MIDATECH PHARMA
R&D | Oncology

Midacore® gold nanoparticles can be chemically decorated with chemotherapeutic or immunotherapeutic agents together with tumour-targeting molecules on the same gold nanoparticle conjugate. Multiple copies of ligands can be attached to enhance affinity. The technology allows highly toxic drugs to be more selectively delivered to tumour cells whilst sparing normal tissue, thereby reducing the side effects associated with chemotherapy and enhancing efficacy.  At present Midatech is focusing its cytotoxic therapeutic programs on development of Midacore® candidates for liver hepatocellular carcinoma (HCC) (MTD119) and brain glioblastoma multiforme (GBM) cancer (MTR103).   

There is currently extensive interest in immune-oncology approaches to the treatment of cancer.  Midacore® gold nanoparticles can be combined with synthetic peptides and small molecule agonists to form gold nanoparticle immunotherapy vaccines.  These small particles can enter immune processing cells and induce cell mediated immune responses against tumor cells.  Pre-clinical programmes utilizing Midacore® vaccines for diffuse intrinsic pontine glioma (DIPG) (MTR111) and glioblastoma (GBM) (MTR116) are approaching key R&D decision points and with positive data are expected to advance into the clinic in 1H 2019.

Q-Sphera sustained drug release technology is being applied to develop a monthly intramuscular depot injection product (MTD201, Q-Octreotide) that is designed to be substitutable with Sandostatin LAR (SLAR) for the management of certain neuroendocrine tumours (NET) and acromegaly.  MTD201 has entered clinical development in a dual endpoint adaptive PK/PD trial that will investigate similarity relative to SLAR.  While designed to be therapeutically equivalent, Midatech believes that the Q-Sphera technology employed for MTD201 will provide significantly improved injection properties.

Midatech’s nano-inclusion technology has been applied to solubilize panobinostat for direct treatment of certain brain cancers (MTX110).  Panobinostat is an established oral anticancer drug but is currently not available in a dosage form that enables its use for treatment of brain cancers.   MTX110 is a highly water-soluble product that has recently entered a clinical trial in children with the rare and devastating brainstem cancer, diffuse intrinsic pontine glioma (DIPG).  MTX110 is being delivered directly to the tumour using convection enhanced delivery (CED).

MTD201 (Q-Octreotide) – Neuro-Endocrine Tumours (NET)

MTD201 (Q-Octreotide) is being developed for the management of neuroendocrine tumours and acromegaly.

Octreotide, formulated as Sandostatin LAR (SLAR) for sustained release, is already available for the treatment of severe diarrhoea and flushing associated with certain neuroendocrine tumours.  It is also used to decrease the production of growth hormone in people suffering from acromegaly who fail to respond to, or are not suitable for surgery. Acromegaly is a rare condition that results from over-production of growth hormone which, if untreated, can cause severe disfigurement and death.

Q-Octreotide is being developed as an alternative to SLAR. Exploiting Midatech Pharma’s Q-Sphera platform, the improved sustained-release formulation used in Q-Octreotide is expected to improve injectability, enabling the use of smaller needles and reducing injection pain compared to SLAR.  Similarly, quicker and simpler product reconstitution is expected to reduce clogging and the time the nurse/physician needs to administer the injection, reducing direct medical costs through decreased administration time and fewer wasted doses.  Midatech Pharma are also investigating the potential shown in preclinical studies, that MTD201 can reduce pharmacokinetic variability, leading to predictable and better controlled outcomes for patients.

A Phase 1 clinical study comparing the pharmacokinetics and surrogate efficacy of Q-Octreotide and Sandostatin LAR is on-going, with data anticipated in 2018.

MTD119 (Hepatocellular Carcinoma)

Liver cancer is the third leading cause of cancer deaths worldwide, affecting approximately 500,000 people.  Prognosis is poor if the tumour cannot be surgically resected, as is the case in up to 80% of patients, with survival typically less than 6 months.  Midacore® drug conjugates are being developed to repurpose and improve the delivery and efficacy of existing chemotherapeutics for liver cancer.

MTD119 is an ‘ultra-small’ gold nanoparticle that carries multiple copies of the highly potent tubulin inhibitor and cytotoxic drug, mertansine, in addition to sugar moieties that enhance uptake of the nanoparticle complex into cancer cells.   After encouraging efficacy data in mouse cancer models, in which MTD119 was shown to enhance uptake of mertansine into tumour cells, the nano-construct is expected to enter formal IND (Investigational New Drug application) enabling studies later in 2018, with completion expected in Q1 2019. An IND submission to the US Food and Drug Administration for ‘first in human’ trials is expected in 2019.

