Briquilimab (JSP191): A Comprehensive Monograph on a Novel Anti-CD117 Monoclonal Antibody

Drug Identification and Physicochemical Properties

Nomenclature and Identifiers

Briquilimab is an investigational biotech therapeutic classified as a protein-based therapy, specifically a monoclonal antibody (mAb).[1] Its development and identification are tracked through a series of standardized nomenclature and registry numbers essential for regulatory, clinical, and research purposes. The generic name assigned to the molecule is Briquilimab.[1] The drug is cataloged in the DrugBank database under the accession number DB18136.[1]

Throughout its development history, Briquilimab has been known by several code designations and synonyms. It was initially developed under the code name AMG 191 (also styled as AMG-191 or AMG191).[1] Following its acquisition and further development by Jasper Therapeutics, it became widely known as JSP191 (also JSP 191 or JSP-191).[1] It is also referred to functionally as an anti-c-Kit monoclonal antibody.[2] These synonyms are critical for tracing the molecule's progression through preclinical and clinical stages across different sponsoring organizations.

For chemical and substance registration, Briquilimab is assigned the Chemical Abstracts Service (CAS) Number 2574591-89-0 and the Unique Ingredient Identifier (UNII) QWX84D0DRC.[1] A summary of these key identifiers is provided in Table 1.

Table 1: Key Identifiers and Properties of Briquilimab

Identifier/Property	Value	Source(s)
Generic Name	Briquilimab	1
DrugBank ID	DB18136	1
CAS Number	2574591-89-0	1
UNII	QWX84D0DRC	1
Code Designations	JSP191, AMG-191	2
Drug Type	Biotech, Monoclonal Antibody	1
Molecular Formula	$C_{6426}H_{9946}N_{1718}O_{2034}S_{46}$	4
Molecular Weight	~145.3 kDa	4

Structural and Molecular Characterization

Briquilimab is a complex biomolecule defined by its specific protein structure, which dictates its function. It is a humanized immunoglobulin G1 (IgG1) kappa monoclonal antibody, produced using recombinant DNA technology in a Chinese hamster ovary (CHO) cell line.[3] The term "humanized" indicates that the constant regions of the antibody are of human origin to minimize immunogenicity, while the complementarity-determining regions (CDRs) responsible for target binding are derived from a murine source and have been grafted onto a human framework.[4]

The complete molecule is a dimer composed of two identical heavy chains and two identical light chains, linked by a series of interchain and intrachain disulfide bridges that maintain its quaternary structure.[4] The heavy chain consists of 447 amino acids, while the light chain comprises 218 amino acids.[4] The total molecular weight of the protein is approximately 145.3 kDa, with a corresponding molecular formula of $C_{6426}H_{9946}N_{1718}O_{2034}S_{46}$.[4]

A defining structural feature of Briquilimab is its engineered aglycosylated state.[6] This modification is not an incidental property but a deliberate and critical design choice central to the drug's safety profile. It is achieved via a specific point mutation in the gene encoding the antibody's heavy chain, at position 297, where the native asparagine (N) residue is substituted with a glutamine (Q) residue (N297Q).[4] This single amino acid change eliminates the consensus sequence for N-linked glycosylation within the CH2 domain of the antibody's Fc (Fragment, crystallizable) region. The functional consequence of this aglycosylation is the mitigation of unwanted mast cell activation.[8] Standard glycosylated IgG1 antibodies can bind to Fc receptors (FcγR) on the surface of mast cells and other immune cells, triggering effector functions such as degranulation. For a therapeutic antibody intended to treat mast cell-driven diseases, such an off-target agonist effect would be a significant liability, potentially inducing the very inflammatory responses the drug is designed to prevent. By removing the glycan structure, the N297Q mutation effectively uncouples the antigen-binding function of the Fab (Fragment, antigen-binding) region from the effector-cell-engaging function of the Fc region. This engineering renders Briquilimab a "pure" antagonist of its target, a crucial feature for its intended therapeutic applications.

