28 April 2023
Biodexa Pharmaceuticals PLC(Biodexa or the Company or, together with its subsidiaries, the Group)
Preliminary Results for the Year Ended 31 December 2022
Biodexa Pharmaceuticals PLC (Nasdaq: BDRX), a clinical-stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain, announces its audited preliminary results for the year ended 31 December 2022.
For more information, please contact:
Biodexa Pharmaceuticals PLC
Stephen Stamp, CEO, CFO
Tel: +44 (0)29 2048 0180
http://www.biodexapharma.com
Edison Group (US Investor Relations)
Alyssa Factor
Tel: +1 (860) 573 9637
Email: afactor@edisongroup.com
Biodexa Pharmaceuticals PLC (listed on NASDAQ: BDRX) is a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain. The Companys lead candidate, MTX110, is being studied in aggressive rare/orphan brain cancer indications including recurrent glioblastoma and diffuse midline glioma.
MTX110 is a liquid formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietaryformulation enables delivery of the product via convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour, by-passing the blood-brain barrier and avoiding systemic toxicity.
Biodexa's headquarters and R&D facility is in Cardiff, UK. For more information, please visit http://www.biodexapharma.com
Forward-Looking Statements
Certain statements in this announcement may constitute "forward-looking statements" within the meaning of legislation in the United Kingdom and/or United States Private Securities Litigation Reform Act. All statements contained in this announcement that do not relate to matters of historical fact should be considered forward-looking statements.
Reference should be made to those documents that Biodexa shall file from time to time or announcements that may be made by Biodexa in accordance with regulations promulgated by the US Securities and Exchange Commission, which contains and identifies other important factors that could cause actual results to differ materially from those contained in any projections or forward-looking statements. These forward-looking statements speak only as of the date of this announcement. All subsequent written and oral forward-looking statements by or concerning Biodexa are expressly qualified in their entirety by the cautionary statements above. Except as may be required under the relevant law in the United States, Biodexa does not undertake any obligation to publicly update or revise any forward-looking statements because of new information, future events or otherwise arising.
INTRODUCTION
Headquartered in Cardiff, UK, and quoted on NASDAQ in the US, Biodexa is a clinical-stage biotechnology company with three enabling drug delivery technologies. The Company de-listed from the AIM market as of 26 April 2023.
STRATEGY
Since the Strategic Review, and throughout 2022, we pursued a strategy of broadening our R&D pipeline by initiating internal programmes, collaborating with third party pharmaceutical companies on their proprietary active pharmaceutical ingredients, or APIs, and adding new indications to MTX110. New internal programmes were selected and prioritised based on the expected time to deliver proof-of-concept data for potential partnering.
Other than adding a second R&D collaboration with Janssen Pharmaceutica NV, for reasons not always within our control, we were not successful in finding partners for our internal Q-Sphera pipeline. As our cash runway ran down, and the market for biotech financing worsened in 2022, we considered the opportunities for refinancing the Company as a drug delivery company were limited. Accordingly, we concluded that repositioning the Company as a therapeutics company, focused on rare and orphan products in a merger with Bioasis Technologies, Inc. (Bioasis) with an attendant $10.0 million financing was the optimal solution for the Company. Although the merger and financing did not proceed, we were successful in raising $6.0 million, repositioning the Company as a clinical-stage therapeutics company supported by enabling technologies. In line with that repositioning, we undertook a restructuring in March 2023 including a cost reduction programme and termination of our internal Q-Sphera programmes. These initiatives are described more fully in the Chief Executives Review.
Following the repositioning of the Company, our priorities for 2023 reflect our modified strategy as follows:
Finalise recruitment of our second Phase I study in DIPG and report safety data.
Accelerate recruitment of our Phase I study in medulloblastoma.
We completed our assignment under our first R&D collaboration with Janssen, including optimising drug loading of Janssens proprietary large molecule using our Q-Sphera technology.
Explore opportunities for MTX110 in combination therapy for brain and metastatic CNS cancer.
Expand further our patent portfolio to cover new inventions and divisionals to strengthen existing patent families.
Seek a partner to develop, or co-develop, MTX110 once preliminary data from our Phase I study in recurrent GBM become available.
We added a new research programme coded MTD217 focused on developing new therapeutics options for metastatic cancers including leptomeningeal disease.
Initiate additional preclinical studies to assess the potential for MTD217 inhibitors in leptomeningeal disease.
During the year, we introduced a new COSHH assessment procedure to better quantify the safety of chemicals and third parties APIs being deployed in our laboratories.
Develop individualised learning programmes for staff members through participation in conferences, webinars and/or training programmes.
BUSINESS MODEL
Following our Strategic Review in March 2020, we reverted to a traditional biotech business model. We aimed to deploy our proprietary technologies to develop proof-of-concept formulations and then enter into licensing agreements with third party pharmaceutical companies.
