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EP4486308A1 - Composés thérapeutiques, formulations et leur utilisation - Google Patents

Composés thérapeutiques, formulations et leur utilisation

Info

Publication number
EP4486308A1
EP4486308A1 EP23713555.3A EP23713555A EP4486308A1 EP 4486308 A1 EP4486308 A1 EP 4486308A1 EP 23713555 A EP23713555 A EP 23713555A EP 4486308 A1 EP4486308 A1 EP 4486308A1
Authority
EP
European Patent Office
Prior art keywords
composition
solid amorphous
cancer
amorphous dispersion
dispersion
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23713555.3A
Other languages
German (de)
English (en)
Inventor
Imran ALIBHAI
Sofia De Achaval
Ralph CARICOFE
JR. L. Graham WHITESELL
Ian Smart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tvardi Therapeutics Inc
Original Assignee
Tvardi Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tvardi Therapeutics Inc filed Critical Tvardi Therapeutics Inc
Publication of EP4486308A1 publication Critical patent/EP4486308A1/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • solid amorphous dispersions comprising a compound of Formula (I) and a polymer excipient
  • methods of making said dispersions compositions comprising said dispersions, oral dosage forms comprising said compositions, as well as methods of treating diseases or disorders (e.g., cancer, fibrosis, inflammatory diseases or disorders) comprising administering oral dosage forms comprising said compositions.
  • diseases or disorders e.g., cancer, fibrosis, inflammatory diseases or disorders
  • solid amorphous dispersions comprising: a) a compound of formula (I): or a pharmaceutically acceptable salt thereof; and b) a polymer excipient.
  • solid amorphous dispersions comprising: a) a compound of formula (I):
  • solid amorphous dispersions comprising: a) at least 150 mg of a compound of formula (I): or a pharmaceutically acceptable salt thereof; and b) a polymer excipient.
  • compositions comprising: a) a solid amorphous dispersion comprising: i) at least 150 mg of a compound of formula (I):
  • solid oral dosage forms comprising a compound of formula (I).
  • FIG. 1 shows the kinetic solubility of TTI-101 compositions with 10%, 15%, or 25% CIP in FaSSIF (pH 6.5) monitored for 6 hours.
  • the present disclosure in part, provides solid amorphous dispersions comprising a compound of Formula (I) and a polymer excipient, methods of making said dispersions, compositions comprising said dispersions, oral dosage forms comprising said compositions, as well as methods of treating diseases or disorders (e.g., cancer, fibrosis, inflammatory diseases or disorders) comprising administering oral dosage forms comprising said compositions.
  • diseases or disorders e.g., cancer, fibrosis, inflammatory diseases or disorders
  • salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, di gluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy- ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pec
  • Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N + (Ci-4alkyl)4 salts.
  • Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like.
  • Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.
  • oral dosage form refers to a pharmaceutical composition that has been formulated or otherwise prepared for oral administration, such as in a discrete form.
  • a “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle-aged adult or senior adult)) and/or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and/or dogs.
  • the subject is a human.
  • the subject is a non- human animal.
  • the terms “human,” “patient,” “subject,” and “individual” are used interchangeably herein. None of these terms require the active supervision of medical personnel.
  • the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or reverses or slows the progression of the disease, disorder or condition (also “therapeutic treatment”).
  • the “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response.
  • the effective amount of a compound of the invention may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject.
  • a “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit (e.g., treating, preventing, and/or ameliorating cancer in a subject, or inhibiting protein-protein interactions mediated by an SH2 domain in a subject, at a reasonable benefit/risk ratio applicable to any medical treatment) in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.
  • a therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the disease, disorder or condition.
  • the term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent.
  • a “prophylactically effective amount” of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or prevent its recurrence.
  • a prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease, disorder or condition.
  • the term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent.
  • a “prophylactic treatment” contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition.
  • compositions Compositions, Formulations, Oral Dosage Forms
