Lipid Research

 

From fundamental science to clinical trials

Melitherapy

A new pharmaceutical perspective

Melitherapy (short for Membrane-Lipid Therapy) is an innovative scientific platform based on the discovery and rational design of drugs which specifically target lipids of the cell membrane. This contrasts with the usual approach to drug design, which targets proteins to elucidate their structure and then uses molecules (chemicals, antibodies, etc.) that directly regulate their activity.

 

In melitherapy, we use synthetic fatty acids that modify the composition and fluidity of the cell membrane to interfere with the activity of membrane-associated proteins responsible for disease processes, such as tumor growth.

Next-generation medicines

Thanks to this disruptive innovation, we will develop new medicines with an exceptional safety/efficacy combination for serious pathologies where other treatments fail, such as cancer, neurodegenerative or metabolic diseases.

 

Through different clinical trials, we are evaluating the potential translation of significant clinical benefit to patients who receive melitherapy drugs. Study MIN-001-1203 is the first clinical trial with 2-hydroxyoleic (LAM561A1) in patients with advanced solid tumors, including malignant glioma, and it has already been completed with very promising results.

Pathologies

We work on severe diseases with limited treatment options

Our most advanced line of research is for therapies in oncology. Several of our late-stage clinical trials focus on the very promising antitumoral effects of 2-hydroxyoleic acid (LAM561A1) in glioma, brain tumor, in adults and in children.

 

Since our origins in 2006, we have focused on rare, pediatric and geriatric diseases, especially those with unmet medical needs. We are also developing melitherapy drugs for Alzheimer’s disease, and for metabolic, cardiovascular and inflammatory diseases.

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Clinical Trials

MIN-001-1203

A Phase 1/2a Dose Escalation Study of 2-Hydroxyoleic Acid (2-OHOA) in Adult Patients with Advanced Solid Tumours Including Malignant Glioma.

 

EudraCT  #2012-001527-13 – clinicaltrials.gov #NCT01792310

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This trial is an open label, non-randomized study in patients with advanced solid tumours including malignant glioma and consists of two phases: (1) a dose-escalation phase following a standard “3+3” design to establish dose-limiting toxicity (DLT) and a safe dose of 2-OHOA and (2) an expansion phase with two expanded safety cohorts (approximately 10 of whom have malignant glioma and approximately 10 of whom have other advanced solid tumours that are suitable for biopsy) treated at the maximum tolerated dose (MTD). MIN-001-1203 trial has been conducted in leading investigational sites in London, Newcastle, Barcelona, San Sebastian and Bilbao.

Recruitment and treatment of patients in MIN-001-1203 study have completed. A total of 54 patients have been treated, of which 46 are evaluable for safety assessment. 32 patients were recruited in 7 cohorts in the Dose-Escalation Phase and 22 patients in two safety expansion cohorts in the expanded phase. Results of the study are currently being evaluated and have confirmed an excellent safety profile, while promising clinical activity (by RANO / RECIST v1.1) has been reported in several cases, including patients with recurrent malignant glioma.

MIN-002-1801

A Phase 1b Dose Finding Study of the Safety of 2-Hydroxyoleic Acid Sodium Salt (2-OHOA) Administered Orally in Combination with Temozolomide and Radiation Therapy (Concurrent Phase) or Temozolomide Alone (Maintenance Phase) in the First Line Treatment of Subjects with Glioblastoma.

 

EudraCT #2018-000317-21 – clinicaltrials.gov #NCT03867123

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First-line treatment for patients with GBM consists of a concurrent phase (one 6-week cycle with daily administration of temozolomide (TMZ)) during which TMZ is given with Radiation Therapy (RT), followed by a rest phase (4 weeks in duration;), and a maintenance phase, during which patients receive TMZ for up to six 28-day cycles. The purpose of this study is to determine the highest safe dose of 2-OHOA administered orally in combination with temozolomide (TMZ) and radiation therapy (RT) during the concurrent phase, and in combination with TMZ alone during the maintenance phase. This study has been successfully executed in 3 hospitals in Spain without any adverse event due to 2-OHOA treatment.

MIN-001P-1501

A Phase 1/2a Study of 2-Hydroxyoleic Acid in Pediatric Patients with Malignant Glioma and Other Advanced Solid Tumors.

 

EudraCT #2018‐000365‐37 – clinicaltrials.gov: #NCT04299191

More information

An open label, non-randomized study in pediatric patients with advanced high-grade gliomas and other solid tumors. The study will be performed in two phases – a dose escalation phase in up to 18 patients following a standard “3+3” design to establish dose limiting toxicity (DLT) and a “safe” dose of 2-OHOA followed by an expanded safety cohort of up to 10 patients treated at the MTD. If the MTD is well tolerated in the expanded safety cohort, that dose becomes the RP2D.