In order to make the Company more investable and secure additional financing, the Board decided to reposition the Company as a therapeutics (as opposed to drug delivery) company in early 2023. As a result, the delivery of proof-of-concept clinical data is the primary focus of our business model going forward.
Development
Our intention is to build a balanced portfolio of clinical-stage development assets, ideally focused on oncology and on rare/orphan indications. Our only current clinical-stage asset, MTX110 is in Phase I development for three rare/orphan brain cancers.
Our R&D programmes may, like MTX110, be based on one or more of our enabling technologies.
Our aim is to enter into R&D collaborations with third parties to develop proof-of-concept formulations of their proprietary compounds using our proprietary drug delivery technologies. We will not be expanding our internal pipeline of drug delivery based programmes.
Manufacturing
To establish proof-of-concept in pre-clinical studies for potential licensees, we are able to manufacture non-GMP Q-Sphera products at pilot scale at our Cardiff facility. Upon securing a license partner who wishes to start clinical studies, our intention would be to technology transfer GMP manufacture of clinical trial supplies and ultimately full GMP commercial manufacture to a third party CMO. We would expect a licensee to assume the cost of manufacturing GMP product and commercial scale-up pursuant to a technology transfer agreement.
MTX110 is currently being manufactured to GMP standards at a CMO.
Commercialisation
Once proof-of-concept has been established, we intend to seek to license our products to a partner who would complete the clinical development and subsequently market and sell them in the licensed territory. In addition to reimbursement of development costs, the partner would be expected to make milestone payments based on sales targets and royalty payments.
Our development pipeline includes six projects of which one is partnered with Janssen:
CLINICAL-STAGE ASSETS
MTX110
Using our MidaSolve technology in combination with panobinostat, an otherwise insoluble drug, MTX110 is designed for direct-to-tumour treatment of intractable brain cancers. Panobinostat is currently marketed under the brand Farydak which is used orally in combination therapy for the treatment of multiple myeloma. We are currently researching the utility of MTX110 to proof-of-concept stage in three indications:
Glioblastoma Multiforme (GBM):GBM is the most common and aggressive form of brain cancer in adults, usually occurring in the white matter of the cerebrum. Treatments include radiation, surgical resection and chemotherapy, although in almost all cases tumours recur. There are approximately 2-3/100,000(1) population diagnoses of GBM per annum. Survival with standard of care treatment ranges from approximately 13 months in unmethylated MGMT patients to approximately 30 months in highly methylated MGMT patients(2).
Following IND approval in December 2021, we are in the process of recruiting patients in a Phase I study to assess the utility of MTX110 in recurrent GBM. The Phase I study is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. The study aims to recruit two cohorts, each with a minimum of four patients; the first cohort will receive MTX110 only and the second cohort will receive MTX110 in combination with lomustine.
Diffuse Intrinsic Pontine Glioma (DIPG):DIPG tumours are located in the pons (middle) of the brain stem and are diffusely infiltrating. Occurring mostly in children, approximately 1,000 patients(3) worldwide are diagnosed with DIPG per annum and median survival is approximately 10 months(4). There is no effective treatment since surgical resection is not possible. The standard of care is radiotherapy, which transiently improves symptoms and survival. Chemotherapy does not improve survival and one likely reason is that many anti-cancer drugs cannot cross the blood-brain barrier to access the tumour.
In October 2020, we reported the first-in-human study by the University of California, San Francisco (UCSF) of MTX110 in DIPG using a convection enhanced delivery (CED) system. The Phase I study established a recommended dose range for Phase II, a good safety and tolerability profile but also encouraging survival data in the seven patients treated.
Medulloblastoma:Medulloblastomas are malignant embryonal tumours that start in the cerebellum. They are invasive and, unlike most brain tumours, spread through thecerebrospinal fluid(CSF) and frequentlymetastasizeto different locations in the brain and spinal cord. Treatments include resection, radiation and chemotherapy. Approximately 350 patients(5) are diagnosed with medulloblastoma per annum and 3,800 people are living with the disease in the US. The cumulative survival rate is approximately 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively(6); however, recurrence is nearly always fatal with no established standard of care.
The University of Texas is undertaking a Phase I exploratory study in recurrent medulloblastoma patients using direct administration of MTX110 into the fourth ventricle, enabling it to circulate throughout the CSF.
