Comprehensive Report on BMS-986322 (Lomedeucitinib)

1. Introduction

Overview of BMS-986322 (Lomedeucitinib)

BMS-986322, also known by its United States Adopted Name (USAN) Lomedeucitinib, is an investigational small molecule drug developed by Bristol-Myers Squibb (BMS).[1] It was classified as a New Molecular Entity and primarily investigated for its potential in treating immune-mediated conditions, with a significant focus on moderate-to-severe psoriasis.[1] The compound progressed to Phase II clinical trials. However, despite being characterized as a "second-generation" Tyrosine Kinase 2 (TYK2) inhibitor, its development was subsequently deprioritized by BMS.[1]

The journey of BMS-986322 from a promising next-iteration therapeutic candidate to a shelved asset provides a pertinent example of the complex decision-making processes within pharmaceutical research and development (R&D). As a "second-generation" TYK2 inhibitor [5], BMS-986322 was presumably designed to offer improvements over existing or preceding TYK2 inhibitors, potentially including BMS's own successful drug, deucravacitinib (Sotyktu). The fact that its development was halted after Phase II trials, with the company citing a strategic imperative to maximize the potential of Sotyktu [5], indicates the exceptionally high threshold that new drug candidates must meet. To justify displacing or significantly augmenting an already successful first-in-class or best-in-class therapy from the same developer, a follow-on compound must demonstrate substantial incremental benefits that clearly outweigh the considerable development costs, regulatory navigation, and potential market complexities. The deprioritization of BMS-986322 suggests that it either did not meet this demanding criterion or that the commercial and developmental prospects of Sotyktu were deemed sufficiently robust to not necessitate a direct successor at that time. This situation underscores the rigorous internal and external competitive pressures in drug development, where even scientifically sound candidates can be discontinued due to strategic business decisions, resource allocation priorities, and the formidable benchmarks set by existing treatments.

Purpose and Scope of the Report

This report aims to provide a comprehensive overview of BMS-986322 (Lomedeucitinib), consolidating available public information regarding its chemical characteristics, pharmacological profile, mechanism of action, clinical development program, and ultimate development status. The information presented is drawn from drug information databases, clinical trial registries, company communications, and relevant scientific literature.

2. Chemical and Pharmacological Profile

2.1. Nomenclature and Identifiers

Consistent nomenclature and unique identifiers are crucial for accurately tracking information on investigational compounds across various research and regulatory databases.

• Drug Names: BMS-986322; Lomedeucitinib (USAN, INN).[1]
• Synonyms: BMS 986322, bms986322, BMS-986322-01.[2]
• CAS Number: 2328068-29-5.[6]
• Other Identifiers:
• UNII: EYQ7KA55XA.[6]
• ChEMBL ID: CHEMBL5314608.[6]
• KEGG ID: D12725.[6]
• NCI Thesaurus Code: C203082.[6]

2.2. Chemical Structure and Properties

The physicochemical properties of BMS-986322 are fundamental to its formulation, delivery, and biological activity.

• Molecular Formula: C18​H20​N6​O4​S.[6] Several sources indicate the presence of deuterium, specifically as C18​H17​D3​N6​O4​S.[7] The PubChem entry for Lomedeucitinib includes the synonym "N-(methyl-d3)-4-[[3-(methylsulfonyl)-2-pyridinyl]amino]-6-pent-1-ylcarbonyl]amino]-pyridazine-3-carboxamide" and a SMILES string incorporating deuterium: [2H]C([2H])([2H])NC(=O)C1=NN=C(C=C1NC2=C(C=CC=N2)S(=O)(=O)C)NC(=O)[C@@H]3CC34CC4.[6]
• Molecular Weight: Approximately 419.5 g/mol (exact value varies slightly based on deuteration, e.g., 419.47 g/mol for the deuterated form).[6]
• Drug Type/Modality: Small molecule drug.[2]
• Physical Appearance: Described as a solid; white to off-white in color.[7]
• Solubility: Reported solubility in DMSO is 100 mg/mL (238.40 mM), requiring ultrasonic assistance. It is noted that hygroscopic DMSO can significantly impact product solubility.[9]
• Storage: Recommended storage for the powder form is -20°C for up to 3 years. When in solvent, storage at -80°C for 6 months is advised.[8]

