Farletuzumab: A Comprehensive Analysis of a Folate Receptor Alpha-Targeted Therapy from Monoclonal Antibody to Antibody-Drug Conjugate

Executive Summary

Farletuzumab is an investigational biotech therapeutic that has undergone a significant strategic evolution, reflecting key advancements in the understanding of targeted cancer therapy. Initially developed as a humanized monoclonal antibody (mAb), Farletuzumab targets Folate Receptor Alpha (FRα), a cell surface protein highly overexpressed in various epithelial malignancies, most notably ovarian cancer, but with limited expression in normal tissues. This differential expression profile presented a compelling rationale for a tumor-selective therapy. Early clinical trials of Farletuzumab as a standalone agent or in combination with chemotherapy showed a favorable safety profile and preliminary signs of efficacy, generating considerable optimism.

However, the trajectory of Farletuzumab was profoundly altered by the results of a pivotal, large-scale Phase III clinical trial in patients with platinum-sensitive recurrent ovarian cancer. The study failed to meet its primary endpoint of improving progression-free survival in the overall patient population. This outcome led to a temporary halt in its clinical development and a re-evaluation of its therapeutic strategy. A critical turning point emerged from a prespecified, exploratory post-hoc analysis of the trial data, which revealed that a subset of patients with low baseline levels of the tumor antigen CA-125 experienced a statistically significant benefit in both progression-free and overall survival. This finding, supported by preclinical evidence, suggested that high levels of circulating CA-125 could interfere with the antibody's immune-mediated mechanism of action, providing a crucial insight into the complexities of the tumor microenvironment and the importance of refined biomarker-driven patient selection.

This deeper understanding, combined with Farletuzumab's demonstrated high specificity for FRα and its excellent safety profile, provided the foundation for its strategic rebirth. The molecule was repurposed as the targeting component of a next-generation therapeutic: the antibody-drug conjugate (ADC) Farletuzumab Ecteribulin (MORAb-202). In this construct, Farletuzumab serves as a highly specific delivery vehicle for the potent cytotoxic payload eribulin, aiming to enhance antitumor efficacy by concentrating the toxin directly within FRα-expressing cancer cells. Early clinical data for this ADC have shown renewed promise in difficult-to-treat patient populations, such as those with platinum-resistant ovarian cancer.

The corporate journey of Farletuzumab mirrors its scientific evolution. After initial development by Morphotek, Inc., an Eisai subsidiary, the ADC program attracted a major global strategic collaboration with Bristol Myers Squibb. The recent dissolution of this partnership has resulted in Eisai regaining full global rights, positioning Farletuzumab Ecteribulin as a high-priority, wholly-owned asset in its oncology pipeline. This report provides a comprehensive analysis of Farletuzumab, detailing its molecular characteristics, its complex clinical history, its strategic pivot to an ADC, and the corporate and regulatory landscape that has shaped its path.

Molecular Profile and Structural Characterization of Farletuzumab

Farletuzumab is a biologic therapeutic classified as a humanized monoclonal antibody, representing a sophisticated example of protein engineering designed for targeted oncology applications.[1] Its development and structural characteristics are central to understanding both its initial therapeutic rationale and its subsequent evolution into a component of an antibody-drug conjugate.

Classification and Origin

Farletuzumab (development code: MORAb-003) is a humanized monoclonal antibody of the Immunoglobulin G1 kappa (IgG1/κ) isotype.[2] It was developed by Morphotek, Inc., a subsidiary of Eisai, through the humanization of a murine (mouse-derived) antibody known as LK26.[5] The humanization process involved grafting the complementarity-determining regions (CDRs)—the specific parts of the antibody that recognize and bind to the target antigen—from the murine LK26 antibody into a human IgG1/κ backbone.[7] This technique is designed to retain the high binding affinity and specificity of the original murine antibody while minimizing the potential for an immunogenic response in human patients, a common limitation of non-humanized antibodies. The result is a molecule that is largely human in sequence, thereby improving its safety and pharmacokinetic profile for clinical use.[7]

The fundamental structure of Farletuzumab as a humanized IgG1 antibody is the source of both its initial therapeutic hypothesis and its ultimate utility as an ADC backbone. The IgG1 isotype was deliberately chosen for its potent ability to engage the host's immune system. This isotype is the most effective at mediating immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which formed the primary therapeutic rationale for the original drug.[1] However, pivotal clinical trials revealed that this immune-mediated effect was insufficient on its own to produce a significant clinical benefit in a broad patient population.[9] Despite this clinical setback, the molecule's high specificity for its target, a direct result of the grafted CDRs from the murine LK26 antibody, proved to be its most enduring and valuable asset. This high specificity, combined with a favorable safety profile consistently demonstrated in clinical trials, represents the ideal characteristics for a targeting vehicle in an ADC.[1] For an ADC, the primary goal is to deliver a potent toxin specifically to cancer cells while minimizing systemic exposure and off-target toxicity. Consequently, the very molecular features that defined Farletuzumab's initial, less successful therapeutic approach—specificity from its variable region and safety from its humanized framework—became the critical enablers for its strategic pivot. The molecule's value proposition effectively shifted from being an "effector" of the immune system to being a highly precise "delivery system" for a cytotoxic payload.[1]

Physicochemical Properties

Farletuzumab is a large biomolecule with well-defined physicochemical properties that dictate its behavior in biological systems.

• CAS Number: 896723-44-7 [3]
• Molecular Formula: $C_{6466}H_{9928}N_{1716}O_{2020}S_{42}$ [3]
• Molecular Weight: Approximately 145.4 kDa (a more precise molar mass is reported as 145371.06 g·mol⁻¹).[3] This large size is a key determinant of its pharmacokinetic properties, such as its confinement primarily to the vascular and interstitial compartments and its slow clearance from the body.

Amino Acid Sequence

The precise structure of Farletuzumab is defined by the amino acid sequences of its constituent heavy and light polypeptide chains. As a typical IgG antibody, it is composed of two identical heavy chains and two identical light chains, linked together by disulfide bonds.[2] The complete sequences, as registered in the U.S. Food and Drug Administration's Global Substance Registration System (GInAS), provide the definitive primary structure of the molecule.[2] This level of detail is critical for biopharmaceutical manufacturing, quality control, understanding structure-function relationships, predicting potential immunogenicity, and enabling the development of biosimilars.[1]

Heavy Chain Sequence (449 amino acids):

EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNTLFLQMDSLRATEDTGVYFCARHGDDPAWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 2

Light Chain Sequence (219 amino acids):

DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 2

The Folate Receptor Alpha (FRα) Target: A Strategic Therapeutic Window in Oncology

The therapeutic rationale for Farletuzumab is fundamentally rooted in the unique biological characteristics of its molecular target, Folate Receptor Alpha (FRα). The distinct expression pattern of FRα in malignant versus healthy tissues creates a highly attractive therapeutic window for targeted cancer therapies.

