

Safety

in vitro and in vivo

We

have evaluated ORKA-001 in several in vitro and in vivo preclinical studies to assess safety. In addition, we have

a nonclinical program to characterize the toxicology, toxicokinetics, and anti-drug antibody profile of ORKA-001 in NHPs. Our nonclinical

program supported the initiation of our Phase 1 clinical trial for ORKA-001 and our continuing clinical development.

12

Characteristics

that support ease of manufacturing and potentially enable high-concentration formulations

Finally,

we have assessed a variety of attributes essential for manufacturability and high-concentration formulation, including viscosity, solubility,

and stability, among others. ORKA-001 shows evidence of desirable properties across these characteristics, which we believe will enhance

our ability to manufacture ORKA-001 successfully and consistently and to deliver high doses of ORKA-001 subcutaneously using convenient,

low-volume presentations.

Clinical

Development

ORKA-001

We

dosed the first participants in a Phase 1 clinical trial of ORKA-001 in healthy volunteers in the fourth quarter of 2024. This trial

is a double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability, and pharmacokinetics of ORKA-001

in healthy volunteers. The trial is expected to enroll approximately 24 healthy volunteers across three subcutaneous dose cohorts. We

expect to share interim data from this trial in the second half of 2025. We believe this data has the potential to provide key validation

of initial safety and pharmacokinetics data, including half-life, to support extended dosing intervals.

We

plan to initiate a Phase 2a proof-of-concept study of ORKA-001 in moderate-to-severe PsO in the second half of 2025. We believe that

several aspects of PsO facilitate clinical development, including well-established, reproducible endpoints based on PASI scores, low

placebo rates, particularly with PASI 90 and PASI 100, a rapid efficacy readout at 16 weeks, and potentially rapid enrollment due to

the large patient population. Our Phase 2a clinical trial is anticipated to evaluate the safety and efficacy of a single dose level of

ORKA-001 versus placebo in approximately 80 subjects, followed by randomization to one of two maintenance dosing arms. In one maintenance

arm, subjects will receive ORKA-001 every six months. In the other, subjects will receive only induction dosing to assess the length

of time patients maintain clear skin, which could support once-yearly dosing or even longer-term durability in some patients. The anticipated

primary endpoint is PASI 100 at Week 16. After completing the trial, subjects may have the option to roll over to an open-label extension

study. We expect to share initial data from the Phase 2a trial in the second half of 2026. We believe this data has the potential to

inform efficacy at Week 16, as well as later timepoints, and provide us information on preliminary durability, including the potential

for extended dosing intervals and longer-term remissions.

ORKA-002

Summary

ORKA-002

is a high affinity, extended half-life mAb designed to target IL-17A/F. Dual inhibition of both IL-17A and IL-17F has shown superior

efficacy compared to IL-17A inhibition alone in PsO and other indications, as shown by the performance of Bimzelx (bimekizumab) compared

to Cosentyx (secukinumab) and Taltz (ixekizumab) in Phase 3 trials. These therapies all utilize Q4W maintenance dosing in PsO and

PsA, except Bimzelx, where Q8W maintenance dosing in PsO patients <120 kg is recommended. By binding IL-17A/F at similar epitopes

and affinity ranges as Bimzelx while incorporating half-life extension technology to potentially enable dosing two to three times a year

in PsO and PsA, we believe that ORKA-002 could become the leading therapy in the IL-17 class.

Preclinical

Data

The

preclinical program we are conducting for ORKA-002 mirrors that for ORKA-001 and spans potency, pharmacokinetics, safety, and manufacturing

characteristics. Based on the results of these experiments, we believe ORKA-002 has the potential for comparable potency to bimekizumab,

but with a significantly longer half-life, which we believe could support dosing two or three times per year based on extrapolation from

clinical precedent and pharmacokinetic modeling.