IND approved. Patient recruitment opened in the USA leaded by the pediatric clinical research institution Hackensack UMC, NJ.

MIN-003-1806

A Phase 2b/3, Randomized, Double-Blind, Adaptive, Placebo-Controlled Adjuvant Trial in Newly Diagnosed Glioblastoma (NDGBM) Patients to Assess the Efficacy and Safety of 2-Hydroxyoleic Acid (LAM561) in Combination with Radiotherapy and Temozolomide Standard of Care Treatment.

EUdraCT #2012-001527-13 – clinicaltrials.gov: #NCT04250922

More information

This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1 ratio), adjuvant trial to assess the efficacy and safety of 2-hydroxyoleic acid (LAM561) versus placebo in patients with newly diagnosed GBM IDH wildtype. In both arms, patients will receive the SoC and will be randomized to receive either placebo (Arm A) or 2-OHOA (Arm B).

PIIB Protocol design and regulatory strategy agreed with EMA (Sep. 2018) CTA process ongoing in IL, SP, FR, UK, IT & NL. Up to 25 sites planned to recruit patients as of Q1 2019.

Expanded Access Policy

Laminar Pharmaceuticals is a pioneering biopharmaceutical company, focused on the discovery, rational design and initial clinical development of drugs to treat oncological and other pathologies. All our compounds are based on a novel therapeutic approach: Membrane Lipid Therapy (MLT), or melitherapy for short. We are a science-driven company committed to putting patients first. Our goal is to provide access to our investigational therapies at the appropriate time and in the correct manner for patients. 

Clinical trials and the generation of safety and efficacy data are the most appropriate and effective way of ensuring objective review and decision making by concerned Regulatory Authorities (eg. FDA, EMA, or national competent regulatory agencies). This process ultimately provides access to innovative and new, effective and well-tolerated approved medicines for patients.

Laminar Pharmaceuticals understands that some patients may wish to access investigational medicines that are not yet approved by the regulatory authorities. The most appropriate way for patients to access our investigational products is by participating in our clinical trials, which are managed by a team of independent medical and clinical experts and are specifically designed to determine the safety and efficacy of the investigational products so that their clinical benefits and risks can be adequately understood, and to ensure that quality of life improvements or effects compared to existing therapies can be considered against any potential adverse effects. Patients who are interested in participating in one of our studies are encouraged to discuss their specific needs with their physician. Information regarding our ongoing clinical trials can be accessed at www.clinicaltrials.gov or in our website www.laminarpharma.com/lipid-research_/#clini.

Expanded Access, also called compassionate use or early access, enables some patients with serious or life-threatening diseases without available therapeutic alternatives, who would not have otherwise met the enrollment criteria for the clinical trials in progress, to gain access to investigational treatment outside of a clinical trial. Expanded access is different from a clinical trial in which the primary purpose is to collect extensive safety and efficacy data to support submission of an application to the FDA, EMA, or similar regulatory agencies, to market a drug.

Laminar Pharmaceuticals understands there might be patients interested in obtaining access to our investigational products for treatment under an Expanded Access program. However, at this stage of the development of our products we are unable to manufacture our investigational drugs in the quantities that may be needed for expanded access purposes. Therefore, to ensure availability of investigational material for clinical research and to maintain the safety of potential patients, Laminar Pharma does not currently provide access to our investigational products through Compassionate use/Expanded Access.

This policy may be revised by Laminar Pharmaceuticals at any time. Should you have additional questions, please reach out to your physician, or contact clinical.dev@laminarpharma.com.

Collaborations

Scientific partnerships with leading research institutions and hospitals

We currently head a consortium of 12 leading clinical and research institutions from across Europe in the CLINGLIO project, designed to test the efficacy and safety of our most promising anticancer drug, LAM561 (2OHOA). Our goal is to execute “A Clinical Phase IIB trial with 2OHOA in patients with newly-diagnosed malignant glioma”, and to this end we have been awarded a 6,15 million euro grant by the European Commission. Find out more at the CLINGLIO project website. We are also working with the Fundación Rioja Salud, in Spain.

Current Public Funding

This research is supported by:

  • European Commission H2020 Framework Programme (agreement number 755179 and 101033275)

  • Spanish Ministerio de Economía y Competitividad and European Regional Development Fund (grant numbers RTC-2015- 3542 and RTC-2015-4094)

  • Spanish research agency (Grants DI-14-06701 and DI-17-09187)

  • Spanish Ministerio de Ciencia e Innovación (grant numbers RTC-2019-007399-1)

logo Ministerio de Ciencia e Innovación

  • Balearic Island Government and European Regional Development Fund (grants number ES01/TCAI/53_2016; PROCOE/5/2017; ES01/TCAI/21_2017 and ES01/BT/21)

  • Balearic Island Government and European Social Fund (grants number PD/036/2016; FPI/1981/2016; FPI/2063/2017; FPI/2177/2018; FPI_063_2020 and PD/058/2020)

Papers

READ OUR PUBLISHED RESEARCH

2020 – Torres, M., Rosselló, C. A., Fernández-García, P., Lladó, V., Kakhlon, O., & Escribá, P. V.  International Journal of Molecular Sciences21(7), 2322.