(1)American Association of Neurosurgeons(2)Radke et al (2019). Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients. Acta Neuropathologica Communications 7:89 Online: https://doi.org/10.1186/s40478-019-0745-z(3)Louis DN, Ellison DW, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131:803820 (4)Jansen et al, 2015. Neuro-Oncology 17(1):160-166(5)Aboian et al (2018). Neuro-Oncology Practice, Volume 5, Issue 4, December 2018(6)Smoll NR (March 2012). "Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)".Cancer.118(5): 131322
TECHNOLOGIES
Q-Sphera
Our Q-Sphera technology employs 3-D printing techniques to encapsulate medicines in polymer-based bioresorbable microspheres. The microspheres may be injected to form depots in the body which release drug over predictable, sustained periods from one week up to several months. The features and benefits of Q-Sphera technology offer numerous potential advantages to patients and payors compared with immediate release products and other polymer-based technologies.
MidaSolve
Our MidaSolve technology increases the aqueous solubility of certain classes of anti-cancer drugs using complexes that solubilize these agents in water, thereby enabling them to be injected in liquid form directly into tumours.
The MidaSolve complexation agents (cyclodextrins) comprise a hydrophobic inner surface and a hydrophilic outer surface, and as a result are capable of forming host-guest complexes with normally water-insoluble molecules. The hydrophobic, poorly water-soluble drug associates with the inner, more hydrophobic surface of the MidaSolve host, while the hydrophilic outer surface allows the complex to dissolve at biological pH.
MidaCore
Our MidaCore technology platform is based on ultra-small gold nanoparticle (GNP) drug conjugates, which at 2-4nm are among the smallest particles in biomedical use. They are composed of a core of gold salts decorated with an array of therapeutic and/or targeting ligands. The small size and multi-functional arrangement around the gold core underpin the ability to improve biodistribution and target tumour and/or immune sites.
MidaCore design and synthesis GNP technology enables the production of nano-medications, which we believe are five-to-tenfold smaller than any other delivery vehicle in medical use.
CHIEF EXECUTIVES REVIEW
Introduction
With probably the most challenging market backdrop since the financial crisis in 2008/09 for financing biotech companies, 2022 was dominated by efforts to refinance the Company before its cash runway was due to expire in the first quarter of 2023. These efforts included our proposed acquisition of Bioasis and financing which was voted down by a group of shareholders followed by a successful, smaller financing and shift in strategic focus in early 2023.
Commercial Update
We made some incremental steps with our commercial strategy in 2022. In January we announced that Janssen had extended our R&D collaboration to optimise the drug loading and in vitro dissolution of a proprietary Janssen protein using our Q-Sphera technology. In March we announced that Janssen had further extended the collaboration to include the optimisation of drug loading and in vitro dissolution of a second protein. We have met our objectives with the first assignment and continue to work on the second.
R&D Update
MTX110
Employing our MidaSolve technology, MTX110 solubilises panobinostat, a histone deacetylase (HDAC) inhibitor currently used in the treatment of multiple myeloma. In a liquid formulation as MTX110, panobinostat can be delivered directly to a patient's tumour under constant pressure via a catheter system (Convection Enhanced Delivery, or "CED"), thereby bypassing the blood-brain barrier and allowing for high drug concentrations and broader drug distribution in and around the tumour while simultaneously minimising systemic toxicity and other side effects.
During 2021, following receipt of promising pre-clinical data from tumour models and in vitro patient-derived cell lines, we reprioritised our development of MTX110 in favour of GBM, potentially a very significant opportunity with annual diagnoses of 2-3/100,000 population and global market potential of US$3-5 billion. In December 2021 we received an IND to proceed with an open label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by CED via implanted refillable pump and catheter. The study aims to recruit two cohorts, each with a minimum of four patients; the first cohort will receive MTX110 only and the second cohort will receive MTX110 in combination with lomustine. We announced our first patient enrolled in the trial in November 2022 and the Data Safety Monitoring Board recommended the dose be escalated to 90M, the expected optimal dose for patients. We are aiming for preliminary safety and efficacy data (in the form of Progression Free Survival data) for the first cohort in the third quarter of 2023.
We initially began developing MTX110 for DIPG, the ultra-rare, highly aggressive and inoperable form of childhood brain cancer. We have an ongoing Phase I study in the US with one more patient required for completion. We are also evaluating the utility of MTX110 in medulloblastoma in a pilot study at the University of Texas.
Q-Sphera
Development programmes in our internal Q-Sphera pipeline are designed to address large markets but also offer significant clinical benefits compared with current therapies and, importantly for reimbursement, savings to the healthcare system.
MTD211 (Q-brexpiprazole)
We have developed a long-acting formulation of brexpiprazole. In in vivo studies, MTD211 demonstrated that a single dose is expected to deliver therapeutic blood levels of brexpiprazole over a period of approximately three months. Marketed under the brand name Rexulti, brexpiprazole is indicated for the treatment of schizophrenia and adjunctive treatment of major depressive disorder (MDD) and is currently only available as an immediate release oral tablet. The market for anti-psychotic drugs has shifted towards long-acting formulations for reasons of improved patient compliance and lowering of payor costs associated with patient hospitalisation events. MTD211 is available for licensing.