13

Clinical

Development Plans

We

plan to initiate dosing of healthy volunteers in a Phase 1 trial of ORKA-002 in the third quarter of 2025. As with ORKA-001, initial

data on ORKA-002 in healthy volunteers has the potential to provide key validation of both early safety and pharmacokinetics to support

extended dosing intervals. Though clinical development of ORKA-002 will initially focus on one lead indication, we plan to evaluate ORKA-002

in a range of indications over time. We see ORKA-002 as highly complementary to ORKA-001, with the potential to provide an optimal therapy

for the approximately one-quarter to one-third of moderate-to-severe PsO patients who have PsA, as well as for PsO patients with highly

resistant skin symptoms that do not respond adequately to an IL-23 inhibitor. Furthermore, ORKA-002 could address indications beyond

PsO, including PsA with limited skin involvement, HS, axSpA, and additional I&I diseases.

ORKA-021

The

IL-17 and IL-23 classes each have distinct advantages. IL-17 inhibitors tend to have the fastest onset and highest peak response, while

IL-23 inhibitors have less frequent dosing and better durability and safety. Combining the two mechanisms sequentially has the potential

to provide two attractive features of each program: the rapid response of an IL-17 inhibitor with the ideal maintenance profile of an

IL-23 inhibitor. As a result, following ORKA-002 and ORKA-001, we plan to explore a sequential combination regimen of ORKA-002 and ORKA-001,

called “ORKA-021.”

Additional

Pipeline Program

We

have a third mAb program, ORKA-003, that targets an undisclosed pathway. A core tenet of our strategy is to remain highly focused on I&I

diseases, and specifically on inflammatory dermatology conditions. ORKA-003 provides the potential for indication expansion beyond PsO

as well as combination opportunities with our more advanced programs. In the future, we may add additional programs to our portfolio

beyond ORKA-001, ORKA-002, ORKA-021 and ORKA-003 that fit our strategic focus.

Intellectual

Property

We

strive to protect the proprietary programs and technologies that we believe are important to our business, including seeking and maintaining

patent protection intended to cover the composition of matter of our programs, their methods of use and manufacture, related technologies,

diagnostics, and other inventions.

Paragon

has filed, on our behalf, provisional patent applications, and we have filed non-provisional patent applications, and may file additional

patent applications directed to antibodies that target IL-23, including applications covering composition of matter, pharmaceutical formulations,

and methods of using such antibodies, including ORKA-001. In addition, Paragon has filed, on our behalf, provisional patent applications,

and we may file additional patent applications directed to antibodies that target IL-17, including applications covering composition

of matter, pharmaceutical formulations, and methods of using such antibodies, including ORKA-002. We have exclusive rights to ORKA-001

and ORKA-002 and the corresponding IL-23 and IL-17 patent applications pursuant to license agreements with Paragon. If the patent applications

mature into one or more issued patents covering ORKA-001 or ORKA-002, we would expect those patents to expire in 2045, absent any applicable

patent term adjustments or extensions.

Commercial

Should

any of our product candidates be approved for commercialization, we intend to develop a plan to commercialize them in the United States

and other key markets, through internal infrastructure and/or external partnerships in a manner that will enable us to realize the full

commercial value of our programs. Given our stage of development, we have not yet established a commercial organization or distribution

capabilities. We have exclusive worldwide rights to develop and commercialize ORKA-001 and ORKA-002 pursuant to license agreements with

Paragon.

14

Manufacturing

We

do not currently own or operate facilities for product manufacturing, testing, storage, and distribution. We have contracted and expect

to continue to contract with third parties for the manufacture and distribution of our product candidates. Because we rely on contract

manufacturers, we employ personnel with extensive technical, manufacturing, analytical, and quality experience. Our team has deep knowledge

and understanding of the regulations that govern manufacturing, documentation, quality assurance, and quality control of drug supply

that are required to support our regulatory filings.

Competition

The

biotechnology and biopharmaceutical industries are characterized by continuing technological advancement and significant competition.

While we believe that our programs, technology, development experience and scientific knowledge provide us with competitive advantages,

we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and

private research institutions, among others. Any product candidates that we successfully develop and commercialize will compete with

existing therapies and therapies that may become available in the future. Many of the companies with which we are currently competing

or will compete against in the future have significantly greater financial resources and expertise in research and development, manufacturing,

preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers

and acquisitions in the pharmaceutical and biotechnology industry may result in even more resources being concentrated among a smaller

number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative

arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific

and management personnel, establishing clinical trial sites, patient enrollment for clinical trials as well as in acquiring technologies

complementary to, or necessary for, our programs.