The consistent notation of deuterium, particularly as an N-(methyl-d3) moiety, across multiple independent sources (including chemical databases like PubChem and commercial supplier information) strongly suggests that deuteration was an intentional medicinal chemistry strategy employed in the design of BMS-986322.[6] Deuteration involves replacing one or more hydrogen atoms with deuterium atoms. This substitution can significantly alter a drug's metabolic profile because the carbon-deuterium (C-D) bond is stronger than the carbon-hydrogen (C-H) bond. Consequently, metabolic enzymes may break C-D bonds at a slower rate, a phenomenon known as the kinetic isotope effect. This can lead to several potential pharmacokinetic advantages, such as increased metabolic stability, reduced rate of formation of certain metabolites (which could be inactive or toxic), prolonged plasma half-life, and increased overall drug exposure. For a compound like BMS-986322, positioned as a "second-generation" TYK2 inhibitor [5], deuteration might have been explored as a means to optimize its properties relative to a non-deuterated precursor or to differentiate it from other TYK2 inhibitors, including BMS's own deucravacitinib (which is also deuterated, albeit at a different position on a triazole-methyl group). The fact that the drug was deprioritized despite this potential optimization strategy raises questions about whether the benefits of deuteration translated into sufficiently meaningful clinical advantages in efficacy or safety, or if other factors ultimately determined its fate.

2.3. Pharmacological Class

• Class: Antipsoriatics; TYK2 kinase inhibitors.[1] This classification places BMS-986322 within a group of therapeutic agents aimed at treating psoriasis and, more specifically, within a mechanistic class focused on the inhibition of Tyrosine Kinase 2.

2.4. Mechanism of Action (MOA)

• Target: Tyrosine Kinase 2 (TYK2).[1]
• Action: Inhibitor.[1]
• Detailed MOA: TYK2 is an intracellular, non-receptor tyrosine kinase belonging to the Janus kinase (JAK) family. JAKs are essential mediators in the signaling pathways of numerous cytokines and growth factors. Upon cytokine binding to its receptor, JAKs, including TYK2, become activated and phosphorylate tyrosine residues on the receptor and on themselves. These phosphorylated sites then serve as docking stations for STAT (Signal Transducer and Activator of Transcription) proteins, which are subsequently phosphorylated by JAKs, dimerize, and translocate to the nucleus to regulate gene expression.[5] TYK2 is particularly involved in the signaling pathways for cytokines such as interleukin-12 (IL-12), interleukin-23 (IL-23), and Type I interferons (IFNs), all ofwhich are implicated in the pathogenesis of various autoimmune and inflammatory diseases, including psoriasis.[5] By inhibiting TYK2, BMS-986322 is designed to disrupt these pro-inflammatory signaling cascades, thereby reducing inflammation. Specifically, Lomedeucitinib has been reported to exhibit a significant inhibitory effect on IFNα production downstream of IL-12/TYK2 signaling, with an IC50​ value of 0.047 μM.[8]

There is some ambiguity in the available information regarding the precise binding mode of BMS-986322 to TYK2. One source, referencing an SEC filing, describes BMS-986322 as a "Phase 1 clinical stage allosteric TYK2 inhibitor".[2] Allosteric inhibitors bind to a site distinct from the enzyme's active (ATP-binding) site, inducing a conformational change that modulates enzyme activity. BMS's approved TYK2 inhibitor, deucravacitinib (BMS-986165, Sotyktu), is a well-characterized allosteric inhibitor that binds to the regulatory pseudokinase (JH2) domain of TYK2, conferring high selectivity for TYK2 over other JAK family members.[5] However, another source discussing TYK2 inhibitors more broadly highlights deucravacitinib as "a representative allosteric inhibitor" and ropsacitinib (PF-06826647) as an "active site-directed inhibitor" (i.e., ATP-competitive, binding to the kinase (JH1) domain), without explicitly categorizing BMS-986322.[5] If BMS-986322 were also an allosteric inhibitor and intended as a "second-generation" compound, it would suggest an attempt to refine or improve upon deucravacitinib's allosteric mechanism or properties. Conversely, if it were an ATP-competitive inhibitor, it would represent a different therapeutic approach within BMS's TYK2 portfolio. The specific binding site (JH1 versus JH2 domain) is a critical detail, as it significantly influences an inhibitor's selectivity profile, potential for off-target effects, and overall pharmacological characteristics. The lack of definitive and consistent information on this aspect for BMS-986322 represents a gap in its publicly available profile.