MTX223 Q-Protein, partnered with JanssenWe are continuing to collaborate with Janssen on a second large molecule to optimize drug loading and in vitro dissolution profiles.
MidaSolveMTD217 (MTX110 plus an oxphosphorylation inhibitor)
Our recently initiated MTD217 programme explores simultaneous inhibition of aerobic glycolysis and oxphosphorylation, key metabolic pathways for cancer cells. Our programme is centred around a number of new water-soluble drug formulations that can be easily infused or injected simultaneously, or sequentially, directly into the cancer microenvironment, disrupting metabolic functions in a highly localised manner and limiting off-target toxicity. We have already demonstrated up to a six-fold synergistic effect of administering MTX110, with an oxphosphorylation inhibitor in vitro in three patient-derived cell lines. On the back of those data, we have established new patent positions to protect these combination formulations.
Our initial target is treatment of leptomeningeal disease, a lethal complication in which metastatic cancer cells invade the cerebrospinal fluid and central nervous system. In collaboration with several large academic centres, we are now accelerating preclinical studies to generate proof of concept data that can support a future clinical trial application.
MidaCore
We are using our GNP technology to engineer a formulation of methotrexate for the topical treatment of psoriasis. Pre-clinical data have shown that MTX114 normalises skin thickness in mouse psoriatic skin models. There are estimated to be over 100 million(2) people who suffer from psoriasis worldwide. MTX114 is available for licensing.
(1)Jansen et al, 2015. Neuro-Oncology 17(1):160-166(2)Psoriasis.org
Strategic Repositioning in 2023
Since our 9.0 million (net) fundraise in July 2021 we had consistently forecast that our cash resources would fund operations into the first quarter of 2023. As our cash runway ran down, and the market for biotech financing worsened in 2022, we found the opportunities for refinancing as a drug delivery company were, for practical purposes, non-existent.
Bioasis
In response to the lack of appetite to refinance a drug delivery platform company, the Board looked for opportunities to merge or acquire other companies to create a more investable therapeutics company. Accordingly, the Board proposed an acquisition of Bioasis, a multi-asset company listed on the TSX-V exchange with two platform technologies that had been validated by partnerships and licenses with pharmaceutical companies with potential milestone payments totalling in excess of US$200 million. The enlarged, merged company would have been repositioned as a therapeutics company with an internal pipeline focused on rare and orphan products. Importantly, we had secured a $10.0 million financing conditional upon the acquisition. One shareholder corralled sufficient votes to ensure the requisite Special Resolutions to approve the acquisition and financing were not approved and, accordingly, the acquisition and financing did not proceed.
Financing
After the General Meeting on 23 January 2023 at which the Bioasis acquisition and financing were voted down, we had only a short time to secure funding, failing which the Directors would have no option other than to place the Group in Administration. At this time, the Company engaged Quantuma Advisory Limited, a specialist business advisory firm, to advise the Board on its obligations to creditors, in particular. Ultimately, we were successful in raising $6.0 million using a cashbox structure which did not require shareholder approval but on terms materially more dilutive than those of the conditional financing originally proposal alongside the Bioasis acquisition. At the time, in early February, the Board had considered it had no actionable alternatives to Administration other than the $6.0 million financing. The financing is expected to allow the Group to fund operations into the fourth quarter of 2023 and progress its clinical-stage asset MTX110, in particular.
Repositioning the Company as a Therapeutics Company
In the course of raising additional finance for the Company in late 2022 and early 2023, it became clear that a therapeutics company was more investable than a drug delivery platform company. Accordingly, the Board determined that the Company should be repositioned as a therapeutics company supported by three enabling technologies. Going forward, our priority will be moving our development programmes into the clinic and generating clinical data to demonstrate proof-of-concept. We intend to continue our existing, and seek new, R&D collaborations for our drug delivery technologies but we will not be expanding our internal drug delivery platform.
De-listing from AIM
The Board decided to cancel the Companys AIM listing for a number of reasons including: an increasingly smaller proportion of trading in the Ordinary Shares is conducted on AIM compared to NASDAQ; improved liquidity through concentration of trading in the Companys securities on a single market; and the cost, management time commitment and the burden of complying with the AIM Rules and maintaining a quotation on AIM is duplicative of that for complying with the NASDAQ rules. In addition, the Company intends to seek opportunities to expand its pipeline through the acquisition and/or in-licensing of additional development programmes. Given the Companys market capitalisation, transactions are likely to be deemed reverse takeovers under AIM rules, requiring suspension and relisting via a new Admission Document which is both time-consuming and costly.
Change of Name
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Preliminary Results for the Year Ended 31 December 2022 - GlobeNewswire