FRα Biology and Expression

FRα, encoded by the FOLR1 gene, is a 38-40 kDa glycosylphosphatidylinositol (GPI)-anchored cell-surface glycoprotein.[1] Its primary physiological function is to bind folate and its derivatives with high affinity (nanomolar range) and facilitate their transport into the cell via receptor-mediated endocytosis.[5] This process is crucial for providing the necessary folate cofactors for one-carbon metabolism, which is essential for the synthesis of nucleotides (DNA and RNA) and other critical metabolic processes.[4]

The core therapeutic premise for targeting FRα lies in its highly differential expression pattern. In normal adult tissues, FRα expression is severely restricted. It is found primarily on the apical (outward-facing) surfaces of a limited number of polarized epithelial cells, such as those in the kidney tubules, lungs, and choroid plexus.[1] In this configuration, the receptor is largely inaccessible to antibodies circulating in the bloodstream, effectively sequestering it from systemic therapeutic agents.[1]

In stark contrast, FRα is highly overexpressed in a wide range of epithelial-derived malignancies. It is present in approximately 90% of non-mucinous epithelial ovarian cancers (EOC) and is also frequently overexpressed in other cancers, including endometrial, triple-negative breast, and certain subtypes of non-small cell lung cancer (NSCLC), particularly adenocarcinomas.[1] In tumor cells, the protein is often distributed across the entire cell surface due to a loss of cellular polarity, making it readily accessible to circulating antibodies.[1] This dramatic overexpression on cancer cells, coupled with its restricted and sequestered expression in normal tissues, creates an ideal scenario for targeted therapy, offering the potential for potent, tumor-selective effects with a wide therapeutic index and limited off-target toxicity.[1]

Role in Oncogenesis

FRα is not merely a passive surface marker for tumor cells; it is functionally implicated in the process of oncogenesis. Its overexpression is positively correlated with higher tumor stage and grade, suggesting a role in tumor progression and aggressiveness.[4] Furthermore, FRα expression is maintained in metastatic lesions and recurrent tumors, making it a stable target throughout the course of the disease.[5] Preclinical studies have shown that cells engineered to overexpress FRα gain a significant growth advantage, particularly in low-folate conditions, and that down-regulating FRα expression can inhibit cancer cell proliferation.[5] This indicates that FRα plays an active role in sustaining the high metabolic and proliferative demands of cancer cells, solidifying its status as a functional therapeutic target rather than just a biomarker for drug delivery.[5]

The clinical journey of Farletuzumab, however, reveals that while the high expression of FRα on tumor cells makes it an excellent theoretical target, simple target expression is not a sufficient predictor of therapeutic success. The initial premise was straightforward: since FRα is overexpressed on ovarian tumors, an anti-FRα antibody should be effective.[1] Yet, the pivotal Phase III trial, which enrolled a broad population of patients with platinum-sensitive ovarian cancer—a group known for high FRα expression—failed to meet its primary endpoint.[9] This outcome directly challenged the simple "target-present, drug-works" hypothesis. The crucial missing piece of the puzzle was provided by the post-hoc analysis, which demonstrated that only patients with low levels of the circulating tumor antigen CA-125 derived a significant benefit from the therapy.[10] This finding suggested that a co-factor in the tumor microenvironment, CA-125, could effectively abrogate the drug's immune-mediated mechanism of action, even when the primary target, FRα, was present. This insight forced a fundamental re-evaluation of patient selection strategies for FRα-targeted therapies. It established that the biological context is paramount and that successful targeting depends not just on if the target is present, but also on the conditions under which it can be effectively engaged. This knowledge, derived from the Farletuzumab trials, has been instrumental in advancing the entire field of FRα-targeted therapy, influencing the development and biomarker strategies for subsequent agents, including the now-approved ADC, mirvetuximab soravtansine.[1]

Multifaceted Mechanism of Action (MoA)

Farletuzumab was designed to elicit antitumor effects through several distinct biological mechanisms, primarily by leveraging the host immune system and interfering with tumor cell signaling pathways. The multifaceted nature of its proposed mechanism of action reflects a comprehensive approach to targeting FRα-positive cancer cells.

Immune Effector Functions

The IgG1 backbone of Farletuzumab was specifically chosen for its ability to potently engage immune effector pathways, a primary intended mechanism of tumor cell killing.[1]

• Antibody-Dependent Cellular Cytotoxicity (ADCC): This is a primary proposed pathway for Farletuzumab's activity. Upon binding to FRα on the surface of a tumor cell, the constant (Fc) region of the Farletuzumab antibody becomes accessible to Fc-gamma receptors (FcγR) expressed on the surface of immune effector cells, most notably Natural Killer (NK) cells.[1] This cross-linking event activates the NK cell, triggering the release of cytotoxic granules containing perforin and granzymes, which induce apoptosis in the targeted tumor cell. Preclinical studies confirmed that Farletuzumab could mediate robust ADCC against FRα-expressing human ovarian cancer cell lines.[1]
• Complement-Dependent Cytotoxicity (CDC): In parallel, the Fc region of Farletuzumab, when bound to the tumor cell, can also activate the classical complement pathway. This is initiated by the binding of the C1q protein to the antibody, which triggers a proteolytic cascade involving numerous complement proteins.[1] The culmination of this cascade is the formation of the Membrane Attack Complex (MAC), a pore-like structure that inserts into the tumor cell membrane, disrupting osmotic balance and leading to cell lysis. In vitro studies demonstrated that Farletuzumab could elicit CDC, although the effect was noted to be dependent on the cellular context.[1]

Signaling Pathway Inhibition

Beyond its immune-mediated effects, Farletuzumab has been shown to directly interfere with pro-survival signaling pathways associated with FRα. Preclinical investigations revealed that Farletuzumab binding can inhibit the interaction between FRα and Lyn kinase, a non-receptor cytoplasmic tyrosine kinase belonging to the Src family.[3] This interaction is believed to be part of a signaling complex that confers a growth advantage to FRα-expressing cells. By disrupting this association, Farletuzumab can block downstream signaling, thereby reducing tumor cell proliferation.[4]

