PYX Resources: Achieving volume and diversification milestones. Watch the video here.
The inclusion of ‘tech transfer’ in the recent job description is significant. It suggests that the proof-of-concept stage is nearing completion and they are preparing to manufacture a Q-Sphera drug for clinical trials. The closure of Bilbao will require Midatech to outsource the manufacturing to a CMO.
That will involve tech transfer, and Stamp alluded to that in September’s webinar:
“So, the listeners will understand that Q-Sphera is a unique manufacturing process, which is what makes it so valuable and so differentiated from the traditional methods of PLGA manufacturing. So, you can't go along to a CMO and say, print these tablets or make these tablets for me, all the technology, the know-how is inside Midatech.
So we’re in the process of lining-up some partnership agreements with, well, that'd be one in the end, but we’re talking to several CMOs, whereby we can take the smallest scale equipment that we salvage from Bilbao, we need to add one or two pieces to it and install that inside a CMO which will have GMP capability such that we can manufacture at least clinical trial scale and then it will be the partner that will take on the scale up to commercial manufacturing.”
I don’t know about an interesting afternoon, NicetoMichu, but it could be an interesting year. If they are all new positions at Cardiff – then they are getting ready for something. They let 5 staff go last year as part of the strategic review – now they are recruiting. That's progress.
From the job description: “The position will guide and support clinical manufacturing requirements, providing Quality and Compliance input across manufacturing process development, analytical development and tech transfer activities.”
Could the next news be that some of the Q-Sphera formulations have reached proof of concept and partners are ready to take them forward?
Midatech are recruiting:
https://www.midatechpharma.com/about/careers
There is a big emphasis on Q-Sphera in the job summaries, plus manufacturing in the Quality and Compliance Lead. CMC is an integral part of IND and NDA.
Looks promising.
Midatech are trying to make a long-acting MAB depot. It would be the first ever. It is difficult to achieve using the standard emulsion encapsulation process because the high temperatures denature the protein.
The Q-Sphera platform doesn’t use high temperatures and therefore it may be possible to print the MAB micro-spheres without changing the structure of the MAB.
They already have two partners for four Q-Sphera formulations:
https://www.midatechpharma.com/pipeline
If Midatech can get them to proof of concept stage, then a license agreement should follow. The partner will be responsible for all clinical development.
Cash should be around £8 million. The burn rate is about £400K per month.
Nast, it was originally called MTX102 – a Type 1 Diabetes Vaccine. In July 2019 they reported that it had been well tolerated in the first in human study and no serious adverse events were reported.
The follow up phase was due to complete in May 2020 – so an update on the findings was expected by the start of the summer – but there wasn’t one. It no longer appears in the updated pipeline – with its new focus on Q-Sphera.
Merry Christmas everyone. Let’s hope 2021 is Midatech’s year to shine!
Michael Hennigan (Marathon Petroleum CEO?) could be back. He bought a large number of shares (1.8 million) through SpreadEx for around 25p in May and June and sold them all again for between 40p and 80p in July.
https://www.lse.co.uk/rns/MTPH/form-83-midatech-pharma-plc-wmffbhev3wb4vtc.html
CMS and A&B each subscribed for just over 100 million shares in January 2019. This became around 5 million each after the 1 for 20 consolidation in March 2020. The subscription came with warrants at 50p (now £10). I have some and, like Borsaci06 has said, so have many other posters. They are pretty much worthless.
CMS and A&B own around 16% of the company. If they were going to buy the company, I think they would have done so by now. It was up for sale for a short period of time when it looked like liquidity had completely dried up when the pandemic struck. That would have been their moment to buy.
This third strategy, with its emphasis on the Q-Sphera formulations and partnerships, may well work. Stamp sees lots of “reasons to view the future with excitement and confidence”. He also said, “our target is to land our first licence fee (multimillion dollar) in the first quarter of next year”. Not long to go – we’ll soon find out.
20p – I can’t see it dropping to that level. It’s way undervalued as it is. It’s just released clinical data showing MTX110 could double DIPG survival beyond a year. That was on 19 October and the SP was at 30p before then.
Emergex raised another $11 million last week – that’s $22 million raised in total this year.
https://emergexvaccines.com/emergex-vaccines-raises-us11-million-to-advance-pipeline-of-synthetic-t-cell-vaccines-for-infectious-diseases/
I view an investment in Emergex as an indirect investment in MIdaCore. If the vaccines are successful, Midatech will receive milestone and royalty payments.
They might be a little late for the present pandemic – but the threat of future pandemics will mean governments will need to be prepared. Sally Davies, former chief medical officer for England, said recently:
‘Will we simply respond to the here and now, or do we take a moment to stop, look up and see beyond the horizon of this pandemic towards the next one?