MTX110 (Panobinostat CED) - DIPG

Midatech’s nano-inclusion technology has been applied to solubilize panobinostat for direct treatment of certain brain cancers (MTX110).  Panobinostat is an established oral anticancer drug but is currently not available in a dosage form that enables its use for treatment of brain cancers owing to limitations of poor solubility and poor blood-brain penetrance.   MTX110, a highly water-soluble formulation of panobinostat, has recently entered clinical development in children with the rare and devastating brainstem cancer, diffuse intrinsic pontine glioma (DIPG), at two centres in the United States.  There are currently no approved treatments for DIPG and average survival is just 9 months.  Phase 1 data are expected in 2019.

MTX110 is delivered directly to the brainstem tumour under slight pressure through micro-catheters using convection enhanced delivery (CED).  This emerging delivery technique enables the extent of distribution to the tumour to be visualised in real-time using magnetic resonance imaging to ensure safe and effective delivery to the tumour, and to minimize exposure to healthy brain tissue.

MTX110 has inherent anticancer activity across a number of different brain cancer types in preclinical studies, and therefore has broader potential to be used for the treatment of other cancers that are amenable to CED and other direct delivery methods, including glioblastoma.

MTR103 (Glioblastoma Multiforme, GBM)

Glioblastoma can occur in children and adults and is one of the most aggressive and difficult cancers to manage.  There are limited or no effective treatment options, and available drugs are often associated with significant dose-limiting toxicity. Survival is in the region of 9 to 12 months, and less than 5% or patients survive 5 years.

Midacore® gold nanoparticle drug conjugates are being evaluated in preclinical models for their pharmacokinetic and anti-cancer properties when delivered by Convection Enhanced Delivery (CED).  CED bypasses the blood-brain barrier enabling delivery of therapeutics directly into the tumour via micro-catheters.  The nanoparticle surface is decorated with carbohydrate and other small molecules to encourage retention and enhanced uptake of the drug by cancer cells in the tumour environment (MTR103). 

The MTR103 project is currently in the discovery phase with completion of preclinical proof of concept studies (POC) expected in 2019.

R&D
R&D
Oncology

Midacore® gold nanoparticles can be chemically decorated with chemotherapeutic or immunotherapeutic agents together with tumour-targeting molecules on the same gold nanoparticle conjugate. Multiple copies of ligands can be attached to enhance affinity. The technology allows highly toxic drugs to be more selectively delivered to tumour cells whilst sparing normal tissue, thereby reducing the side effects associated with chemotherapy and enhancing efficacy.  At present Midatech is focusing its cytotoxic therapeutic programs on development of Midacore® candidates for liver hepatocellular carcinoma (HCC) (MTD119) and brain glioblastoma multiforme (GBM) cancer (MTR103).   

There is currently extensive interest in immune-oncology approaches to the treatment of cancer.  Midacore® gold nanoparticles can be combined with synthetic peptides and small molecule agonists to form gold nanoparticle immunotherapy vaccines.  These small particles can enter immune processing cells and induce cell mediated immune responses against tumor cells.  Pre-clinical programmes utilizing Midacore® vaccines for diffuse intrinsic pontine glioma (DIPG) (MTR111) and glioblastoma (GBM) (MTR116) are approaching key R&D decision points and with positive data are expected to advance into the clinic in 1H 2019.

Q-Sphera sustained drug release technology is being applied to develop a monthly intramuscular depot injection product (MTD201, Q-Octreotide) that is designed to be substitutable with Sandostatin LAR (SLAR) for the management of certain neuroendocrine tumours (NET) and acromegaly.  MTD201 has entered clinical development in a dual endpoint adaptive PK/PD trial that will investigate similarity relative to SLAR.  While designed to be therapeutically equivalent, Midatech believes that the Q-Sphera technology employed for MTD201 will provide significantly improved injection properties.

Midatech’s nano-inclusion technology has been applied to solubilize panobinostat for direct treatment of certain brain cancers (MTX110).  Panobinostat is an established oral anticancer drug but is currently not available in a dosage form that enables its use for treatment of brain cancers.   MTX110 is a highly water-soluble product that has recently entered a clinical trial in children with the rare and devastating brainstem cancer, diffuse intrinsic pontine glioma (DIPG).  MTX110 is being delivered directly to the tumour using convection enhanced delivery (CED).