Preclinical Pharmacology and Mechanism of Action

Molecular Target: The KIT Receptor (CD117)

The molecular target of Briquilimab is the human CD117 protein, a receptor tyrosine kinase also known as KIT, c-Kit, or the mast/stem cell growth factor receptor (SCFR).[2] CD117 is expressed on the surface of several key cell types, most notably hematopoietic stem cells (HSCs) and mast cells.[2]

The physiological function of CD117 is mediated through its interaction with its endogenous ligand, Stem Cell Factor (SCF).[2] The binding of SCF to CD117 induces receptor dimerization and autophosphorylation, activating a cascade of intracellular signaling pathways. This SCF/CD117 signaling axis is described as essential for the survival, proliferation, differentiation, and maintenance of both the hematopoietic stem cell pool in the bone marrow and the population of tissue-resident mast cells throughout the body.[2] This pathway, therefore, acts as a master regulator for these two distinct cell lineages. The profound dependency of both HSCs and mast cells on this single survival signal provides the biological rationale for Briquilimab's development across seemingly disparate therapeutic areas.

Mechanism of Action (MoA)

Briquilimab exerts its biological effect through a highly specific and direct mechanism of action. Upon administration, the antibody targets and binds with high affinity to the extracellular domain of the CD117 receptor on the cell surface.[2] The affinity constant ($K_D$) for this interaction has been measured at $5.634 \times 10^{-9}$ M.[3]

This binding event physically and competitively blocks the natural ligand, SCF, from accessing its binding site on the receptor.[2] By preventing the SCF/CD117 interaction, Briquilimab effectively shuts down the downstream intracellular signaling cascade that is normally initiated by this binding.[6] In vitro studies have confirmed that this blockade leads to the inhibition of critical survival pathways, including the PI3K/AKT pathway.[8]

The cellular consequence of disrupting this "critical survival signal" is the induction of programmed cell death, or apoptosis, in cells that are dependent upon it.[6] For both HSCs and mast cells, continuous signaling through CD117 is required for their maintenance; its withdrawal triggers an intrinsic apoptotic program. The Bim-mediated pathway has been specifically implicated in the induction of mast cell apoptosis following CD117 blockade.[6]

This single mechanism of action is leveraged to achieve two distinct therapeutic outcomes:

1. HSC Depletion for Transplant Conditioning: In the context of hematopoietic cell transplantation (HCT), the induction of apoptosis in host HSCs depletes them from their protective niches within the bone marrow. This "emptying of the niche" creates the necessary space for incoming donor stem cells to engraft and reconstitute a new blood and immune system.[2]
2. Mast Cell Depletion for Inflammatory Diseases: In mast cell-mediated diseases, the induction of apoptosis in tissue-resident mast cells removes the primary cellular source of the inflammatory mediators (e.g., histamine, tryptase, cytokines) that drive the symptoms of conditions like chronic urticaria and asthma.[6]

Preclinical Evidence

The proposed mechanism of action and therapeutic potential of Briquilimab are supported by a body of preclinical evidence from both in vitro and in vivo models.

In Vitro Studies:

Experiments using KIT-expressing cell lines and primary human mast cells have demonstrated that Briquilimab potently blocks SCF binding to its receptor. This blockade translates to a functional inhibition of SCF/KIT signaling, which in turn prevents mast cell degranulation and compromises mast cell survival, ultimately leading to apoptosis.8 The half-maximal effective concentration ($EC_{50}$) for Briquilimab binding to immobilized human c-Kit protein was determined to be 1.72 ng/mL.3

In Vivo Animal Models:

Studies in animal models have been crucial for establishing proof-of-concept for safety and efficacy.