Recognising this, we can, and must, say “never again”. We must do better to identify the next health threat, respond to that threat before it becomes an epidemic or pandemic, and if it does, recover in a way that does not exacerbate health, economic and social inequalities.’
With its universal T-cell vaccines, Emergex could play a vital role in the preparation for and prevention of future pandemics. They can be rapidly produced and cost-effectively scaled. And it’s good news for those scared of needles because delivery is by a microneedle skin patch:
https://www.researchgate.net/figure/Microneedle-patch-for-influenza-vaccination-A-The-microneedle-patch-contains-an-array_fig1_317979186
Sentiment. The one thing that needs to change, that’s for sure. Midatech is risky – but probably nowhere near as risky as it once was.
Investors need to acknowledge that the company has changed substantially since the start of 2018. Back then they had 4 premises – 2 in the UK, 1 in Spain and 1 in the US, with over 80 employees, a huge cash burn and little money coming in. The strategy of going for inorganic growth in the US to help fund research in the UK didn’t work – the American dream became a bit of nightmare.
The purchase of the US business in late 2015 caused the first major crash in the SP, and then, when they sold it again at the end of 2018, L&G had had enough and sold out, resulting in another spectacular decline. The US activities consumed time, money and resources, and I think it delayed the company from getting on with advancing its tech-based drugs. They only got those into the clinic in the middle of 2018 – 3.5 years after IPO. That’s too long. If they had got on with them from the start, for example, MTD201 was already on the shelf in Cardiff ready to be investigated, the news would have been wholly good, and the sentiment would have been positive.
Over the last 2 years, the platforms and the drugs have performed very well, the number of Q-Sphera formulations has increased to 7 (3 partnered), they have 1 premises, 20 employees and cash burn of about £5 million per year, with a 12-month cash runway.
It's disappointing, especially since Monday’s news was positive. The UK Investor Magazine had the headline:
“Midatech Pharma MTX110 could double rare brain tumour survival beyond a year.”
For DIPG - that’s real progress.
At IPO the M cap was £74 million, and at that stage all 3 platforms were unproven technologies, and no drugs had reached clinical stage. Since then, all 3 platforms have been shown to work, producing safe and effective drugs in humans. Q-Sphera is showing huge potential. And yet, the M cap remains at £20 million and does not reflect the substantial progress that has been made.
I came across a post on the DIPG TAC Facebook page from August 2019. They appear to have had personal experience of DIPG and comment on possible treatments, including CED of MTX1110. They explain why they favour the multi-catheter delivery system. I’ve not included the whole post.
“Too many drugs either don't translate into humans, having worked to a degree in murine modelling, or don't bypass the blood brain barrier or both.
It's of critical importance to this author that you get the optimal dose concentration to the tumour site. The same drug in different concentrations has different effects. How to do this?
CED or Convection Enhanced Delivery.
We believe, (but don't know) that the single catheter method in the USA manufactured by Brainlab is not optimal. Why not? Because you don't get a fast enough flow rate through the single catheter to get sufficient volume simultaneously to the tumour site to provide whole tumour coverage. It's not a bad delivery system, just inefficient and thus sub-optimal. But what is bad is that the child needs a catheter inserted and extracted in each infusion cycle, which is highly onerous, almost akin to a biopsy every cycle.
The optimal device involves a one time surgery implanting 4 connected catheters directing optimised concentration and dose of drug to the tumour site in the pons, and each cycle of treatment infusing drug is a relatively simple and non- invasive procedure.
In a simple analogy, we call this a "drug highway" to the tumour site. But what use is a super highway unless top class cars (drugs) travel along it?
…Panobinostat or MTX-110, which is the CED usable version. This author remains highly sceptical of any benefit from this drug given orally, even under the new protocols being advocated in California; it has little evidence of being able to bypass the blood brain barrier, and causes systemic toxicity. Yet it has a wholly different effect when introduced via CED. We remember well what the early CED expert stated when he tried it in his lab: "incredible". This report corroborated the widely respected Grasso report on the comparisons of HDAC inhibitors, which pronounced Panobinostat as the top (by some distance) HDAC drug against DIPG.
This author knows of a patient who tried MTX-110 in optimized doses, with 4 weekly cycles of infusion. The child walked into hospital in the morning, and walked out in the evening post infusion. The medics, viewing the child's MRI's, said they had never seen such a positive result. Yet it hasn't been used again in any child in a continuous cycle of multiple infusions in the same doses ever since. But that's another story for a published book one day.”
These are encouraging results because, apart from radiotherapy, there are no treatments for DIPG. It has been like this for the past 40 to 50 years. No progress.
The median survival time following radiotherapy is ~ 10 months. Only 10% of children survive for 2 years following their diagnosis.
This study shows that MTX110 is safe – even after a doubling to trebling of the initial concentration. The median survival time was ~ 26months, although this will need to be confirmed in the follow up study.