Induction of Autophagy

Further preclinical research has identified another distinct mechanism of action: the induction of autophagy-associated cell death. Studies using three-dimensional in vitro models showed that Farletuzumab treatment could inhibit tumor growth by triggering autophagy, a cellular process of self-degradation.[3] This effect was observed as a reduction in tumor cell proliferation, but notably, it did not appear to involve a significant induction of apoptosis, suggesting a separate and distinct cell death pathway.[4]

Distinction from Antifolate Drugs

It is critical to distinguish Farletuzumab's mechanism of action from that of antifolate chemotherapies (e.g., pemetrexed, methotrexate). Farletuzumab binds to an epitope on the FRα protein that is distinct from the folate-binding site.[20] Consequently, in vitro studies have demonstrated that Farletuzumab does not block the binding of folic acid or various antifolate drugs to the receptor.[4] Furthermore, it has a minimal effect on the cytoplasmic accumulation or cellular uptake of folates via FRα-mediated transport and does not alter the cytotoxic potency of antifolates.[20] This key distinction means that its mechanism is not based on starving the cell of essential metabolites. It also implies that the concomitant use of Farletuzumab with antifolate chemotherapies is not contraindicated, as their mechanisms of action are non-competitive and complementary.[20]

Pharmacological and Preclinical Profile

A comprehensive evaluation of Farletuzumab's pharmacological properties and preclinical performance established a strong foundation for its clinical development, demonstrating predictable pharmacokinetics, in vivo antitumor activity, and a favorable safety profile.

Pharmacokinetics (PK)

Population pharmacokinetic analyses, conducted using data from clinical trials in patients with advanced ovarian cancer, have provided a detailed characterization of Farletuzumab's behavior in the human body.[25]

• Pharmacokinetic Model: The pharmacokinetic profile of Farletuzumab was best described by a two-compartment model with first-order (linear) elimination across the clinically relevant dose range.[25] This model indicates that the drug distributes from a central compartment (primarily the bloodstream) into a peripheral compartment (tissues) before being eliminated from the body.
• Distribution: The estimated volume of distribution for the central compartment ($V_c$) was 3.00 L, which is consistent with the plasma volume, and the volume for the peripheral compartment ($V_p$) was 7.50 L.[25] The relatively small total volume of distribution is characteristic of large monoclonal antibodies, reflecting their limited penetration into tissues due to their size and hydrophilic nature.[25]
• Clearance and Half-Life: Farletuzumab exhibited slow clearance from the body, with an estimated clearance (CL) value of 0.00784 L/h (or 0.188 L/day), a rate comparable to other therapeutic monoclonal antibodies.[25] This slow clearance contributes to a long half-life. The model calculated a distribution half-life (alpha) of 2.48 days and a terminal elimination half-life (beta) of 49.2 days.[25] The effective or functional half-life, which accounts for drug accumulation with repeated dosing, was calculated to be approximately 12.5 days, supporting weekly or three-weekly intravenous administration schedules.[25]
• Covariate Analysis: A thorough analysis of patient characteristics (covariates) found that body weight was the only factor that significantly explained inter-patient variability in clearance and central volume of distribution.[25] This finding provides a strong rationale for the use of weight-based dosing to ensure more consistent drug exposure across patients. Other factors, including patient age, the presence of human anti-human antibodies (HAHA), and concomitant chemotherapy, were found to have no significant effect on Farletuzumab's pharmacokinetics.[25]

The key pharmacokinetic parameters are summarized in Table 1. These parameters are crucial for designing optimal dosing regimens that maintain therapeutic drug concentrations while minimizing potential toxicity.

Table 1: Summary of Key Pharmacokinetic Parameters of Farletuzumab

Parameter	Estimated Value	Unit
Clearance (CL)	0.00784	L/h
Central Volume of Distribution ($V_c$)	3.00	L
Peripheral Volume of Distribution ($V_p$)	7.50	L
Inter-compartmental Clearance (Q)	0.0203	L/h
Distribution Half-life ($t_{1/2, \alpha}$)	2.48	days
Elimination Half-life ($t_{1/2, \beta}$)	49.2	days
Effective Half-life ($t_{1/2, eff}$)	~12.5	days
Data derived from population pharmacokinetic modeling in patients with epithelial ovarian cancer.25

Preclinical Safety and Efficacy

Extensive preclinical studies were conducted to evaluate the antitumor activity and safety of Farletuzumab before it entered human trials.

• In Vivo Efficacy: The antitumor potential of Farletuzumab was demonstrated in well-characterized xenograft models of human ovarian cancer. In these studies, nude mice bearing human ovarian tumor xenografts (e.g., SK-OV-3) and treated with Farletuzumab or its murine precursor, LK26, showed a significant reduction in tumor growth compared to control animals.[5] Notably, the greatest efficacy was observed when Farletuzumab was administered in combination with the chemotherapeutic agent docetaxel, which resulted in near-complete tumor growth inhibition, suggesting a synergistic relationship.[6]
• Toxicology and Safety: Non-human primate studies are a critical component of preclinical safety assessment for biologics. Farletuzumab was evaluated in cynomolgus monkeys, which were identified as a relevant toxicological model due to similar tissue binding profiles of the antibody in human and monkey tissues.[5] These studies, including repeat-dose toxicology studies lasting up to 24 weeks, demonstrated a favorable safety profile with no significant toxicities observed.[5]
• Reproductive Toxicology: In a dedicated embryo-fetal development study, pregnant cynomolgus monkeys were administered high doses of Farletuzumab during the critical period of organogenesis.[26] The results showed no evidence of teratogenicity or any other Farletuzumab-related adverse effects on maternal animals or developing fetuses.[27] This important finding, supported by the fact that the antibody does not interfere with cellular folate uptake, suggests a low risk of fetal harm, a rare and favorable characteristic for an oncology drug.[20]

The Clinical Odyssey of Farletuzumab as a Monoclonal Antibody

The clinical development of Farletuzumab as a standalone monoclonal antibody was a journey of initial promise followed by a significant setback, which ultimately yielded invaluable scientific insights that reshaped the field of FRα-targeted therapy.