• Non-Human Primates (NHPs): Given the high homology between human and NHP CD117, these models are particularly relevant. In cynomolgus macaques, administration of Briquilimab was found to be well-tolerated. Single and multiple doses led to profound, durable, and dose-dependent depletion of tissue-resident mast cells in key organs, including the lung, skin, and colon.[8] This broad systemic activity is desirable for treating systemic mast cell diseases, but it also provides an early indication of potential on-target effects that would require monitoring in human trials, such as effects on mast cells in the gastrointestinal tract.
• Mouse Models: Standard mice are not suitable for testing a human-specific antibody. To overcome this, a novel mouse model was generated expressing a chimeric CD117 receptor, which contains the human extracellular domain (the target of Briquilimab) and the murine intracellular domain.[10] In these specialized mice, Briquilimab effectively depleted mast cells and, importantly, prevented a systemic anaphylactic reaction induced by IgE, providing direct evidence of its potential to treat severe allergic conditions.[10] In separate studies using immunodeficient mice engrafted with human cells (xenograft models), Briquilimab demonstrated its ability to deplete human HSCs, supporting its application as an HCT conditioning agent.[3]

Clinical Pharmacology: Pharmacokinetics and Pharmacodynamics

The clinical pharmacology of Briquilimab describes its absorption, distribution, metabolism, and excretion (pharmacokinetics, PK) and its biochemical and physiological effects on the body (pharmacodynamics, PD). The relationship between these two domains is fundamental to designing safe and effective dosing regimens.

Pharmacokinetics (PK)

The pharmacokinetic profile of Briquilimab has been characterized in healthy volunteers and in patient populations with severe combined immunodeficiency (SCID), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML).[15]

A population PK analysis, conducted on data from 49 patients receiving single intravenous infusions, determined that the disposition of Briquilimab is best described by a two-compartment model.[15] This model incorporates both linear and non-linear (Michaelis-Menten) elimination pathways. The presence of non-linear, saturable elimination means that as the drug concentration increases, the clearance mechanisms can become saturated. This leads to a slower rate of elimination at higher doses and results in a greater-than-proportional increase in drug exposure (AUC) with increasing doses, a phenomenon that was also observed in a study of healthy volunteers receiving subcutaneous doses.[15]

The only patient characteristic identified as a significant covariate influencing Briquilimab's PK was body weight, which affected both the volume of distribution and the elimination rate.[15] This finding supports the use of weight-based dosing (mg/kg) in the HCT setting to achieve more predictable and consistent drug exposure across patients of different sizes.

A key pharmacokinetic parameter is the drug's half-life. Following subcutaneous administration, Briquilimab exhibits a half-life of approximately 9 days.[17] This relatively long half-life is a critical feature, as it allows for intermittent dosing schedules, such as every 8 or 12 weeks, which are being explored in clinical trials for chronic conditions.[17]

In the specialized context of HCT conditioning, understanding the drug's clearance is paramount to patient safety. The PK model is used as a clinical tool to guide the timing of subsequent steps in the transplant protocol. Real-time PK measurements are taken after Briquilimab administration to predict when the serum concentration will fall below a predefined threshold (e.g., 500 ng/mL, 1000 ng/mL) that is considered safe for the infusion of the donor hematopoietic cell graft.[15] This personalized approach, based on individual patient PK, ensures that residual Briquilimab does not impair the engraftment of the new donor cells. For a typical patient receiving a 0.6 mg/kg intravenous dose, the model predicted a median time of 12.3 days to reach a target concentration of 500 ng/mL.[15]

Pharmacodynamics (PD)

The pharmacodynamic effects of Briquilimab are the direct, measurable consequences of its mechanism of action: the depletion of CD117-expressing cells. These effects are monitored using both direct cell counts and validated surrogate biomarkers.