The pursuit of TYK2-selective inhibition aims to improve the safety profile compared to pan-JAK inhibitors, which block multiple JAK isoforms and are associated with broader immunosuppression and a range of adverse effects.[5]

Table 1: BMS-986322 (Lomedeucitinib) - Key Identifiers and Properties

Property	Value	Source(s)
Generic Name (USAN/INN)	Lomedeucitinib	2
Development Code	BMS-986322	1
CAS Number	2328068-29-5	6
Molecular Formula	C18​H20​N6​O4​S; or C18​H17​D3​N6​O4​S (deuterated)	6
Molecular Weight	Approx. 419.5 g/mol	6
Drug Type	Small molecule	2
Pharmacological Class	Antipsoriatics, TYK2 kinase inhibitors	1
Primary Target	Tyrosine Kinase 2 (TYK2)	1
Mechanism of Action (briefly)	Inhibits TYK2, involved in IL-12, IL-23, Type I IFN signaling. Inhibits IFNα production (IC50​=0.047μM) downstream of IL-12/TYK2.	5

3. Non-Clinical Development

Detailed results from specific non-clinical studies for BMS-986322, such as comprehensive toxicology assessments or efficacy in animal models of psoriasis, are not extensively available in the provided public domain information. However, the progression of BMS-986322 into Phase I and subsequently Phase II clinical trials inherently signifies that the compound successfully completed a standard battery of non-clinical evaluations.[1] Before any investigational drug can be administered to humans, regulatory authorities worldwide, including the U.S. Food and Drug Administration (FDA), mandate the submission of extensive preclinical data as part of an Investigational New Drug (IND) application or its equivalent. This data package must demonstrate not only a plausible mechanism of action and potential efficacy in relevant in vitro and in vivo models but also an acceptable safety profile derived from animal pharmacology and toxicology studies.

Therefore, it can be inferred that BMS-986322 showed promising activity in non-clinical models relevant to inflammation and/or psoriasis and passed requisite safety pharmacology and toxicology assessments to support human testing. The reported in vitro data indicating potent inhibition of IFNα production (IC50​=0.047μM) serves as a specific example of its non-clinical activity.[8] The general lack of detailed published preclinical data is not uncommon for drug candidates whose development is discontinued, as the focus of dissemination often shifts away from early-stage research once a decision is made not to proceed to market.

4. Clinical Development Program

4.1. Overview of Clinical Trials

BMS-986322 (Lomedeucitinib) was evaluated in several clinical trials, primarily focusing on establishing its safety, tolerability, and pharmacokinetic (PK) profile in healthy volunteers, and subsequently assessing its efficacy and safety in patients with psoriasis.[1] The highest phase of development achieved for BMS-986322 was Phase II for the treatment of psoriasis.[1]

4.2. Phase I Studies

A comprehensive Phase I program was conducted to characterize the initial clinical profile of BMS-986322.

• NCT06088264: This was a Phase 1, single-center, open-label study designed to evaluate the pharmacokinetics, metabolism, and excretion (ADME) of a single oral dose of [14C]-labeled BMS-986322 in healthy adult male participants.[5] The study was sponsored by Bristol Myers Squibb Co. and conducted in the USA.[1] It commenced on October 31, 2023, and was completed on December 22, 2023.[1] Such studies are crucial for understanding how a drug is absorbed, distributed, metabolized, and eliminated by the human body.
• NCT05615012: This Phase 1, open-label, single-sequence crossover study investigated potential drug-drug interactions (DDIs). It assessed the effect of multiple oral doses of BMS-986322 at steady-state on the pharmacokinetics of rosuvastatin (a commonly prescribed statin), metformin (an antidiabetic drug), and methotrexate (an immunosuppressant often used in autoimmune diseases) in healthy volunteers.[1] Sponsored by Bristol Myers Squibb Co., this trial was conducted in the USA, initiated on November 11, 2022, and completed on December 13, 2023.[1] Understanding DDI potential is vital for ensuring the safe co-administration of a new drug with other medications.
• NCT04175925 (Trial ID IM032-007): This study aimed to assess the drug levels (pharmacokinetics), drug effects (pharmacodynamics), and safety of variable doses of BMS-986322 compared to placebo in healthy participants. It also evaluated the effects of food on the drug's absorption and how bodily acidity levels might influence it.[10] The trial has been completed, and results are anticipated to be posted on ClinicalTrials.gov when available.[10] This type of study typically involves single ascending dose (SAD) and multiple ascending dose (MAD) cohorts to establish initial safety, tolerability, and PK/PD characteristics.