Early Phase Trials (Phase I/II): Establishing a Foundation

The clinical investigation of Farletuzumab began with early-phase trials designed to assess its safety, pharmacokinetics, and preliminary antitumor activity. A key Phase I dose-escalation study (MORAb-003-001) enrolled 25 heavily pretreated patients with platinum-refractory or platinum-resistant epithelial ovarian cancer, a population with limited treatment options.[12] The study's findings were highly encouraging and formed the basis for further development.

The trial demonstrated that weekly intravenous infusions of Farletuzumab were generally safe and well-tolerated across a wide dose range, from 12.5 to 400 mg/m².[12] Crucially, no dose-limiting toxicities (DLTs) were encountered, and therefore, a maximum tolerated dose (MTD) was not established, indicating a very favorable safety window.[12] Pharmacokinetic analysis showed dose-proportional increases in drug exposure, and a nuclear imaging substudy confirmed that the antibody successfully targeted and localized to tumor sites.[12]

While the study was not designed to definitively measure efficacy, it provided promising early signals of clinical activity. Among this difficult-to-treat population, 36% of patients (9 of 25) achieved stable disease as their best response.[12] Furthermore, four patients experienced a reduction in their serum CA-125 levels, a key biomarker for ovarian cancer burden.[12] These positive early results, demonstrating both safety and biological activity, generated significant enthusiasm and provided a strong rationale to advance Farletuzumab into larger, more definitive clinical trials.[1]

The Pivotal Phase III Trial (MORAb-003-004 / FAR 131): A Major Setback

Building on the promising early data, Eisai launched a large-scale, global Phase III trial to definitively evaluate the efficacy of Farletuzumab. The study, known as MORAb-003-004 or FAR 131, was a randomized, double-blind, placebo-controlled trial that enrolled 1,100 women with platinum-sensitive epithelial ovarian cancer experiencing their first relapse.[9]

• Study Design: Patients were randomized in a 1:1:1 ratio to receive standard-of-care chemotherapy (six cycles of carboplatin plus a taxane, either paclitaxel or docetaxel) in combination with either placebo, a low dose of Farletuzumab (1.25 mg/kg weekly), or a high dose of Farletuzumab (2.5 mg/kg weekly). After the combination phase, patients continued to receive their assigned agent (Farletuzumab or placebo) as a single-agent maintenance therapy until disease progression.[10]
• Primary Endpoint Failure: The primary endpoint of the study was progression-free survival (PFS). The preliminary results, announced in 2013, and the final published analysis revealed that the trial did not meet this primary endpoint.[1] The median PFS was 9.0 months in the placebo group, 9.5 months in the low-dose Farletuzumab group, and 9.7 months in the high-dose Farletuzumab group. Neither of the Farletuzumab arms demonstrated a statistically significant improvement in PFS compared to the placebo arm.[10] This outcome was a major setback for the program and led to the discontinuation of certain clinical development pathways for Farletuzumab as a standalone therapy.[1]

Post-Hoc Revelations and the CA-125 Hypothesis

While the primary analysis of the FAR 131 trial was negative, the story of Farletuzumab did not end there. A prespecified, exploratory analysis included in the final statistical plan provided a critical and field-altering insight.[10]

• The Subgroup Finding: This analysis examined patient outcomes based on their baseline serum CA-125 levels. It revealed a striking and statistically significant interaction. In the subgroup of patients who had a low baseline CA-125 level (defined as less than or equal to three times the upper limit of normal, or ≤3x ULN), treatment with the higher dose of Farletuzumab (2.5 mg/kg) resulted in a dramatic improvement in clinical outcomes compared to placebo.[10]
• Progression-Free Survival (PFS): The hazard ratio (HR) was 0.49, indicating a 51% reduction in the risk of progression or death ($p =.0028$).[10]
• Overall Survival (OS): The hazard ratio (HR) was 0.44, indicating a 56% reduction in the risk of death ($p =.0108$).[10]
• The Mechanistic Link: This powerful clinical observation was supported by preclinical data suggesting a direct biological mechanism. It was hypothesized and later shown that high concentrations of circulating CA-125, a large glycoprotein shed by ovarian cancer cells, could directly bind to Farletuzumab and inhibit its ability to mediate ADCC by suppressing the function of NK cells.[10] This provided a compelling biological explanation for why the drug was effective only in patients with low levels of this interfering antigen.
• Strategic Impact: This discovery was pivotal. It transformed the understanding of Farletuzumab's activity, suggesting that CA-125 was not merely a biomarker of disease burden but also a predictive biomarker of therapeutic resistance. This insight directly informed subsequent clinical strategy, leading to the initiation of a new Phase II study (MORAb-003-011) designed specifically to test Farletuzumab plus chemotherapy in the prospectively selected population of platinum-sensitive ovarian cancer patients with low CA-125 levels.[31] Although this follow-up study also did not show a significant benefit over placebo/chemotherapy, the initial finding from the Phase III trial fundamentally advanced the understanding of FRα-targeted immunotherapy and underscored the critical importance of sophisticated biomarker strategies that account for inhibitory factors within the tumor microenvironment.[1]

Explorations in Other Malignancies

Beyond ovarian cancer, Farletuzumab was also investigated in other FRα-expressing solid tumors. A notable example is the FLAIR study (NCT01218516), a randomized, double-blind, placebo-controlled Phase II trial that evaluated Farletuzumab in combination with platinum-based chemotherapy in chemotherapy-naive patients with Stage IV adenocarcinoma of the lung.[34] This and other explorations provided a more complete picture of its investigational history across different cancer types.

Comprehensive Safety and Tolerability Assessment

A thorough evaluation of Farletuzumab's safety profile across its extensive clinical trial program, particularly the large Phase III FAR 131 study, has consistently demonstrated that the antibody is well-tolerated and adds minimal toxicity when combined with standard chemotherapy regimens.

Overall Safety Profile

The comprehensive safety analysis from the 1,100-patient Phase III trial showed that the overall incidence and types of adverse events were comparable across the placebo and the two Farletuzumab dose groups.[10] The addition of Farletuzumab to a standard carboplatin and taxane backbone did not result in new or unexpected safety signals.[10] This favorable safety profile is a crucial attribute, especially for a drug being considered for combination therapy or as a backbone for an ADC, where minimizing additive toxicity is paramount.[1]

Common Adverse Events

The most frequently reported treatment-emergent adverse events (TEAEs) were those already well-known to be associated with the background chemotherapy agents.[9] A meta-analysis of seven prospective studies confirmed that the most common AEs were gastrointestinal and hematological in nature.[22] Key TEAEs reported in the pivotal Phase III study are detailed in Table 2.