In the HCT setting, the primary PD effect is the depletion of hematopoietic stem and progenitor cells (HSPCs). This was measured directly in the Phase 1 AML/MDS trial via bone marrow biopsies. The results showed that a single dose of Briquilimab, administered before any other conditioning agents, resulted in a mean decrease of 62.4% in bone marrow HSPCs compared to baseline.[13]

In the context of mast cell diseases, the PD effect is the depletion of mast cells in affected tissues. This has been assessed directly in healthy volunteers through skin punch biopsies. Following single subcutaneous doses of 84 mg or higher, a consistent decrease in skin mast cell counts was observed by day 7, with a more pronounced reduction seen by day 29 at higher dose levels.[16] This finding confirms that a single dose can produce a durable biological effect lasting for at least a month.

Because obtaining tissue biopsies is invasive, a less invasive surrogate biomarker is used to monitor mast cell depletion in the urticaria clinical trials: serum tryptase. Tryptase is an enzyme stored in mast cell granules and released upon activation or cell turnover. Its level in the blood is proportional to the total body mast cell load. Clinical trials in both chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) have consistently shown that Briquilimab administration leads to rapid, deep, and prolonged reductions in serum tryptase levels.[9] In some cohorts receiving higher doses, tryptase levels fell below the lower limit of quantification, indicating a profound degree of systemic mast cell depletion.[9]

The correlation between drug exposure (PK) and biological effect (PD) is evident. The degree of mast cell depletion in healthy volunteers appeared to correlate with Briquilimab exposure.[16] Similarly, the clinical response in urticaria trials is dose-dependent, with higher doses leading to more durable symptomatic improvement.[19] This strong PK/PD relationship, combined with the long half-life, provides the scientific foundation for the intermittent dosing strategy pursued by the developer. This strategy aims to achieve initial mast cell depletion followed by a prolonged drug-free interval, which may minimize the potential for long-term on-target side effects by allowing CD117 signaling to return on other cell types between doses.[6]

Clinical Development and Efficacy

The clinical development of Briquilimab has advanced along two parallel tracks, leveraging its unified mechanism of action to address two distinct sets of medical needs: as a conditioning agent for hematopoietic cell transplantation and as a primary therapy for mast cell-mediated diseases.

Application as a Hematopoietic Cell Transplant (HCT) Conditioning Agent

The primary rationale for using Briquilimab in the HCT setting is to provide a targeted, non-genotoxic conditioning regimen. Traditional conditioning relies on high-dose chemotherapy and/or total body irradiation to ablate the patient's hematopoietic system. While effective, these methods are associated with severe, often life-threatening, toxicities that limit their use, particularly in older, frail, or heavily pre-treated patients.[13] Briquilimab offers a potential alternative that specifically depletes host HSCs to create niche space for donor cells, with the goal of minimizing the collateral damage associated with conventional myeloablative approaches.[2]

Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS)

A key study in this program was a Phase 1 trial (NCT04429191) evaluating Briquilimab in older or frail adults with AML in complete remission (CR) or with MDS who were candidates for allogeneic HCT.[13] The regimen consisted of a single intravenous dose of Briquilimab (0.6 mg/kg) followed by a standard non-myeloablative conditioning backbone of low-dose total body irradiation (TBI) and fludarabine.[13]

The final one-year results from this study, which enrolled 32 patients, demonstrated the regimen's feasibility and efficacy. Key outcomes are summarized in Table 2. All subjects successfully engrafted, with neutrophil recovery occurring between 19 and 26 days post-transplant.[13] Critically, the regimen achieved high levels of donor chimerism, with a median donor myeloid chimerism of 99% at day +90, indicating near-complete replacement of the host's myeloid system with donor-derived cells.[13] The regimen also proved effective at clearing measurable residual disease (MRD), a key predictor of relapse. Among patients who were MRD-positive at baseline, 70% of those with AML and 43% of those with MDS converted to MRD-negative status by one year post-transplant.[18]

However, the study also identified a significant limitation. The regimen was not effective for the five MDS subjects whose disease was characterized by a TP53 mutation. All of these high-risk patients experienced disease progression or relapse.[13] This important finding suggests that while Briquilimab-based conditioning is effective at clearing marrow niches and facilitating donor engraftment, it may not be sufficient to overcome the aggressive biology of certain high-risk genetic subtypes. This underscores the need for biomarker-based patient selection in future trials, distinguishing Briquilimab's role as a potent niche-clearing agent from that of a direct anti-leukemic therapy for high-risk disease.