MTD201 (Q-Octreotide) – Neuro-Endocrine Tumours (NET)

MTD201 (Q-Octreotide) is being developed for the management of neuroendocrine tumours and acromegaly.

Octreotide, formulated as Sandostatin LAR (SLAR) for sustained release, is already available for the treatment of severe diarrhoea and flushing associated with certain neuroendocrine tumours.  It is also used to decrease the production of growth hormone in people suffering from acromegaly who fail to respond to, or are not suitable for surgery. Acromegaly is a rare condition that results from over-production of growth hormone which, if untreated, can cause severe disfigurement and death.

Q-Octreotide is being developed as an alternative to SLAR. Exploiting Midatech Pharma’s Q-Sphera platform, the improved sustained-release formulation used in Q-Octreotide is expected to improve injectability, enabling the use of smaller needles and reducing injection pain compared to SLAR.  Similarly, quicker and simpler product reconstitution is expected to reduce clogging and the time the nurse/physician needs to administer the injection, reducing direct medical costs through decreased administration time and fewer wasted doses.  Midatech Pharma are also investigating the potential shown in preclinical studies, that MTD201 can reduce pharmacokinetic variability, leading to predictable and better controlled outcomes for patients.

A Phase 1 clinical study comparing the pharmacokinetics and surrogate efficacy of Q-Octreotide and Sandostatin LAR is on-going, with data anticipated in 2018.

MTD119 (Hepatocellular Carcinoma)

Liver cancer is the third leading cause of cancer deaths worldwide, affecting approximately 500,000 people.  Prognosis is poor if the tumour cannot be surgically resected, as is the case in up to 80% of patients, with survival typically less than 6 months.  Midacore® drug conjugates are being developed to repurpose and improve the delivery and efficacy of existing chemotherapeutics for liver cancer.

MTD119 is an ‘ultra-small’ gold nanoparticle that carries multiple copies of the highly potent tubulin inhibitor and cytotoxic drug, mertansine, in addition to sugar moieties that enhance uptake of the nanoparticle complex into cancer cells.   After encouraging efficacy data in mouse cancer models, in which MTD119 was shown to enhance uptake of mertansine into tumour cells, the nano-construct is expected to enter formal IND (Investigational New Drug application) enabling studies later in 2018, with completion expected in Q1 2019. An IND submission to the US Food and Drug Administration for ‘first in human’ trials is expected in 2019.

MTX110 (Panobinostat CED) - DIPG

Midatech’s nano-inclusion technology has been applied to solubilize panobinostat for direct treatment of certain brain cancers (MTX110).  Panobinostat is an established oral anticancer drug but is currently not available in a dosage form that enables its use for treatment of brain cancers owing to limitations of poor solubility and poor blood-brain penetrance.   MTX110, a highly water-soluble formulation of panobinostat, has recently entered clinical development in children with the rare and devastating brainstem cancer, diffuse intrinsic pontine glioma (DIPG), at two centres in the United States.  There are currently no approved treatments for DIPG and average survival is just 9 months.  Phase 1 data are expected in 2019.

MTX110 is delivered directly to the brainstem tumour under slight pressure through micro-catheters using convection enhanced delivery (CED).  This emerging delivery technique enables the extent of distribution to the tumour to be visualised in real-time using magnetic resonance imaging to ensure safe and effective delivery to the tumour, and to minimize exposure to healthy brain tissue.

MTX110 has inherent anticancer activity across a number of different brain cancer types in preclinical studies, and therefore has broader potential to be used for the treatment of other cancers that are amenable to CED and other direct delivery methods, including glioblastoma.

MTR103 (Glioblastoma Multiforme, GBM)

Glioblastoma can occur in children and adults and is one of the most aggressive and difficult cancers to manage.  There are limited or no effective treatment options, and available drugs are often associated with significant dose-limiting toxicity. Survival is in the region of 9 to 12 months, and less than 5% or patients survive 5 years.

Midacore® gold nanoparticle drug conjugates are being evaluated in preclinical models for their pharmacokinetic and anti-cancer properties when delivered by Convection Enhanced Delivery (CED).  CED bypasses the blood-brain barrier enabling delivery of therapeutics directly into the tumour via micro-catheters.  The nanoparticle surface is decorated with carbohydrate and other small molecules to encourage retention and enhanced uptake of the drug by cancer cells in the tumour environment (MTR103). 

The MTR103 project is currently in the discovery phase with completion of preclinical proof of concept studies (POC) expected in 2019.

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