Table 2: Incidence of Common Treatment-Emergent Adverse Events (≥25%) in the MORAb-003-004 Phase III Trial

MedDRA Preferred Term	Placebo + Chemo (n=352)	Farletuzumab 1.25 mg/kg + Chemo (n=376)	Farletuzumab 2.5 mg/kg + Chemo (n=363)
Alopecia	57.4%	58.8%	50.7%
Nausea	54.3%	58.0%	51.2%
Neutropenia	51.4%	58.5%	52.3%
Fatigue	42.9%	46.0%	37.5%
Anemia	35.8%	38.6%	43.5%
Diarrhea	36.4%	36.4%	35.8%
Thrombocytopenia	29.0%	34.6%	33.6%
Vomiting	30.4%	35.1%	31.1%
Constipation	29.3%	32.2%	29.5%
Abdominal pain	27.0%	29.0%	25.1%
Data adapted from the Phase III study publication.10 Percentages represent the proportion of patients in each arm experiencing the event at any grade.

As shown in the table, the incidence of most common AEs was broadly similar across all three arms. A slight increase in anemia was noted in the higher-dose Farletuzumab group, but overall, the data support the conclusion that Farletuzumab did not significantly exacerbate the toxicity of standard chemotherapy.[10] Other common adverse effects noted across studies include hypersensitivity reactions, pyrexia (fever), chills, and headache.[3]

Serious Adverse Events (SAEs) and Events of Special Interest

The rates of serious adverse events were also generally similar between treatment groups. However, in a separate Phase II study (MORAb-003-011) evaluating Farletuzumab in a low CA-125 population, a higher incidence of interstitial lung disease (ILD) was reported in the Farletuzumab/chemotherapy arm (5%, or 7 of 141 patients) compared to the placebo/chemotherapy arm (0%).[31] While most of these events were low-grade (Grade 1 or 2), two were Grade 3 in severity.[31] This finding highlights ILD as a potential adverse event of special interest that requires careful monitoring in patients receiving Farletuzumab-based therapies, including the ADC form.

Rebirth as an Antibody-Drug Conjugate: Farletuzumab Ecteribulin (MORAb-202)

The clinical journey of Farletuzumab as a standalone antibody, while not leading to regulatory approval, provided the ideal foundation for its strategic reinvention as a key component of a next-generation therapeutic: an antibody-drug conjugate (ADC). This pivot leverages the antibody's greatest strengths while addressing its primary limitation.

Rationale and Molecular Construct

The rationale for developing an ADC based on Farletuzumab was born directly from the results of its clinical program. While the monoclonal antibody itself failed to demonstrate sufficient potency to achieve its primary endpoints in broad patient populations, it consistently proved to have two highly desirable characteristics: high target specificity for FRα and a favorable safety profile.[1] These are the quintessential attributes of an ideal targeting moiety for an ADC. The strategic goal was to enhance therapeutic efficacy by using Farletuzumab as a "guided missile" to deliver a highly potent cytotoxic agent directly to FRα-expressing cancer cells, thereby maximizing on-target killing while minimizing systemic toxicity.[1]

The resulting ADC is Farletuzumab Ecteribulin (development code: MORAb-202; also referred to as FZEC). Its molecular construct consists of three key components [13]:

1. The Antibody: Farletuzumab, the humanized IgG1 anti-FRα monoclonal antibody, serves as the targeting vehicle.
2. The Payload: Eribulin (brand name Halaven®), a potent microtubule dynamics inhibitor developed in-house by Eisai. Eribulin functions by inhibiting the growth phase of microtubules, which prevents cell division and leads to apoptotic cell death.[37]
3. The Linker: A cathepsin-B cleavable linker connects eribulin to the farletuzumab antibody. This linker is designed to be stable in the bloodstream but is cleaved by enzymes (like cathepsin-B) that are often present at high levels inside cancer cells, ensuring the release of the cytotoxic payload primarily at the intended site of action.[22]

A key feature of this construct, demonstrated in preclinical studies, is its ability to elicit a "bystander effect".[37] Once the eribulin payload is released inside the target FRα-positive cancer cell, it is cell-permeable and can diffuse into the surrounding tumor microenvironment, killing adjacent FRα-negative cancer cells. This mechanism has the potential to overcome tumor heterogeneity—a common cause of resistance to targeted therapies—by expanding the therapeutic effect beyond only the cells that express the target antigen.[37]

Clinical Evaluation and Renewed Promise

The clinical development of Farletuzumab Ecteribulin has shown encouraging early results, reigniting interest in the Farletuzumab molecule and the FRα target.

• Early Phase Data: The dose-expansion portion of the Phase 1 Study 101 (NCT03386942), conducted in Japan, provided the first clinical proof-of-concept for the ADC.[37] In a cohort of patients with heavily pretreated, platinum-resistant ovarian cancer, Farletuzumab Ecteribulin demonstrated notable antitumor activity. At the 0.9 mg/kg dose, the overall response rate (ORR) was 25.0%, and the disease control rate (DCR) was 66.7%.[37] At a higher dose of 1.2 mg/kg, the ORR was even more impressive at 52.4%.[42] These response rates are clinically meaningful in this difficult-to-treat patient population and compare favorably to existing therapies. The safety profile was deemed manageable, with the most common TEAEs being bone marrow suppression (neutropenia, anemia), nausea, and pyrexia.[37]
• Ongoing Clinical Trials: Based on these promising results, a global clinical development program for Farletuzumab Ecteribulin is underway. An overview of key ongoing or recently completed trials is provided in Table 3. These studies are investigating the ADC in various FRα-positive solid tumors, including ovarian, endometrial, and non-small cell lung cancer, and are exploring different dosing regimens and combinations.[38]

Table 3: Overview of Key Clinical Trials for Farletuzumab Ecteribulin (MORAb-202)

NCT Identifier	Phase	Title / Indication	Status (as of late 2022/early 2023)	Primary Objectives
NCT03386942	Phase 1	Study of MORAb-202 in Participants With Solid Tumors	Completed	Evaluate safety, tolerability, and determine the recommended dose.
NCT04300556	Phase 1/2	Study of MORAb-202 in Participants With Selected Tumor Types (Ovarian, Endometrial, NSCLC)	Active, Recruiting	Evaluate safety, tolerability, and efficacy; determine recommended Phase 2 dose (RP2D).
NCT05613088	Phase 2	Study of MORAb-202 Versus Investigator's Choice Chemotherapy in Platinum-Resistant Ovarian Cancer	Completed	Assess safety, tolerability, and efficacy of MORAb-202 compared to standard chemotherapy.
NCT05577715	Phase 2	Study of MORAb-202 in Metastatic NSCLC Adenocarcinoma	Terminated	Assess safety, tolerability, and efficacy of MORAb-202 in NSCLC.
Trial information sourced from ClinicalTrials.gov.38

These trials represent the current frontier for the Farletuzumab molecule, aiming to validate the ADC concept and potentially deliver a new therapeutic option for patients with high unmet medical needs.