Table 2: Summary of Efficacy and Safety Outcomes from the Phase 1 HCT Study in AML/MDS (NCT04429191)

Outcome (at 1-Year Post-HCT)	AML in CR (n=13)	MDS (n=16)	Source(s)
Engraftment	100%	100%	13
Relapse/Progression	3 (23.1%)	5 (31.3%)	13
Non-Relapse Mortality (NRM)	1 (7.7%)	1 (6.3%)	13
Relapse-Free Survival (RFS)	9 (69.2%)	8 (50.0%)	18
Overall Survival (OS)	9 (69.2%)	8 (50.0%)	18
MRD Negative	8 (61.5%)	6 (37.5%)	13
Grade 3-4 Acute GVHD	\multicolumn{2}{c	}{1 of 32 total subjects (3.1%)}	13
Severe Chronic GVHD	\multicolumn{2}{c	}{0 of 32 total subjects (0%)}	13

Other Hematological and Genetic Diseases

The potential of Briquilimab as a platform conditioning agent has been explored in several other rare and severe diseases, including Severe Combined Immunodeficiency (SCID), Fanconi Anemia (FA), Sickle Cell Disease (SCD), and GATA2 Deficiency.[12] While these programs demonstrated the broad applicability of the therapeutic concept, a subsequent corporate reorganization led to the halting of the SCID study to focus resources on other indications.[27]

Application in Mast Cell-Mediated Diseases

The second major development arm for Briquilimab focuses on its ability to deplete tissue mast cells, which are the central drivers of pathology in a range of allergic and inflammatory disorders. By eliminating these cells, Briquilimab aims to remove the underlying source of the disease rather than merely blocking the effects of the mediators they release.[6]

Chronic Spontaneous Urticaria (CSU)

The lead indication in this program is Chronic Spontaneous Urticaria (CSU), a debilitating skin condition characterized by recurrent hives and itching. The BEACON study (NCT06162728) is a Phase 1b/2a randomized, placebo-controlled, dose-escalation trial in adult patients with moderate-to-severe CSU who have an inadequate response to standard therapies, including high-dose antihistamines and/or the approved biologic omalizumab.[21] The primary efficacy endpoint is the Urticaria Activity Score over 7 days (UAS7), a patient-reported outcome on a 42-point scale where a score of 0 indicates a complete response (no hives or itch).[21]

The results from this study have been exceptionally strong, demonstrating rapid, profound, and durable clinical responses that are dose-dependent.[9] As shown in Table 3, higher doses of Briquilimab led to dramatic improvements in UAS7 scores compared to placebo. The 240 mg single-dose cohort was particularly noteworthy, with 100% of participants (N=3 in the initial report, later updated to N=5) achieving a complete response (UAS7=0).[9] The 180 mg every-8-weeks (Q8W) regimen in an open-label extension study also showed robust efficacy, with 73% of patients achieving a complete response at 12 weeks.[20] Such high rates of complete response in a refractory patient population suggest a highly potent therapeutic effect.

Table 3: Efficacy Results from the BEACON Study in Chronic Spontaneous Urticaria Across Dosing Cohorts

Dosing Regimen	Baseline UAS7 (Mean)	Mean Change from Baseline	% Achieving Well-Controlled (UAS7≤6)	% Achieving Complete Response (UAS7=0)	Timepoint	Source(s)
120 mg Q12W (N=4)	28.8	-29.8	75%	50%	Week 16	21
180 mg Q12W (N=7)	27.8	-21.7	57%	57%	Week 16	21
240 mg Single Dose (N=3)	26.6	-26.6	100%	100%	Week 8	19
Placebo (N=12)	28.6	-10.1 to -12.4	25%	17%	Week 8/16	19