  • the compound of Formula (I) (also referred to as TTI-101) is highly insoluble (“brick dust”). It is insoluble in aqueous solutions and has relatively low solubility in most solvents. Furthermore, the compound of Formula (I) has a crystalline structure with high crystal-lattice energy, contributing to rapid precipitation or crystallization of the compound from solution. Its low solubility and high crystallinity have contributed to various difficulties in preparing formulations that are suitable for administration in human subjects. Current formulations are liquid formulations delivered via capsules.
  • a formulation of the compound of formula (I) dissolved in 60:40 Labrasol®/PEG400 and encapsulated into a hard gelatin capsule (unit dose: 36 mg), while showing encouraging results in 3 dose cohorts, was prevented from advancing to a fourth patient cohort (25.6 mg/kg/day as 12.8 mg/kg twice daily (BID) doses) because of an unacceptably high pill burden.
  • a 70 kg subject in Cohort 4 would require 60 capsules per day split into BID doses.
  • Other oral dosage forms comprising the compound of formula (I) (e.g., as a self-emulsifying drug dispersion, e.g., comprising Kolliphor® RH 40 (PEG-40 hydrogenated castor oil), PEG600, Polysorbate 20, Labrasol®, and citric acid) are able to reduce pill burden compared to the two-component system (e.g., 60 capsules per day of the two-component system to 22 capsules per day in the same Cohort 4 with the self-emulsifying drug dispersion); however, such formulations still have limited drug loading per single oral dosage form and may require, for example, refrigerated (e.g., 2-8 °C) storage conditions.
  • a self-emulsifying drug dispersion e.g., comprising Kolliphor® RH 40 (PEG-40 hydrogenated castor oil), PEG600, Polysorbate 20, Labrasol®, and citric acid
  • Kolliphor® RH 40 PEG-40 hydrogenated castor oil
  • PEG600
  • solid oral dosage forms comprising a solid amorphous dispersion comprising a compound of Formula (I):
  • a pharmaceutically acceptable excipient that provide high loading of a compound of Formula (I), good ability to provide for high bioavailability of a compound of Formula (I), good stability (e.g., chemical and/or physical stability), and/or reduce pill burden for individuals receiving therapies involving the administration of a compound of Formula (I).
  • excipient or combination of excipients disclosed herein provide(s) improved solubility of a compound of Formula (I), improved physical stability (e.g., low crystallinity, good solubility and/or dispersion of a compound of Formula (I)), improved chemical stability of a compound of Formula (I), improved (e.g., oral) bioavailability of a compound of Formula (I), no leakage of any liquid (e.g., as compared to banded capsules), longer shelf life, favorable storage conditions (e.g., improved storage conditions of the compositions, formulations, and oral dosage forms at ambient conditions, e.g., requiring less protection from oxygenation and/or humidity), and/or desirable or therapeutic effect, with a manageable (e.g., fewer than 10 pills per day (e.g., 8 pills or fewer per day), or other amount described herein) and/or reduced pill burden (e.g., relative to two component excipient systems described herein and self-emulsifying drug dis
  • the excipient or combination of excipients is/are suitable for maintaining or stabilizing the compound of Formula (I) in an amorphous state (e.g., as a stabilized amorphous dispersion).
  • the compositions disclosed herein reduce or prevent the crystallization of the compound of Formula (I) when the compound is released in the gastrointestinal (GI) tract.
  • the dispersions, compositions, and oral dosage forms described herein comprise a compound of Formula (I) as a pharmaceutically acceptable salt, a hydrate, or a solvate.
  • a composition disclosed herein is set forth as in Table 1 (e.g., wherein the total wt. % in the composition does not exceed 100%).
  • the solid amorphous dispersions described herein are prepared using spray- dried dispersion (SDD) technique.
  • SDD produces a single-phase, amorphous molecular dispersion (a solid solution) of the API in a polymer matrix.
  • SDDs are obtained by dissolving an API (e.g., TTI-101) and a polymer excipient(s) in a solvent(s) and then spray drying the solution.
  • the solid amorphous dispersions prepared using spray- dried dispersion (SDD) techniques described herein provide for reduced pill burden.
  • formulations described herein prepared using the SDD technique results in reduced pill burden compared to a formulation prepared using a self-emulsifying drug dispersion (SEDD) technique.
  • SEDD self-emulsifying drug dispersion
  • three times as many pills prepared using the SEDD technique e.g., Formulation 2
  • a formulation prepared using the SDD technique e.g., Formulation 3
  • a number of pills needed of Formulation 3 is 15 pills or fewer.
  • a number of pills needed of Formulation 3 is 10 pills or fewer.
  • a number of pills needed of Formulation 3 is 8 pills or fewer. In some embodiments, a number of pills prepared by the methods described herein is 6 pills or fewer. In some embodiments, a number of pills needed of Formulation 3 is 4 pills or fewer. In some embodiments, a number of pills needed of Formulation 3 is 3 pills or fewer. In some embodiments, a number of pills needed of Formulation 3 is 2 pills or fewer. [00034] In some embodiments, formulations described herein prepared using the SDD technique (e.g., Formulation 3) lowers the pill burden required to achieve a therapeutic dose of TTI-101 as compared to a formulation prepared using the SEDD technique (e.g., Formulation 2) or Formulation 1.