Corporate Strategy and Regulatory Landscape

The development trajectory of Farletuzumab is deeply intertwined with a dynamic corporate history of innovation, strategic partnerships, and portfolio realignments. This corporate narrative provides a tangible reflection of the evolving scientific understanding and perceived commercial viability of the asset at each stage of its lifecycle.

A History of Development and Collaboration

• Morphotek and Eisai Era: Farletuzumab (MORAb-003) was originally developed by Morphotek, Inc., a clinical-stage biotechnology company that was later acquired by and became a subsidiary of the Japanese pharmaceutical company Eisai Inc..[3] Under Eisai's stewardship, Farletuzumab was advanced through its extensive clinical program as a monoclonal antibody, including the pivotal but ultimately unsuccessful Phase III trial.[5]
• The Bristol Myers Squibb Partnership: Following the strategic pivot to the ADC form, Farletuzumab Ecteribulin (MORAb-202), the program's potential attracted significant interest. In June 2021, Eisai entered into a major exclusive global strategic collaboration with Bristol Myers Squibb (BMS) for the co-development and co-commercialization of the ADC.[39] The financial terms of this agreement were substantial and underscored the high value placed on the asset. BMS made an upfront payment to Eisai of $650 million, which included $200 million earmarked for R&D expenses. The deal also included the potential for up to $2.45 billion in future development, regulatory, and commercial milestone payments.[39] This blockbuster partnership provided a massive external validation of the MORAb-202 program and its potential to become a best-in-class FRα-targeted ADC.
• Partnership Dissolution and Eisai's Solo Path: In a significant strategic shift, the collaboration was terminated in July 2024.[22] BMS's decision to exit the partnership was attributed to its "ongoing portfolio prioritization efforts" as part of a broader corporate initiative to achieve cost savings.[48] Following the termination, Eisai regained full, exclusive global rights to Farletuzumab Ecteribulin. As part of the agreement, Eisai will refund the unused portion of the $200 million R&D payment to BMS.[38] Immediately upon regaining the rights, Eisai announced that it would accelerate the global development and commercialization of the ADC, designating it as a high-priority asset within its oncology pipeline.[38] This sequence of events—from internal innovation to a major partnership and now to a focused solo development effort—suggests that while BMS's strategic priorities have shifted, Eisai's internal assessment of the ADC's scientific data and commercial potential remains highly positive.

Global Regulatory Status

Despite its long development history, Farletuzumab and its ADC form remain investigational products and have not received marketing approval from any major regulatory agency. However, they have been granted special designations that facilitate their development.

• U.S. Food and Drug Administration (FDA): On June 16, 2006, Farletuzumab was granted Orphan Drug Designation by the FDA for the treatment of ovarian cancer.[50] This designation is intended to encourage the development of drugs for rare diseases and provides benefits such as tax credits and potential market exclusivity upon approval. It is important to note that Farletuzumab is not FDA approved for this or any other indication.[50]
• European Medicines Agency (EMA): In April 2008, the European Commission granted Farletuzumab Orphan Medicinal Product Status for the treatment of ovarian cancer.[51] Similar to the FDA designation, this status provides incentives for development, including scientific advice and 10 years of market exclusivity in the European Union following a potential marketing authorization. The drug is not currently authorized for use in the EU.[51]
• Therapeutic Goods Administration (TGA), Australia: A review of publicly available information indicates that Farletuzumab and Farletuzumab Ecteribulin do not currently have any specific regulatory filings, designations, or approvals with the Australian TGA.[52] Their status in Australia remains investigational, likely within the framework of clinical trials.

Synthesis and Future Perspective

The story of Farletuzumab is a compelling case study in the iterative and often unpredictable nature of drug development. Its journey from a promising monoclonal antibody to the targeting component of a next-generation ADC encapsulates key lessons in oncology research, biomarker strategy, and corporate resilience. While the original Farletuzumab monoclonal antibody program failed to achieve its primary clinical objectives, it was far from a scientific or strategic failure. Instead, its legacy is threefold and has had a lasting impact on its field.

First, the extensive preclinical and clinical investigation of Farletuzumab was instrumental in validating Folate Receptor Alpha as a legitimate and viable therapeutic target in human cancers. The program confirmed that FRα's differential expression could be exploited to target tumors with a high degree of specificity and a favorable safety profile.

Second, and perhaps most importantly, the failure of the pivotal Phase III trial yielded invaluable, field-altering insights into biomarker strategy. The discovery of the interaction between Farletuzumab and CA-125 was a landmark finding. It demonstrated with robust clinical data that the efficacy of an immune-mediated therapy can be profoundly influenced by inhibitory factors within the tumor microenvironment. This shifted the paradigm for FRα-targeted therapies from a simple "target-present" model to a more nuanced understanding that requires consideration of the broader biological context, a lesson that has informed the development of all subsequent agents in this class.

Third, the original molecule served as the perfect foundation for a next-generation therapeutic. The strategic pivot to create the antibody-drug conjugate Farletuzumab Ecteribulin was a logical and scientifically sound evolution. This move leveraged the antibody's established strengths—its high specificity and excellent safety profile—while directly addressing its primary weakness: insufficient standalone potency. By arming Farletuzumab with the potent cytotoxic payload eribulin, Eisai has created a new therapeutic entity with a renewed and potentially much greater clinical promise.