The execution of these dedicated ADME and DDI studies, in addition to standard SAD/MAD and food effect assessments, indicates a systematic and thorough approach by BMS to characterize the fundamental clinical pharmacology of BMS-986322. Such a comprehensive early-phase program often reflects a significant initial commitment to a drug candidate's development, making its subsequent deprioritization after Phase II particularly noteworthy.

4.3. Phase II Studies

The primary efficacy-seeking trial for BMS-986322 was conducted in patients with psoriasis.

• NCT05730725 (Trial ID IM032-041): This was a multi-center, randomized, double-blind, placebo-controlled, parallel-group Phase 2 study designed to evaluate the clinical efficacy and safety of BMS-986322 in adult participants with moderate-to-severe plaque psoriasis.[4] The study aimed to determine if BMS-986322 could reduce inflammation and slow down excessive skin cell growth characteristic of psoriasis.[11]
• Status: The trial was sponsored by Bristol-Myers Squibb and initiated on April 3, 2023.[5] It was completed on August 6, 2024.[1] Various clinical trial registries confirm its completion, with updates as recent as September 10, 2024.[4] Results are expected to be posted on ClinicalTrials.gov when available, though no efficacy or safety data have been publicly released in the accessible materials.[4]
• Locations: The study was conducted internationally, including sites in the US, Canada, Poland, Australia, Japan, and the United Kingdom.[1] Specific research locations included sites in Beverly, MA; Encinitas, CA; and Durham, NC, among others.[11]
• Patient Population: Eligible participants were adults (18 years or older) diagnosed with plaque psoriasis for at least six months, with moderate-to-severe disease activity. They were required to be candidates for phototherapy or systemic therapy and have psoriatic plaques covering 10% or more of their body surface area. Other criteria included a Body Mass Index (BMI) between 18 and 40 kg/m² and a body weight greater than 50 kg. Exclusion criteria included the presence of certain other immune conditions, significant concurrent illnesses, or non-plaque forms of psoriasis.[11]
• Design: Participants were randomized to one of four treatment groups: three different dose levels of BMS-986322 or a placebo.[11]
• Primary Endpoint: According to a review of pipeline agents in psoriasis, the primary endpoint for NCT05730725 was the proportion of participants achieving at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) at 12 weeks. Safety was assessed for up to 16 weeks.[14]

The outcome of this Phase II trial was pivotal. The completion in August 2024 was followed by inquiries from analysts regarding the lack of subsequent progress.[5] Shortly thereafter, BMS indicated the program was stalled and then deprioritized.[5] The absence of publicly disseminated positive results from this key study, coupled with the decision to halt development, strongly suggests that the data did not demonstrate a sufficiently compelling efficacy and safety profile, or a clear differentiation from existing therapies like Sotyktu, to justify advancement into Phase III. Pharmaceutical companies are generally motivated to publicize strongly positive or practice-changing results; the silence surrounding the NCT05730725 outcomes, followed by deprioritization, points towards a dataset that did not meet BMS's internal progression criteria. This observation is also consistent with broader trends where industry-sponsored trials, particularly those with negative or inconclusive findings, may have lower or delayed publication rates.[15]

4.4. Other Investigational Areas

The Bristol Myers Squibb 2023 annual report development portfolio, dated February 2, 2024, listed BMS-986322 as being in Phase I development for "Neuroinflammation Disorders" within the Neuroscience therapeutic area.[3] However, subsequent updates from late 2024 and early 2025, which discuss the completion of the psoriasis trials and the drug's overall deprioritization, make no further mention of ongoing development in neuroinflammation.[1] This omission suggests that the neuroinflammation indication likely did not progress significantly or was also deprioritized, possibly due to failing to meet early endpoints, being deemed less promising than other pipeline assets, or as part of the broader pipeline rationalization that impacted the psoriasis program. Had neuroinflammation represented a viable alternative path forward for BMS-986322, it would likely have been highlighted as a continuing area of focus when the psoriasis indication was discontinued.