Chronic Inducible Urticaria (CIndU)

Briquilimab is also being evaluated in Chronic Inducible Urticaria (CIndU), where hives are triggered by specific physical stimuli. The SPOTLIGHT study (NCT06353971) is a Phase 1b/2a open-label trial in patients with Cold Urticaria (ColdU) or Symptomatic Dermographism (SD).[30] Efficacy is measured by response to standardized provocation tests. The results have mirrored the high efficacy seen in CSU. In the 180 mg single-dose cohort, 92% of participants (11 of 12) achieved a complete response, and 100% achieved a clinical response.[31] The responses were rapid, with two-thirds of patients responding by the second week after dosing.[31]

Major Development Setback: Drug Product Lot Issue

Despite the outstanding efficacy data, the Briquilimab program suffered a major setback due to a manufacturing issue. In July 2025, Jasper Therapeutics reported that results from two cohorts in the BEACON trial (240 mg Q8W and a 240 mg loading dose followed by 180 mg Q8W) were confounded by a problem with a single drug product lot.[20] Patients who received the drug from the affected lot showed lower-than-expected reductions in serum tryptase and no discernible clinical benefit, in stark contrast to the profound effects seen with other lots.[20] This critical Chemistry, Manufacturing, and Controls (CMC) failure forced the company to halt the ETESIAN trial in asthma (which had used the same lot) and to delay the planned pivotal Phase 2b study in CSU until mid-2026 to allow time to investigate the issue and re-run the affected cohorts with a reliable product.[20] This incident has shifted the primary risk of the program from biological uncertainty to operational and manufacturing reliability.

Comprehensive Safety and Tolerability Profile

The safety and tolerability profile of Briquilimab is a critical component of its overall risk-benefit assessment. The profile must be interpreted within the specific clinical context of its use, as the acceptable level of risk differs dramatically between a life-threatening malignancy requiring HCT and a chronic but non-fatal dermatologic condition.

Safety Profile in HCT Conditioning

In the high-risk setting of allogeneic HCT for older and frail patients with AML or MDS, the Briquilimab-based conditioning regimen was described as safe and well-tolerated.[13] A key finding from the Phase 1 study was the absence of acute toxicity directly attributable to the drug itself; there were no reported infusion toxicities and, more importantly, no briquilimab-related Serious Adverse Events (SAEs).[13]

The severe adverse events and mortalities observed in the trial were consistent with the known, high-risk nature of the allogeneic transplant procedure in this vulnerable population. Of the 32 enrolled subjects, there was one case of Grade 3-4 acute Graft-versus-Host Disease (GVHD), a severe immune reaction of donor cells against the recipient's body.[13] There were no cases of severe chronic GVHD. By one year, there were two cases of non-relapse mortality (NRM): one death from complications of GVHD and one from sepsis.[13] These events, while tragic, are recognized complications of the HCT procedure and were not attributed to Briquilimab. The data, therefore, suggests that adding Briquilimab to a non-myeloablative backbone does not introduce significant additional toxicity, supporting its rationale as a safer conditioning agent.

Safety Profile in Urticaria and Healthy Volunteers

In stark contrast to the HCT setting, the safety profile in studies for chronic urticaria and in healthy volunteers is characterized by a much lower overall event rate, with no dose-limiting toxicities observed.[19] The adverse events reported are generally low-grade and consistent with the drug's on-target mechanism of action.

The most common on-target adverse event is a predictable, mild-to-moderate, and transient decrease in neutrophil counts.[19] This is an expected consequence of Briquilimab's effect on hematopoietic progenitor cells. Crucially, these decreases have generally been self-resolving, with counts recovering before the next scheduled dose, and have not been associated with an increased risk of fever or infection.[19] A single Grade 3 neutropenia event was reported, but this occurred in a participant with a pre-existing history of idiopathic neutropenia.[19] The predictable and manageable nature of this on-target effect suggests it may not be a barrier to approval for chronic use, provided it is properly monitored.