Key

competitive factors affecting the success of all our product candidates that we develop, if approved, are likely to be efficacy, safety,

convenience, presentation, price, the level of generic competition, and the availability of reimbursement from government and other third-party

payors. Our competitors may also obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval

for our products, which could result in our competitors establishing a strong market position before we are able to enter the market.

Specifically,

there are several companies developing or marketing treatments that may be approved for the same indications and/or diseases as our two

most advanced programs, ORKA-001 and ORKA-002, including major pharmaceutical companies. We do not yet have clinical data for any of

our programs and there can be no assurance that our programs will have similar or comparable results.

There

are several approved biologic therapies for the treatment of moderate-to-severe PsO. These include mAbs targeting IL-23, such as

Skyrizi (risankizumab) from AbbVie, Tremfya (guselkumab) from Janssen, and Ilumya (tildrakizumab) from Sun Pharma, also marketed as Ilumetri

by Almirall in Europe, which all target the p19 subunit, and Stelara (ustekinumab) from Janssen, which targets the p40 subunit; mAbs

targeting IL-17, such as Bimzelx (bimekizumab) from UCB, which targets IL-17A/F, Cosentyx (secukinumab) from Novartis and Taltz (ixekizumab)

from Eli Lilly, which both target IL-17A, and Siliq (brodalumab) from Ortho Dermatologics, also marketed as Kyntheum by LEO Pharma in

Europe, which targets IL-17 receptor/A; and biologics targeting TNF-α, such as Humira (adalimumab) from AbbVie, Enbrel (etanercept)

from Amgen, and Remicade (infliximab) from Janssen, and various biosimilar versions of each. In addition, there are several approved

oral medicines in these indications, including the phosphodiesterase-4 (PDE4) inhibitor Otezla (apremilast) from Amgen and the tyrosine

kinase 2 (TYK2) inhibitor Sotyktu (deucravacitinib) from Bristol-Myers Squibb. Many of these therapies also are approved or in development

for PsA, HS, axSpA, and other I&I indications.

In

addition, we are aware of several product candidates in clinical development for moderate-to-severe PsO, along with PsA, HS, axSpA, and

other indications. These include the biologics picankibart from Innovent Biologics targeting IL-23p19 and sonelokimab from MoonLake Immunotherapeutics

targeting IL-17A/F. Also, there are several oral agents in development, including JNJ-2113 from Janssen targeting the IL-23 receptor,

DC-853 from Eli Lilly targeting IL-17A, and TAK-279 from Takeda and ESK-001 from Alumis, both targeting TYK2.

15

Significant

Agreements

Paragon

Therapeutics – Option Agreements

In March 2024, we entered

into two antibody discovery and option agreements (“Option Agreements”) with Paragon and Paruka Holding, LLC (“Paruka”).

Paruka is an entity formed by Paragon as a vehicle to hold equity in our Company in order to share profits with certain employees of Paragon.

Under the terms of each agreement, Paragon identifies, evaluates, and develops antibodies directed against certain mutually agreed therapeutic

targets of interest to us. From time to time, we can choose to add additional targets to the collaboration upon agreement with Paragon

and Paruka. Under the Option Agreements, we have the exclusive option to, on a research program-by-research program basis, be granted

an exclusive, worldwide license to all of Paragon’s right, title, and interest in and to the intellectual property resulting from

the applicable research program to develop, manufacture, and commercialize the antibodies and products directed to the selected target(s) (each,

an “Option”). We have initiated certain research programs with Paragon that generally focus on discovering, generating, identifying

and/or characterizing antibodies directed to a particular target (each, a “Research Program”), including for IL-23 and IL-17A/F

for ORKA-001 and ORKA-002, respectively. Our exclusive option with respect to each Research Program is exercisable at our sole discretion