Phase II Dose Confirmed and Encouraging Survival Data
Midatech Pharma PLC (AIM: MTPH.L; Nasdaq: MTP), an R&D biotechnology company focused on improving the bio‐delivery
and biodistribution of medicines, is pleased to announce encouraging headline results from a Phase I study at the
University of California, San Francisco ("UCSF") in patients with Diffuse Intrinsic Pontine Glioma ("DIPG") (the "UCSF study"
The primary endpoint of the study was to determine the dosage regimen to be used in a proposed Phase II study of the
safety and efficacy of MTX110 in patients with DIPG. Preliminary high‐level data from the UCSF study supports a dose of
between 60μM and 90μM of MTX110, depending upon patient tolerance over the course of 12 infusions in Phase II.
In total, seven patients were recruited into the UCSF study. Patients were newly diagnosed with DIPG and received focal
external beam radiation therapy four to 14 weeks before commencement of MTX110 treatment. Eligibility required a
pontine location of the tumour with diffuse involvement of at least two thirds of the pons and no evidence of metastatic
disease. Patients were not excluded by total tumour volume. MTX110 was administered directly into the tumour via a
micro‐catheter using convection enhanced delivery ("CED") with gadolinium‐enhanced intra‐operative MRI to guide and
track drug distribution to the tumour. Patients could receive up to 12 cycles of treatment every four to eight weeks. The
dose was escalated between and within patients as tolerated initially by increasing the infusion volume at a concentration
of 30μM MTX110 and then with higher drug concentrations of 60μM and 90μM as the sixth and seventh dose increments,
At the interim cut‐off date (30 September 2020), median overall survival based on Kaplan Meier analysis was 26.06 months
(CI 11.3 ‐ 26.06 months) and overall survival at 12 months (OS12) was 71.4% (five of seven patients alive). Three patients
remain alive and continue to be monitored. Survival was not an endpoint of the UCSF study nor was the study powered for
statistical significance and therefore no conclusions as to the impact of MTX110 on overall survival rates can be drawn from
The proposed Phase II trial is expected to evaluate overall survival at 12 months as the primary endpoint in 19 evaluable
patients. The planned design is single arm and statistically powered for comparisons with defined historical survival data.
MTX110 is expected to be delivered using an alternative CED catheter system that enables regular drug infusions directly
into the tumour without a need for repeated surgery.
DIPG is a primary brain tumour arising in the pons (middle) of the brain stem, is diffusely infiltrating and cannot be surgically removed.
Occurring mostly in children, the median survival rate in a cohort of 316 cases was 10.0 months and OS12 was 35% (Jansen et al, 2015.
Neuro‐Oncology 17(1):160‐166). Although radiotherapy prolongs survival, the majority of patients die within one year following
diagnosis. Systemic chemotherapy is ineffective, often due to an inability of agents to cross the blood‐brain barrier. Approximately 1,000
(data on file) individuals are diagnosed with DIPG worldwide each year.
Commenting Sabine Mueller MD PhD, Principal Investigator of the UCSF study, said: "The study has determined a proposed
dose range for MTX110 for Phase II and has shown that repeated delivery of MTX110 via CED is feasible and safe. In an
upcoming Phase II study efficacy in this patient population will be assessed."
Commenting further, Steve Damment, EVP R&D of Midatech, said: "DIPG is a devastating pediatric brain cancer with
limited treatment options and very poor outcomes. The overall survival data from this Phase I study are encouraging,
although further study of MTX110 in DIPG is required to establish whether it can make a difference to these patients and
Online Q&A Session
Stephen Stamp (CEO and CFO) and Steve Damment (EVP R&D) will be hosting an online Q&A session regarding this latest
development at 2.00 p.m. London time / 9.00 a.m. US East Coast time on Monday 19 October 2020. This session is open to
all existing and prospective shareholders. Those who wish to attend should register via:
https://us02web.zoom.us/webinar/register/WN_fwS5OEm8QiG5Uz7JvjWQ‐A where they will be provided with access
details. Participants will have the opportunity to ask questions during the session, but questions may also be submitted in
advance to : midatech@investor‐focus.co.uk
MTX110 is a water‐soluble form of panobinostat free base, achieved through complexation with hydroxypropyl‐β‐
cyclodextrin (HPBCD), that enables convection‐enhanced delivery (CED) at potentially chemotherapeutic doses directly to
the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non‐selective histone deacetylase inhibitor (pan‐
HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak®) is not suitable for treatment of
brain cancers owing to poor blood‐brain barrier penetration and inadequate brain drug concentrations. Based on
favourable translational science data, MTX110 is being evaluated clinically as a treatment for DIPG (NCT03566199,
NCT04264143) and recurrent medulloblastoma (NCT04315064), and preclinically for treatment of glioblastoma (SNO 2020
Abstract TMOD‐27). MTX110 is delivered directly into and around the patient's tumour via a catheter system (e.g. CED or
fourth ventricle infusions) to bypass the blood‐brain barrier. This technique exposes the tumour to very high drug
concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects.
Panobinostat has demonstrated high potency against DIPG tumour cells in in vitro and in vivo models, and in a key study it
was the most promising of 83 anticancer agents tested in 14 patient‐derived DIPG cell lines (Grasso et al, 2015. Nature
Medicine 21(6), 555‐559).
This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).