  • the solid amorphous dispersion comprises about 70% w/w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 75% w/w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 80% w/w of the polymer excipient.
  • the composition comprises about 15% w/w to about 40% w/w of the compound of formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 20% w/w to about 40% w/w of the compound of formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 5% w/w to about 30% w/w of the compound of formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 10% w/w to about 30% w/w of the compound of formula (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the composition comprises about 20% w/w to about 35% w/w of the compound of formula (I), or a pharmaceutically acceptable salt thereof.
  • Tablets may be plain, film, sugar coated, bisected, embossed, layered, and/or sustained-release. They can be made in a variety of sizes, shapes, and colors. Tablets may be swallowed, chewed, or dissolved in the buccal cavity or beneath the tongue.
  • the fibrotic disease/disorder is fibrosis following exposure to certain drugs such as chemotherapy, fibrosis following exposure to environmental or other toxins or allergens, fibrosis occurring after an ischemia/reperfusion injury such as myocardial infarction or hypotension, fibrosis occurring after radiation, fibrosis following hepatitis induced by alcohol, toxins, drugs or infections, primary biliary cirrhosis, fibrosis following viral infections involving the heart, liver, or lung, and/or idiopathic retroperitoneal fibrosis.
  • drugs such as chemotherapy, fibrosis following exposure to environmental or other toxins or allergens, fibrosis occurring after an ischemia/reperfusion injury such as myocardial infarction or hypotension, fibrosis occurring after radiation, fibrosis following hepatitis induced by alcohol, toxins, drugs or infections, primary biliary cirrhosis, fibrosis following viral infections involving the heart, liver, or lung, and
  • graft-versus-host diseases pulmonary lymphangioleiomyomatosis, chagasic cardiomyopathy, age-related macular degeneration, amyloidosis, astrogliosis in Alzheimer’s or other neurodegenerative diseases, or familial amyloid polyneuropathy.
  • the neurodegenerative disease is chemotherapy -induced peripheral neuropathy, diabetic neuropathy, or chemobrain.
  • methods of treating, preventing, or reducing the risk or severity of pain in an individual in need thereof the method comprising administering to the individual any composition or oral dosage described herein.
  • pain is neuropathic pain.
  • the method comprising administering to the individual any composition or oral dosage described herein.
  • the insulin resistance is a result of an underlying condition.
  • the insulin resistance is associated with muscle of the individual being treated.
  • the insulin resistance is caused by any reason for the individual, such as elevated free fatty acids in the blood, obesity, being overweight, having visceral fat, having a high fructose intake, having inflammation, being inactive, dysbiosis of the gut microbiota, and/or being genetically predisposed.
  • the pill burden discussed herein is associated with any suitable therapeutic (e.g., daily) dose of compound of Formula (I) and/or loading of compound of Formula (I) in the oral dosage form(s), such as any dose or amount described herein.
  • the method comprises administering at least 1 mg/kg/day of the compound of formula (I) to the individual. In certain embodiments, the method comprises administering at least 10 mg/kg/day of the compound of formula (I) to the individual. In certain embodiments, the method comprises administering at least 20 mg/kg/day of the compound of formula (I) to the individual. In certain embodiments, the method comprises administering at least 25 mg/kg/day of the compound of formula (I) to the individual.
  • a number of adverse events is reduced with SDD formulations as compared to SEDD formulations.
  • the severity of adverse events is reduced with the SDD formulations as compared to the SEDD formulations.
  • a number of individuals experiencing an adverse event is reduced with the SDD formulations as compared to the SEDD formulations.
  • the adverse event is diarrhea.
  • LPS Liquid-liquid phase separation
  • HPMC AS-LG/HPMC-E3 +/- 5% w/w surfactants and HPMAC AS-LG +/-5% w/w surfactants were prepared and evaluated with LLPS.
  • Surfactants used in this study include: Poloxamer 188, Poloxamer 407, Kolliphor RH40, and vitamin E TPGS. Addition of the poloxamer 407, Kolliphor RH40 and vitamin E TPGS provided marginal improvement in LLPS performance for the mixture of HPMC AS-LG / HPMC-E3.
  • TTI-101 Particle size reduction for TTI-101 by micronization and nano-milling provided poor bioavailability (e.g., 10-20 times lower bioavailability than a solution of TTI- 101).