Looking forward, the future of the Farletuzumab molecule is inextricably linked to the success of its ADC form, Farletuzumab Ecteribulin. The early clinical data in platinum-resistant ovarian cancer are encouraging and suggest that the ADC can induce meaningful responses in a patient population with high unmet need. However, it enters an increasingly competitive landscape. The field of FRα-targeted ADCs is now clinically validated, with the FDA's accelerated approval of mirvetuximab soravtansine for FRα-positive, platinum-resistant ovarian cancer setting a new benchmark.[22]

The ultimate success of Farletuzumab Ecteribulin will depend on several factors. It must demonstrate a competitive, if not superior, efficacy and safety profile in its ongoing and future clinical trials. Key differentiators, such as the potential of its "bystander effect" to overcome tumor heterogeneity, will need to be substantiated with robust clinical data. Finally, with the dissolution of the Bristol Myers Squibb partnership, the onus is now entirely on Eisai to navigate the complex clinical, regulatory, and commercial path forward. The journey of Farletuzumab is a testament to scientific perseverance, demonstrating how clinical setbacks can yield critical knowledge that paves the way for more sophisticated and potentially more effective therapeutic strategies.

Works cited

1. Farletuzumab: Advancing Antibody-Drug Conjugate Research in Ovarian Cancer, accessed October 28, 2025, https://www.assaygenie.com/blog/farletuzumab-advancing-antibody-drug-conjugate-research-in-ovarian-cancer/
2. FARLETUZUMAB - precisionFDA, accessed October 28, 2025, https://precision.fda.gov/ginas/app/ui/substances/a6328685-86e7-48b3-a8d3-b877a3730f1a
3. Farletuzumab - Wikipedia, accessed October 28, 2025, https://en.wikipedia.org/wiki/Farletuzumab
4. Profile of farletuzumab and its potential in the treatment of solid ..., accessed October 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4789847/
5. Role of Farletuzumab in Epithelial Ovarian Carcinoma - PMC - NIH, accessed October 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3576870/
6. Farletuzumab, accessed October 28, 2025, https://access.portico.org/Portico/show?viewFile=pdf&auId=pjbf78xdjf3
7. Farletuzumab Overview - Creative Biolabs, accessed October 28, 2025, https://www.creativebiolabs.net/farletuzumab-overview.htm
8. pmc.ncbi.nlm.nih.gov, accessed October 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4789847/#:~:text=The%20proposed%20mechanism%20of%20farletuzumab,and%20antibody%2Ddependent%20cellular%20cytotoxicity.
9. EISAI ANNOUNCES RESULTS OF PHASE Ⅲ STUDY OF ANTICANCER AGENT FARLETUZUMAB IN PATIENTS WITH RELAPSED PLATINUM-SENSITIVE OVARIAN CANCER | News Release：2013, accessed October 28, 2025, https://www.eisai.com/news/news201305.html
10. A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to ..., accessed October 28, 2025, https://ascopubs.org/doi/10.1200/JCO.2015.63.2596
11. A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse - PubMed, accessed October 28, 2025, https://pubmed.ncbi.nlm.nih.gov/27001568/
12. Farletuzumab, a Humanized Monoclonal Antibody against Folate ..., accessed October 28, 2025, https://aacrjournals.org/clincancerres/article/16/21/5288/14330/Farletuzumab-a-Humanized-Monoclonal-Antibody
13. MORAb-202, an Antibody–Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eri, accessed October 28, 2025, https://aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-17-1215/1915017/1535-7163_mct-17-1215v2.pdf
14. STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE, accessed October 28, 2025, https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/farletuzumab.pdf
15. Farletuzumab (MORAb-003) | FRα Inhibitor - MedchemExpress.com, accessed October 28, 2025, https://www.medchemexpress.com/farletuzumab.html
16. Farletuzumab (Anti-FOLR1) | Read Reviews & Product Use Citations - Selleck Chemicals, accessed October 28, 2025, https://www.selleckchem.com/products/farletuzumab-anti-folr1.html
17. Definition of farletuzumab - NCI Drug Dictionary - National Cancer Institute, accessed October 28, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/farletuzumab
18. FARLETUZUMAB - precisionFDA, accessed October 28, 2025, https://precision.fda.gov/ginas/app/ui/substances/2O09BG0OWA
19. FOLR1 - Folate receptor alpha - Homo sapiens (Human) | UniProtKB | UniProt, accessed October 28, 2025, https://www.uniprot.org/uniprotkb/P15328/entry
20. Farletuzumab, an anti-folate receptor α antibody, does not block binding of folate or anti-folates to receptor nor does it alter the potency of anti-folates in vitro - PubMed, accessed October 28, 2025, https://pubmed.ncbi.nlm.nih.gov/22644798/
21. A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse - ASCO Publications, accessed October 28, 2025, https://ascopubs.org/doi/abs/10.1200/JCO.2015.63.2596
22. Farletuzumab - Drug Targets, Indications, Patents - Patsnap Synapse, accessed October 28, 2025, https://synapse.patsnap.com/drug/cb9146d1030b438682e46f062af73b70
23. A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of farletuzumab (MORAb-003) in combination with weekly paclitaxel in subjects with platinum-resistant or refractory relapsed ovarian cancer. | Journal of Clinical Oncology - ASCO Publications, accessed October 28, 2025, https://ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.tps255
24. Full article: Profile of farletuzumab and its potential in the treatment of solid tumors, accessed October 28, 2025, https://www.tandfonline.com/doi/full/10.2147/OTT.S98242
25. Population pharmacokinetics of farletuzumab, a humanized ..., accessed October 28, 2025, https://www.springermedizin.de/population-pharmacokinetics-of-farletuzumab-a-humanized-monoclon/8292586
26. pubmed.ncbi.nlm.nih.gov, accessed October 28, 2025, https://pubmed.ncbi.nlm.nih.gov/29928988/#:~:text=Abstract,any%20embryonic%20or%20fetal%20abnormalities.
27. Farletuzumab, a monoclonal antibody directed against folate receptor alpha, shows no evidence of teratogenicity in cynomolgus monkeys - PubMed, accessed October 28, 2025, https://pubmed.ncbi.nlm.nih.gov/29928988/