Table 2: Overview of Key Clinical Trials for BMS-986322 (Lomedeucitinib)

NCT Identifier	Trial Phase	Indication/Population	Key Objectives	Status (Completion Date)	Sponsor
NCT06088264	Phase I	Healthy Adult Male Participants	Evaluate pharmacokinetics, metabolism, and excretion of [14C] BMS-986322	Completed (Dec 22, 2023)	Bristol Myers Squibb Co.
NCT05615012	Phase I	Healthy Volunteers	Assess drug-drug interaction potential with rosuvastatin, metformin, methotrexate	Completed (Dec 13, 2023)	Bristol Myers Squibb Co.
NCT04175925	Phase I	Healthy Participants	Assess drug levels, drug effects, safety of variable doses; evaluate food and acidity effects	Completed (Results pending on ClinicalTrials.gov)	Bristol Myers Squibb
NCT05730725	Phase II	Participants with Moderate-to-Severe Psoriasis	Evaluate clinical efficacy (PASI 75 at 12 weeks) and safety	Completed (Aug 06, 2024; Results pending on ClinicalTrials.gov)	Bristol Myers Squibb

5. Development Status and Pipeline Prioritization

5.1. Highest Development Phase Achieved

BMS-986322 reached Phase II in its clinical development program, specifically for the indication of moderate-to-severe psoriasis.[1] As of Bristol Myers Squibb's Development Portfolio update in February 2024, the compound was listed under Phase II for this indication.[3]

5.2. Discontinuation/Deprioritization by Bristol Myers Squibb

• Current Status: Despite reaching Phase II, by late 2024 and early 2025, BMS-986322 was confirmed to be "not in development".[5] This statement was made by Dr. Samit Hirawat, Executive Vice President and Chief Medical Officer, Global Drug Development at Bristol Myers Squibb. Corroborating this, drug development databases such as Synapse Patsnap list the highest phase achieved by Lomedeucitinib as "Discontinued Phase 2," with the information last updated in May 2025.[5]
• Rationale Provided by BMS: The primary justification offered by BMS for halting the development of BMS-986322 was a strategic decision to "really focus and prioritize" resources on Sotyktu (deucravacitinib, BMS-986165). Sotyktu is BMS's already approved and marketed TYK2 inhibitor for psoriasis, and the company aims to "maximiz[e] that opportunity from a development and commercial perspective".[5] This decision was made even though BMS-986322 was characterized as a "second-generation TYK2 inhibitor" and had completed its Phase 2 trial in psoriasis in August 2024.[5]
• Context of BMS Cost-Cutting and R&D Productivity Initiatives: The deprioritization of BMS-986322 occurred within the framework of a broader cost-cutting initiative at Bristol Myers Squibb. The company indicated it was "setting a higher bar for investments" in its pipeline and had discontinued other programs as well, such as cendakimab.[5] This suggests that pipeline decisions are heavily influenced by the company's overall financial strategy and efforts to enhance R&D productivity.[17] Consequently, even drug candidates showing some level of promise might not proceed if they fail to meet heightened internal criteria for potential return on investment, strategic alignment, or probability of success within the prevailing financial and strategic landscape of the company.

The decision to deprioritize a "second-generation" TYK2 inhibitor like BMS-986322 in favor of an established "first-generation" product (Sotyktu) underscores a critical aspect of pharmaceutical R&D: market realities and efficient resource allocation can often take precedence over purely scientific pursuits or incremental clinical advancements. Sotyktu represents a known asset with an established market presence and revenue stream for BMS.[3] Developing and launching a second drug in the same therapeutic class, even if it offers some potential advantages, necessitates substantial further investment, complex regulatory navigation, and significant marketing efforts. Furthermore, it could risk cannibalizing the sales of the existing product. BMS's explicit statement about focusing on "maximizing Sotyktu" [5] implies a strategic calculation: the resources that would have been required to advance BMS-986322 were deemed better allocated to expanding Sotyktu's indications, bolstering its market penetration, or investing in other pipeline assets perceived to have a clearer or larger potential return, particularly within a corporate environment focused on cost efficiency.[5] The absence of compelling, publicly shared Phase 2 data for BMS-986322 further supports the inference that its differentiation from Sotyktu was not considered significant enough to justify this new cycle of investment and potential market competition.