  • Hot melt extrusion HME was used and the resulting dispersions were evaluated using DSC miscibility, DSC extrudability and rheology studies. Polymer systems tried include: Soluplus; Soluplus + Kolliphor RH40; Soluplus + Vitamin E TPGS; and PVPVA64 + Kolliphor RH40.
  • Dispersions of TTI-101 made using HME showed high TTI-101 degradation and performance in biorelevant in-vitro super-saturated kinetic dissolution.
  • compositions comprising TTI-101.
  • Exemplary SDD compositions were prepared with the polymer system and concentration of TTI-101 as shown in Table 4.
  • compositions 1-5 exhibited marginal performance in super-saturated kinetic dissolution (SSKD). Characterization of compositions 1-5 showed that they were not fully amorphous. On the other hand, compositions 6-10 were fully amorphous. Addition of a crystallization inhibiting polymer (CIP) such as HPMC AS-LG to the compositions improved peak concentration and supersaturation of TTI-101. Compositions 11 and 12 exhibited good stability while composition 13 exhibited two glass transition temperatures (Tg’s) indicating phase separation in the SDD and also showed TTI-101 crystallization during the stability assessment. Composition 14 showed changes in Tg during stability assessment and compositions 15 and 16 exhibited two Tg’s indicating a phase separation in the SDD.
  • CIP crystallization inhibiting polymer
  • CIPs that were used include: MC-A4M, HPMC-E4M, and HPMC-K4M.
  • Compositions with MC-A4M performed similarly to the compositions with HPMC AS-LG as the CIP.
  • Antioxidants such as citric acid, ascorbic acid, or ascorbyl palmitate (each 1% w/w) were added to the SDD compositions of TTI-101 with HPMC AS-LG or Eudragit L100-55.
  • the resulting compositions exhibited changes in Tg during stability assessment and provided marginal improvements in chemical stability of the SDD-based compositions.
  • CIPs were added to the SDD compositions of TTI-101 with HPMC AS-LG or Eudragit L100-55.
  • CIPs that were screened include: HPMC AS-LG, MC-A4M, HPMC-E4M, and HPMC-K4M.
  • Compositions with MC-A4M performed similarly to the compositions with HPMC AS-LG as the CIP.
  • HPMC AS-LG concentrations were: 10%, 15% and 25 %w/w (ratio of HPMC AS-LG (CIP) to SDD.
  • the composition with 25 % w/w HPMC AS- LG to SDD showed highest TTI-101 concentration and a steady rise in TTI-101 with no drop in the concentration throughout the run (6 hours) (FIG. 1).
  • An exemplary tablet formulation was prepared with a SDD of TTI-101 and methacrylic acid and ethyl acrylate copolymer as the polymer excipient (Table 5).
  • the formulation was mixed, roller compacted (RC), milled, blended, compressed and coated with a film to form an exemplary tablet.
  • Intra and extra-granular components were added to improve processability of roller compaction, tablet compression, and film coating.
  • Formulations A-D were prepared according to Tables 6- 7.
  • Formulation E was prepared according to the methods described in WO2021150912.
  • Table 8 shows exemplary dosages of TTI-101 administered to rats and %TTI- 101 in each formulation.
  • Formulation F (IV) was prepared in DMSO/EtOH/PEG400/Saline at 5/2/43/50 %v/v (TTI-101 5 mg/mL).
  • the absolute oral bioavailability compared to Formulation F for the oral formulations were 0.183, 0.156, 0.229, 0.139, and 0.173, respectively for Formulations A-E.
  • the Cmax was: Formulation F (77000 ng/mL), Formulation E (10300 ng/mL), Formulation C (5500 ng/mL), Formulation D (4490 ng/mL), Formulation A (4060 ng/mL), and Formulation B (3500 ng/mL).
  • the AUClast was Formulation F (188000 h*ng/mL), Formulation C (41800 h*ng/mL), Formulation E (31400 h*ng/mL), Formulation A (30700 h*ng/mL), Formulation B (28600 h*ng/mL), and Formulation D (25800 h*ng/mL).
  • composition 7 of Example 2 with a CIP such as HPMC AS LF showed higher bioavailability to a capsule formulation (Formulation E) of TTI-101
  • a formulation comprising composition 7 of Example 2 with a CIP such as HPMC AS LG showed similar bioavailability to Formulation E of TTI-101
  • Formulation E is a capsule formulation comprising 80 mg of TTI-101
  • exemplary tablet formulations described herein comprises 200 mg TTI- 101.
  • TTI-101 was assessed in patients with advanced cancers.
  • TTI-101 was assessed in healthy volunteers.
  • Formulations 1-3 were prepared as in the previous examples. Two trials were performed. The first trial was performed similar to the trial outlined below in Table 9 (for patients with advanced cancers) and was made up of a first cohort of subjects receiving Formulation 1, a second cohort of subjects receiving Formulation 2, and a third cohort of subjects receiving Formulation 3. The second trial was similar to the trial outlined below in Table 10 (for healthy volunteers) and was made up of a cohort of subjects receiving Formulation 3.
  • Formulation 3 (prepared by the SDD technique) lowers the pill burden required to achieve a therapeutic dose of TTI-101.
  • Formulation 3 can deliver 200 mg of TTI-101 per unit versus 80 mg of TTI-101 per unit when Formulation 2 is used and 30 mg of TTI-101 per unit when Formulation I is used.
  • Formulation 3 has reduced rate and severity of treatment emergent adverse events, and has similar exposures to Formulation