Another on-target effect, dysgeusia (a distortion of the sense of taste), was reported and led to the decision to halt dose escalation at 420 mg in a healthy volunteer study, suggesting a potential ceiling for the tolerated dose.[16] Other adverse events reported in more than 10% of healthy volunteers included nausea, upper respiratory tract infection, dizziness, back pain, and lethargy, though these did not show a clear relationship with the dose.[16]

Importantly, several potential side effects associated with other KIT inhibitors have not been observed in the urticaria trials. Specifically, there have been no reported adverse events related to changes in hair or skin color, hypersensitivity reactions, or anemia.[32] This favorable profile, summarized in Table 4, supports the potential for Briquilimab to be a well-tolerated long-term therapy for chronic mast cell diseases.

Table 4: Consolidated Summary of Reported Adverse Events Across Major Clinical Programs

Adverse Event	Program	Frequency / Severity	Notes	Source(s)
Neutropenia	Urticaria	Mild-to-moderate, transient. Single Grade 3 event in a patient with prior history.	Predictable on-target effect. Resolves between doses. Not associated with infection.	19
Dysgeusia (Taste Change)	Healthy Volunteers, Urticaria	Low frequency, low grade. Halted dose escalation at 420 mg in HV study.	On-target effect.	16
Grade 3-4 Acute GVHD	HCT (AML/MDS)	1 of 32 subjects (3.1%)	Procedure-related complication, not attributed to Briquilimab.	13
Non-Relapse Mortality	HCT (AML/MDS)	2 of 32 subjects (6.3%) by 1 year	Deaths due to GVHD and sepsis; known risks of HCT procedure.	13
Drug-Related SAEs	All Programs	None reported	Briquilimab has not been associated with any Serious Adverse Events.	13
Infusion Toxicities	HCT (AML/MDS)	None reported	Well-tolerated upon intravenous administration.	13

Regulatory Status and Corporate Strategy

The development path of Briquilimab is shaped by interactions with global regulatory agencies and the strategic decisions of its developer, Jasper Therapeutics, Inc.

Regulatory Designations

Briquilimab has received several special designations from major regulatory bodies that are intended to facilitate the development of drugs for rare or serious conditions.

• European Medicines Agency (EMA): The EMA has granted Orphan Drug Designation to Briquilimab for its use as a conditioning treatment prior to hematopoietic stem cell transplant.[22] This designation provides incentives, such as market exclusivity, to encourage the development of therapies for rare diseases.
• U.S. Food and Drug Administration (FDA): The FDA has also granted Briquilimab Orphan Drug Designation for its use in HCT.[22] In addition, it received a Rare Pediatric Disease Designation for the conditioning treatment of patients with SCID, highlighting its potential to address a critical unmet need in a vulnerable pediatric population.[22] Furthermore, the FDA cleared the Investigational New Drug (IND) application for the BEACON study, which allowed the clinical program in chronic spontaneous urticaria to proceed in the United States.[23]
• Therapeutic Goods Administration (TGA), Australia: The provided documentation contains no specific information regarding the regulatory status of Briquilimab with the TGA in Australia.[6]

Corporate and Development Strategy

Briquilimab is being developed by Jasper Therapeutics, Inc., a clinical-stage biotechnology company publicly traded on the Nasdaq stock exchange (JSPR).[23] The company's strategy has undergone a significant evolution, driven by both clinical success and operational challenges.

In July 2025, in response to the confluence of exceptionally promising efficacy data in urticaria and the critical manufacturing failure, Jasper Therapeutics announced a major corporate reorganization.[27] This strategic pivot was designed to conserve capital and focus all available resources on its most promising asset. The company made the decision to bet its future on the chronic urticaria program, which represents a large commercial market and where the drug has shown potentially best-in-class efficacy.