28. Farletuzumab, a Humanized Monoclonal Antibody against Folate Receptor Alpha, in Epithelial Ovarian Cancer: A Phase I Study - AACR Journals, accessed October 28, 2025, https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-10-0700/83499/am/Farletuzumab-a-Humanized-Monoclonal-Antibody
29. Morphotek®, Inc. Announces an Agreement With Fujirebio Diagnostics, Inc to commercialize the CA125 II Assay as a Companion Diagnostic for Farletuzumab, accessed October 28, 2025, https://www.fujirebio.com/en-us/news-events/morphotekr-inc-announces-an-agreement-with-fujirebio-diagnostics-inc-to-commercialize
30. Morphotek®, Inc. Announces an Agreement With Fujirebio Diagnostics, Inc to commercialize the CA125 II Assay as a Companion Diagnostic for Farletuzumab, accessed October 28, 2025, https://www.fujirebio.com/en/news-events/morphotekr-inc-announces-an-agreement-with-fujirebio-diagnostics-inc-to-commercialize
31. Phase 2 Placebo-Controlled Study to Assess the Efficacy/Safety of Farletuzumab plus Chemotherapy in Women with Low CA-125 Platinum-Sensitive Ovarian Cancer - Journal of Oncology Navigation & Survivorship, accessed October 28, 2025, https://jons-online.com/special-issues-and-supplements/2021/2021-year-in-review-ovarian-cancer/phase-2-placebo-controlled-study-to-assess-the-efficacy-safety-of-farletuzumab-plus-chemotherapy-in-women-with-low-ca-125-platinum-sensitive-ovarian-cancer
32. Morphotek and Univeristy of Gothenburg to develop farletuzumab - Drug Target Review, accessed October 28, 2025, https://www.drugtargetreview.com/news/7843/morphotek-and-univeristy-of-gothenburg-to-develop-farletuzumab/
33. Morphotek and Eurofarma Laboratórios S.A. Sign Exclusive Licensing Agreement for Farletuzumab in Latin America - PR Newswire, accessed October 28, 2025, https://www.prnewswire.com/news-releases/morphotek-and-eurofarma-laboratorios-sa-sign-exclusive-licensing-agreement-for-farletuzumab-in-latin-america-300337215.html
34. Farletuzumab Completed Phase 2 Trials for Adenocarcinoma of the Lung Treatment, accessed October 28, 2025, https://go.drugbank.com/drugs/DB05595/clinical_trials?conditions=DBCOND0028475&phase=2&purpose=treatment&status=completed
35. NCT01218516 | A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung | ClinicalTrials.gov, accessed October 28, 2025, https://clinicaltrials.gov/study/NCT01218516
36. Efficacy and Safety of Farletuzumab in Ovarian Cancer: A Systematic Review and Single-Arm Meta-Analysis - PubMed, accessed October 28, 2025, https://pubmed.ncbi.nlm.nih.gov/39677200/
37. Farletuzumab Ecteribulin Shows Early Activity in Platinum-Resistant Ovarian Cancer, accessed October 28, 2025, https://www.onclive.com/view/farletuzumab-ecteribulin-shows-early-activity-in-platinum-resistant-ovarian-cancer
38. EISAI ANNOUNCES MOVE TO SOLO DEVELOPMENT AND COMMERCIALIZATION OF FARLETUZUMAB ECTERIBULIN (FZEC) ANTIBODY DRUG CONJUGATE (ADC) | News Release：2024, accessed October 28, 2025, https://www.eisai.com/news/2024/news202448.html
39. Eisai and Bristol Myers Squibb Enter Into Global Strategic Collaboration for Eisai's MORAb-202 Antibody Drug Conjugate, accessed October 28, 2025, https://news.bms.com/news/details/2021/Eisai-and-Bristol-Myers-Squibb-Enter-Into-Global-Strategic-Collaboration-for-Eisais-MORAb-202-Antibody-Drug-Conjugate/default.aspx
40. EISAI PRESENTS NEW FINDINGS FOR ANTIBODY DRUG CONJUGATE FARLETUZUMAB ECTERIBULIN AT 2022 ASCO ANNUAL MEETING | News Release, accessed October 28, 2025, https://www.eisai.com/news/2022/news202245.html
41. NCT03386942 | A Study of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin) in Participants With Solid Tumors | ClinicalTrials.gov, accessed October 28, 2025, https://clinicaltrials.gov/study/NCT03386942
42. Safety and efficacy of MORAb-202 in patients (pts) with platinum-resistant ovarian cancer (PROC): Results from the expansion part of a phase 1 trial. - ASCO, accessed October 28, 2025, https://www.asco.org/abstracts-presentations/ABSTRACT364704
43. NCT04300556 | A Study to Evaluate the Safety, Tolerability, and Efficacy of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin), a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Participants With Selected Tumor Types | ClinicalTrials.gov, accessed October 28, 2025, https://clinicaltrials.gov/study/NCT04300556
44. A Study to Evaluate the Safety, Tolerability, and Efficacy of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin), a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Participants With Selected Tumor Types - Clinical Trials | Stanford Medicine, accessed October 28, 2025, https://clinicaltrials.stanford.edu/trials/a/NCT04300556.html
45. NCT05613088 | A Study of MORAb-202 Versus Investigator's Choice Chemotherapy in Female Participants With Platinum-resistant High-grade Serous (HGS) Ovarian, Primary Peritoneal, or Fallopian Tube Cancer | ClinicalTrials.gov, accessed October 28, 2025, https://clinicaltrials.gov/study/NCT05613088
46. Farletuzumab Ecteribulin - Drug Targets, Indications, Patents - Synapse, accessed October 28, 2025, https://synapse-patsnap-com.libproxy1.nus.edu.sg/drug/d0ea44a06a5b406192e7871227104860
47. A phase I study of farletuzumab, a humanized anti-folate receptor α monoclonal antibody, in patients with solid tumors - PMC - NIH, accessed October 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4387250/
48. Eisai Assumes Sole Responsibility for ADC After Collaboration With ..., accessed October 28, 2025, https://www.biospace.com/eisai-assumes-sole-responsibility-for-adc-after-collaboration-with-bms-ends/
49. Eisai Assumes Sole Responsibility for ADC After Collaboration With BMS Ends - BioSpace, accessed October 28, 2025, https://www.biospace.com/eisai-assumes-sole-responsibility-for-adc-after-collaboration-with-bms-ends
50. Search Orphan Drug Designations and Approvals - accessdata.fda ..., accessed October 28, 2025, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=204905
51. European Regulatory Agency Grants Orphan Status to Morphotek ..., accessed October 28, 2025, https://www.eisai.com/news/news200822.html
52. Australian Register of Therapeutic Goods (ARTG), accessed October 28, 2025, https://www.tga.gov.au/products/australian-register-therapeutic-goods-artg
53. Therapeutic Goods Administration (TGA) | Australian Government Department of Health, Disability and Ageing, accessed October 28, 2025, https://www.tga.gov.au/