2020 – Parets, S., Irigoyen, Á., Ordinas, M., Cabot, J., Miralles, M., Arbona, L., Péter, M., Balogh, G., Fernández-García, P., Busquets, X. and Lladó, V.  Frontiers in Cell and Developmental Biology8, 164.

2019 – Massalha, W., Markovits, M., Pichinuk, E., Feinstein-Rotkopf, Y., Tarshish, M., Mishra, K., Llado, V., Weil, M., Escriba, P.V. and Kakhlon, O. Bioscience reports39(1).

2019 – Paula Fernández-García, Catalina A. Rosselló, Raquel Rodríguez-Lorca, Roberto Beteta-Göbel, Javier Fernández-Díaz, Victoria Lladó, Xavier Busquets and Pablo V. Escribá. Cancers 201911, 88

2017 – Ugidos, I. F., Pérez-Rodríguez, D., & Fernández-López, A. Neural regeneration research12(8), 1273.

2017 – Ugidos, I.F., Santos-Galdiano, M., Pérez-Rodríguez, D., Anuncibay-Soto, B., Font-Belmonte, E., López, D.J., Ibarguren, M., Busquets, X. and Fernández-López, A. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1859(9), 1648-1656.

2017 – Mohaibes, R.J., Fiol-deRoque, M.A., Torres, M., Ordinas, M., López, D.J., Castro, J.A., Escribá, P.V. and Busquets, X. Biochimica et Biophysica Acta (BBA)-Biomembranes1859(9), 1596-1603.

2017 – Casas, J., Ibarguren, M., Álvarez, R., Terés, S., Lladó, V., Piotto, S.P., Concilio, S., Busquets, X., López, D.J. and Escriba, P.V. Biochimica et Biophysica Acta (BBA)-Biomembranes1859(9), 1526-1535.

2017 – Noguera-Salvà, M.A., Guardiola-Serrano, F., Martin, M.L., Marcilla-Etxenike, A., Bergo, M.O., Busquets, X. and Escribá, P.V. Biochimica et Biophysica Acta (BBA)-Biomembranes1859(9), 1536-1547.

2015 – Álvarez, R., López, D.J., Casas, J., Lladó, V., Higuera, M., Nagy, T., Barceló, M., Busquets, X. and Escribá, P.V. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids1851(11), 1511-1520.

MORE DOCUMENTS

2016 – Manuel Torres et al. Update on Dementia. Chapter 7. Dr. Davide Moretti (Ed.) Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease. InTech, DOI: 10.5772/64757

2017 – Escriba PV. Membrane-lipid therapy: A historical perspective of membrane-targeted therapies – From lipid bilayer structure to the pathophysiological regulation of cells.Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt B):1493-1506. doi: 10.1016

2015 – Escribá PV, Busquets X, Inokuchi JI, Balogh G, Török Z, Horváth I, Harwood JL, Vígh L.Membrane lipid therapy: Modulation of the cell membrane composition and structure as a molecular base for drug discovery and new disease treatment. . Prog Lipid Res. 2015 May 9;59:38-53. Review.

2015 – Torres M, Marcilla-Etxenike A, Fiol-deRoque MA, Escribá PV, Busquets X. Apoptosis. 2015 May; 20(5):712-24

2015 – G. Avila-Martin, I. Galan-Arriero, A. Ferrer-Donato, X. Busquets, J. Gomez-Soriano, P.V. Escribá, J. Taylor. Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury. Eur J Pain. 2015 Jan;19(1):111-22.

2014 – Fernández R, Lage S, Abad-García B, Barceló-Coblijn G, Terés S, López DH, Guardiola-Serrano F, Martín ML, Escribá PV, Fernández JA. Analysis of the lipidome of xenografts using MALDI-IMS and UHPLC-ESI-QTOF. J Am Soc Mass Spectrom. 2014 Jul;25(7):1237-46

2014 – Escribá, P.V. and Nicolson, G.L. Biochimica et biophysica acta1838(6), 1449.

2014 – Lladó, V., López, D.J., Ibarguren, M., Alonso, M., Soriano, J.B., Escribá, P.V. and Busquets, X. Biochimica et Biophysica Acta (BBA)-Biomembranes1838(6), 1619-1627.

Study posters

Resources

Science communication materials for everyone

Do you want to know how melitherapy works? We have made an animation video and a series of infographics with clear illustrations and straightforward explanations of this fascinating science.

Feel free to download and share these educational materials, or even republish them — without alteration and with appropriate credit to Laminar Pharma, please!