6. Therapeutic Context: TYK2 Inhibition in Psoriasis and Other Immune Diseases

6.1. Role of TYK2 in Psoriasis Pathophysiology

Psoriasis is a chronic, immune-mediated inflammatory disease primarily affecting the skin. Its pathogenesis involves a complex interplay of genetic predisposition, environmental triggers, and dysregulation of both innate and adaptive immunity. Cytokines, particularly those belonging to the interleukin-23 (IL-23)/T helper 17 (Th17) cell axis, are central to driving and maintaining psoriatic inflammation.[19] TYK2, as a member of the JAK family, plays a crucial role in mediating the intracellular signaling of several key cytokines implicated in psoriasis. These include IL-23, which is vital for the differentiation, survival, and function of Th17 cells. Th17 cells, in turn, produce pro-inflammatory cytokines like IL-17 and IL-22, which promote keratinocyte proliferation, neutrophil recruitment, and the overall inflammatory cascade observed in psoriatic lesions. TYK2 also transduces signals for Type I interferons (IFNs), which contribute to the inflammatory milieu.[5] Therefore, selective inhibition of TYK2 represents a targeted therapeutic strategy aimed at dampening these critical pro-inflammatory signaling pathways.

6.2. Comparison with other TYK2 inhibitors (e.g., Deucravacitinib/Sotyktu)

Deucravacitinib (BMS-986165, Sotyktu) is Bristol Myers Squibb's first-in-class, FDA-approved oral, selective TYK2 inhibitor. Its selectivity is achieved through a novel allosteric mechanism, binding to the regulatory pseudokinase (JH2) domain of TYK2 rather than the highly conserved ATP-binding site in the kinase (JH1) domain. This unique binding mode allows deucravacitinib to achieve greater selectivity for TYK2 over other JAK family members (JAK1, JAK2, JAK3), thereby minimizing off-target effects associated with less selective JAK inhibitors.5

BMS-986322 was described as a "second-generation TYK2 inhibitor".5 Typically, the term "second-generation" implies an attempt to improve upon earlier compounds in the same class, potentially offering advantages in terms of efficacy, safety, selectivity, pharmacokinetic properties (such as longer half-life or improved bioavailability, possibly through strategies like deuteration), or dosing regimen (e.g., less frequent administration). The specific advantages BMS-986322 was designed to offer over deucravacitinib are not explicitly detailed in the available information. However, the eventual deprioritization of BMS-986322 in favor of continued focus on Sotyktu strongly suggests that any potential advantages observed in early-phase trials were not deemed substantial enough to warrant its continued development, especially considering Sotyktu's established clinical profile, regulatory approval, and market presence.5

6.3. Potential and Challenges of Selective TYK2 Inhibition

The development of selective TYK2 inhibitors holds significant therapeutic potential. By precisely targeting TYK2, these agents aim to modulate specific cytokine pathways known to drive autoimmune diseases like psoriasis, while largely sparing other JAK-mediated pathways essential for normal physiological functions such as hematopoiesis and immune surveillance. This approach offers the prospect of achieving efficacy comparable to biologic therapies but with the convenience of oral administration, and potentially a more favorable safety profile compared to pan-JAK inhibitors, which have been associated with dose-limiting toxicities and black box warnings regarding serious infections, malignancy, and cardiovascular events.[5]

However, the development of selective TYK2 inhibitors also faces challenges. These include the technical difficulty of designing molecules with high selectivity for TYK2 over other highly homologous JAK kinases, particularly if targeting the ATP-binding site. Demonstrating a clinically meaningful superior or differentiated benefit over existing therapies—including other TYK2 inhibitors like deucravacitinib, other oral systemics, or highly effective biologic agents—is a significant hurdle.[5] Navigating an increasingly competitive therapeutic landscape and meeting the high expectations for both efficacy and long-term safety are also critical challenges.

The emergence of selective TYK2 inhibitors like deucravacitinib, and the parallel effort to develop a "second-generation" agent such as BMS-986322, reflects a broader and important trend in immunology drug development. This trend is characterized by a shift towards more targeted kinase inhibition to optimize the benefit-risk profile of new medicines. Pan-JAK inhibitors, while effective, demonstrated that broad immunosuppression can lead to significant safety concerns. This experience created a clear medical need for inhibitors with greater selectivity for individual JAKs, such as TYK2, which are critically involved in specific autoimmune pathways but may have a more limited role in broader physiological processes compared to other JAKs. Deucravacitinib's success as an allosteric, TYK2-selective inhibitor validated this targeted approach.[5] The development of BMS-986322 as a "second-generation" TYK2 inhibitor [5] signified the ongoing endeavor to further refine this selectivity or improve upon other key drug properties (e.g., potency, pharmacokinetics, reduced potential for off-target effects). Although BMS-986322 itself was ultimately deprioritized, the overarching strategy of pursuing isoform-selective JAK inhibitors remains a prominent theme in the field, driven by the aspiration to deliver biologic-like efficacy in an oral formulation coupled with an improved safety margin over older, less selective small molecule immunomodulators.