The consequences of this reorganization were significant. The company's clinical focus was narrowed exclusively to the ongoing trials in chronic urticaria: the BEACON study in CSU, the SPOTLIGHT study in CIndU, and their associated open-label extension study.[27] All other clinical and preclinical programs were halted, including the ETESIAN study in asthma, the study in SCID, and various investigator-sponsored trials.[27] This strategic retreat was not necessarily a reflection of a lack of scientific merit in the halted programs but an economic necessity to weather the delay and additional expense caused by the manufacturing setback. The reorganization also involved a workforce reduction of approximately 50% and a transition in the role of Chief Medical Officer, signaling a company-wide effort to streamline operations and extend its cash runway.[27]

Synthesis and Future Outlook

Summary of Briquilimab's Profile

Briquilimab has emerged as a highly promising, precisely engineered therapeutic agent. It is a humanized, aglycosylated anti-CD117 monoclonal antibody with a well-defined mechanism of action: the targeted depletion of hematopoietic stem cells and mast cells via blockade of the essential SCF/CD117 survival pathway. This singular mechanism has been effectively leveraged to establish compelling clinical proof-of-concept in two fundamentally different therapeutic areas. As a conditioning agent for HCT, it offers the potential for a safer, less toxic path to curative transplantation. As a primary therapy for chronic urticaria, it has demonstrated an unprecedented level of efficacy, with a speed and depth of response that could position it as a transformative treatment for patients with refractory disease. Its safety profile appears manageable and is highly dependent on the clinical context, characterized by low-grade, predictable on-target effects in ambulatory settings and minimal added toxicity in the high-risk HCT environment.

Key Challenges and Unanswered Questions

Despite its immense promise, the Briquilimab program faces critical challenges that must be overcome to realize its potential.

1. Manufacturing and CMC: The single greatest hurdle is the resolution of the drug product lot issue that confounded the BEACON trial. This incident has elevated manufacturing and quality control from a routine operational task to the primary gating factor for the entire program. Jasper Therapeutics must demonstrate to regulators and potential partners that it has identified the root cause of the product inconsistency and has implemented robust, validated processes to ensure the reliable production of a consistent, active drug product.
2. Long-Term Safety: While the short- and medium-term safety data are encouraging, the long-term consequences of profound and chronic mast cell depletion in humans are not yet fully understood. Mast cells play roles in host defense and tissue homeostasis, and their long-term absence could have unforeseen effects. Continued data collection from the open-label extension studies will be critical to building confidence in the long-term safety profile.
3. Competitive Landscape: Briquilimab does not exist in a vacuum. In the large and lucrative chronic urticaria market, it will need to compete with established biologics like omalizumab and a pipeline of other novel agents targeting different pathways. Its ultimate commercial success will depend on its ability to demonstrate a clearly differentiated and superior profile based on its speed of onset, the high rate of complete responses, the durability of its effect, and the convenience of its intermittent dosing schedule.

Future Outlook

The immediate trajectory of Briquilimab is contingent on the successful resolution of its manufacturing challenges. The company's ability to replicate the impressive efficacy data in the newly enrolled BEACON cohorts with a consistent drug product will be the definitive test.

If this hurdle is cleared, Briquilimab has the potential to become a best-in-class therapy for chronic spontaneous and inducible urticaria. Its novel mechanism of action, targeting the root cellular cause of the disease, could offer a powerful new option for the significant number of patients who are refractory to or have an inadequate response to existing treatments.

The hematopoietic cell transplantation programs, though currently de-prioritized due to corporate strategy, hold significant long-term value. They represent a potential paradigm shift in conditioning, promising to make curative cell and gene therapies accessible to a wider range of patients with devastating hematologic and genetic diseases. These programs could be revived internally or out-licensed to a partner in the future.

Ultimately, the story of Briquilimab will serve as a compelling case study in drug development, testing whether extraordinary clinical efficacy and a strong scientific rationale can overcome significant operational and manufacturing setbacks on the arduous path to regulatory approval and patient access.

Works cited

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