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des dispersions amorphes solides, des compositions et des formes posologiques orales solides comprenant un composé de formule (I). Dans des exemples spécifiques, de telles compositions comprennent un excipient polymère, et éventuellement un polymère inhibiteur de cristallisation. Dans certains exemples, de telles compositions sont utiles pour le traitement de la fibrose, du cancer et/ou d'une maladie/d'un trouble inflammatoire.
EP23713555.3A 2022-03-01 2023-03-01 Composés thérapeutiques, formulations et leur utilisation Pending EP4486308A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263268723P 2022-03-01 2022-03-01
PCT/US2023/063520 WO2023168295A1 (fr) 2022-03-01 2023-03-01 Composés thérapeutiques, formulations et leur utilisation

Publications (1)

Publication Number Publication Date
EP4486308A1 true EP4486308A1 (fr) 2025-01-08

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP23713555.3A Pending EP4486308A1 (fr) 2022-03-01 2023-03-01 Composés thérapeutiques, formulations et leur utilisation

Country Status (11)

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EP (1) EP4486308A1 (fr)
JP (1) JP2025506890A (fr)
KR (1) KR20240152398A (fr)
CN (1) CN119136790A (fr)
AR (1) AR128676A1 (fr)
AU (1) AU2023227540A1 (fr)
CA (1) CA3245018A1 (fr)
IL (1) IL315222A (fr)
MX (1) MX2024010568A (fr)
TW (1) TW202341973A (fr)
WO (1) WO2023168295A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023244946A1 (fr) 2022-06-15 2023-12-21 Tvardi Therapeutics, Inc. Promédicaments d'inhibiteurs de stat3
WO2025054280A1 (fr) * 2023-09-05 2025-03-13 Tvardi Therapeutics, Inc. Formulations d'inhibiteurs de stat3 et leurs méthodes d'utilisation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3021839B1 (fr) * 2013-07-18 2021-06-23 Baylor College Of Medicine Compositions pour le traitement de la fibrose
SG11202010347XA (en) * 2018-04-19 2020-11-27 Tvardi Therapeutics Inc Stat3 inhibitors
TW202139984A (zh) * 2020-01-24 2021-11-01 美商特梵迪治療股份有限公司 治療性化合物及其調配物與用途

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CN119136790A (zh) 2024-12-13
CA3245018A1 (fr) 2023-09-07
AR128676A1 (es) 2024-06-05
KR20240152398A (ko) 2024-10-21
TW202341973A (zh) 2023-11-01
JP2025506890A (ja) 2025-03-13
AU2023227540A1 (en) 2024-09-12
MX2024010568A (es) 2024-09-06
IL315222A (en) 2024-10-01
WO2023168295A1 (fr) 2023-09-07

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