7. Patents and Intellectual Property

Information from Synapse Patsnap indicates the association of "100 Patents (Medical) associated with Lomedeucitinib," although access to the specific details of these patents requires a subscription to the service.[5] PubChem also provides a link to the WIPO PATENTSCOPE database for patents related to the chemical structure of Lomedeucitinib, identified by its InChIKey: VWIVBQZLVAGLMH-ASGODXDTSA-N.[6]

One patent number, WO2022266444A1, is listed by a commercial supplier in connection with Lomedeucitinib.[9] However, further investigation reveals that this particular patent pertains to "IL-31 MODULATORS FOR TREATING FXR-INDUCED PRURITIS" [21] and is therefore unlikely to be directly related to Lomedeucitinib as a TYK2 inhibitor for psoriasis. Similarly, patent WO2021055652A1 concerns dosage forms for BMS-986165 (deucravacitinib), another TYK2 inhibitor from BMS, and does not specifically mention BMS-986322 or Lomedeucitinib.[22]

A detailed analysis of the patent landscape for BMS-986322 is beyond the scope of the currently available materials, as it would require direct access to patent databases and a thorough review of individual patent claims. Nevertheless, the mention of a significant number of patents associated with Lomedeucitinib [5], even if the exact count is a placeholder, implies that Bristol Myers Squibb likely pursued or secured broad intellectual property (IP) coverage for the compound. Pharmaceutical companies routinely file multiple patents around a promising drug candidate to protect their substantial investment. This IP portfolio can encompass composition of matter patents (covering the molecule itself), process patents (for its synthesis), formulation patents (for specific dosage forms), and method of use patents (for its application in treating particular diseases). Despite the probable existence of such IP protection for BMS-986322, the drug was ultimately deprioritized. This outcome illustrates that robust patent protection alone does not guarantee a drug's progression to market; clinical performance, strategic alignment with corporate goals, and prevailing commercial factors are often the paramount determinants. The value of a drug's patent portfolio diminishes considerably if the drug is not successfully developed and commercialized.

8. Conclusion

BMS-986322 (Lomedeucitinib) is a deuterated, small molecule, selective Tyrosine Kinase 2 (TYK2) inhibitor developed by Bristol Myers Squibb. It was primarily investigated for the treatment of moderate-to-severe psoriasis and progressed through a comprehensive Phase I clinical program into Phase II efficacy and safety studies.

Key findings indicate that despite being positioned as a "second-generation" TYK2 inhibitor, the development of BMS-986322 was deprioritized by BMS. The principal reason cited for this decision was a strategic imperative to focus resources on and maximize the commercial and developmental potential of Sotyktu (deucravacitinib), BMS's already approved and marketed TYK2 inhibitor. This strategic shift occurred within a broader context of R&D pipeline optimization and cost-management initiatives at the company.

Critically, efficacy and safety data from the pivotal Phase II trial in psoriasis (NCT05730725), which completed in August 2024, have not been made publicly available. The absence of positive disclosures, followed by the deprioritization, strongly suggests that the trial results did not demonstrate a sufficiently compelling clinical profile to warrant further investment and progression into Phase III trials, particularly when benchmarked against Sotyktu and the high bar for new entrants in a competitive therapeutic area.

The development trajectory of BMS-986322 serves as an important illustration of the multifaceted and often challenging nature of pharmaceutical R&D. It highlights how scientific potential, clinical trial outcomes, strategic corporate decision-making, and prevailing market dynamics collectively shape the fate of investigational drugs. Even candidates designed with potential optimizations, such as "second-generation" status or specific chemical modifications like deuteration, may not advance if they fail to offer a decisively superior value proposition compared to existing therapies or if they do not align with the evolving strategic and financial priorities of their developers.

9. References

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