Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor

Inclusion Criteria:

• Body weight ≥ 40 to ≤ 140 kg for all cohorts.

• Diagnosis of RA for ≥ 3 months fulfilling the 2010 American College of Rheumatology (ACR)/European Union League Against Rheumatism (EULAR) classification criteria forRA and that is categorized as ACR RA functional Class 1-3.

• Treated with a biological disease-modifying anti-rheumatic drug (bDMARDs) AND/ORJanus kinase inhibitor (JAKi) therapy for RA for ≥ 3 months and had inadequateresponse or had to discontinue bDMARD AND/OR JAKi therapy due to intolerance ortoxicity, regardless of treatment duration.

• Currently receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks before the firstdose of investigational product.

1. The following csDMARDs are allowed: oral or parenteral methotrexate ([MTX]; 7.5to 25 mg/week), sulfasalazine (≤ 3000 mg/day), hydroxychloroquine (≤ 400mg/day), chloroquine (≤ 250 mg/day), and leflunomide (≤ 20 mg/day).

2. A combination of up to 2 background csDMARDs is allowed, except the combinationof MTX and leflunomide.

• Meets all of the following disease activity criteria:

1. Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;

2. Level of high-sensitivity C-reactive protein ≥ 3 mg/L (by central laboratory);

3. Documented seropositivity for serum Rheumatoid Factor (RF) and/orAnti-citrullinated protein antibody (ACPA) (>ULN) at screening or by priorlaboratory evaluation.

• Has completed a locally approved authorized COVID-19 vaccine regimen according tolocal guidance at least 3 weeks before the first dose of the InvestigationalProduct.

• Must have discontinued all bDMARDs or JAKi prior to the first dose ofinvestigational product. The washout period for bDMARDs or JAKi prior to the firstdose of investigational product is specified below. For bDMARDs or JAKi not listedbelow washout should be at least 5 times the mean elimination half-life of a drug:

1. ≥ 4 weeks for etanercept;

2. ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept,tocilizumab, and sarilumab;

3. ≥ 1 year for rituximab;

4. ≥ 2 weeks for JAKi (either investigational or commercially availabletreatment).

• Voluntarily sign and date an informed consent form approved by independent ethicscommittee/Institutional Review Board (IRB)

Exclusion Criteria:

• Prior exposure to any other anti-CD40/CD40L agent.

• Inadequate response to 5 or more classes of advanced targeted therapies (bDMARD ortsDMARD; e.g., TNF inhibitors, IL-6 receptor inhibitors, T-cell costimulatoryinhibitors, anti-CD-20 antibodies, JAK inhibitors). This does not include priordiscontinuation due to drug intolerance.

• Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/daydose oral prednisone or equivalent within 8 weeks prior to randomization.

• History of any arthritis with onset prior to age 16 years or current diagnosis ofinflammatory joint disease other than RA (Current diagnosis of secondary Sjogren'ssyndrome is permitted).

• History of thromboembolic event or a significant risk of future thromboembolicevents

• Clinically significant active infection including signs/symptoms suggestive ofinfection, any significant recurrent or chronic infection, or subjects at a highrisk of infection

• History of cancer within the last 5 years from screening, except for basal andsquamous cell carcinoma of the skin or in situ carcinoma of the cervix treated andconsidered cured.

• History of any of the following cardiovascular conditions:

1. Moderate to severe congestive heart failure (New York Heart Association classIII or IV);

2. Recent (within past 6 months) cerebrovascular accident, myocardial infarction,coronary stenting;

3. Uncontrolled hypertension as defined by a confirmed systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg.

• Clinically relevant or significant electrocardiogram (ECG) abnormalities, includingECG with QT interval corrected for heart rate (QTc) > 500 msec.