There are two aspects to the treatment, the drug and the CED catheter system. At UCSF they have been using a single catheter which will have been surgically implanted every time there was a new infusion. These children are already poorly – so I don’t think repeated surgery is helpful.
In the follow up study, the 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. One of these systems is Renishaw’s Neuroinfuse, which has been used successfully at Southmead Hospital, Bristol:
https://www.youtube.com/watch?v=0m2Vgn9EvYM
Apologies if someone has already pointed this out. The source of Traumakine in the Phase I/II clinical trial was Rebif, formulated for intravenous use. See under ‘Study design’:
https://www.researchgate.net/publication/260119599_The_effect_of_intravenous_interferon-beta-1a_FP-1201_on_lung_CD73_expression_and_on_acute_respiratory_distress_syndrome_mortality_An_open-label_study
The 28-day mortality rate in the Traumakine treated patients was 8%, much lower than the 32% in the control group.
The authors commented:
“We showed that 10 µg per day of intravenous FP-1201 could be given without adverse effects, and with a clear biological effect: IFN-beta activity, as marked by MxA concentrations, rose to levels several times higher than those resulting from subcutaneous or intramuscular interferon administration.”
This is the first time since IPO that the tech and drugs have had centre stage. They are either going to perform brilliantly or strut and fret their hour upon the stage and then be heard no more (credit to Macbeth).
(1) Q-Sphera – MTD211, MTD214, MTD215, MTX212, MTX213, MTX214, MTD201
Seven formulations. Three of them are partnered. Stamp said the target is to land first multimillion dollar licence fee for one of these in the first quarter of next year.
(2) MidaSolve – MTX110
The final patient for the UCSF study had been recruited by the middle of June. The infusions of MTX110 are repeated every 4 to 8 weeks. They only need to determine the maximum tolerated dose – so let’s say they need 3 to 4 infusions to evaluate any adverse events.
The principal investigator on the study, Dr Sabine Mueller, has described the safety profile as “excellent”. It was originally designed with five dose levels; however, since MTX110 was well tolerated, a further two higher dose levels were added.
News is imminent.
(3) MidaCore – MTX114
Not sure about MTX114.
Stamp thinks that Emergex are the best people to take the MidaCore platform forward. License agreement is in place. However, they need to sort out manufacturing facilities following the closure of Bilbao.
Emergex are making progress with their second generation COVID-19 vaccine. They are also working on T-cell vaccines for Dengue Fever, Zika, Ebola and pandemic Flu. They are well-funded, and Finian Tan thinks Emergex will make a big impact.
The time taken to sign the collaborations was impressive. Stamp said, “we signed two collaborations in that period in only 3.5 months and I have to tell you I was astounded and pleased by that. That is lightning speed for a biotech company.”
Good summary starting at 16:05
https://kr-asia.com/long-term-value-comes-from-profitability-says-vickers-venture-partners-dr-finian-tan
I have never been that impressed with Midatech’s IR. Developments at Emergex have consequences for the MIdaCore platform and thus Midatech. Even if a development was considered to be non-regulatory news, could they not at least look to see if it complied with the REACH guidelines?
What Emergex are attempting to do is fascinating. Instead of producing a conventional vaccine that tries to stop the virus from entering the cell, they are trying to make one that recognises and kills infected cells. Emergex have said that with a traditional vaccine there is a risk of antibody dependent enhancement (ADE).
There was an article about ADE on The Guardian website on Sunday. British scientists have launched a major study aimed at uncovering the critical role that human antibodies and other immune defences play in the severity of Covid-19 cases. In the article, Professor Michael Levin (Imperial College) said:
“This study could go in two very different directions. It could reveal that cross-reacting antibodies explain why children are less likely to suffer from severe Covid-19, or it might show patients’ own immune responses cause life-threatening effects.”
“After the pandemic began we started seeing severely ill, infected children with intense inflammation and multi-organ failure. We were puzzled because their illness was occurring not at the height of their infection but several weeks afterwards – when the virus had gone but antibodies were high. We feared those antibodies might actually be causing the damage.”
“The Dengue fever virus provides a good example. There are three strains of it. If you get infected with one strain that might not make you terribly ill. But if you later get infected with a second, different strain, you could be in trouble. The antibodies your immune system first made can actually make the disease worse when you encounter a slightly different strain of the virus.”
This drawback has plagued attempts to develop a vaccine for dengue fever. Triggering antibody production – as vaccines attempt to do – can enhance the disease’s impact, unless those antibodies are effective against all three dengue strains.
Emergex’s universal T-cell vaccines are designed to effective against all strains found within a virus family. They enlarge the body’s natural immune response by programming T-cells to quickly recognise and respond to viruses. This approach is aimed at providing effective prevention of disease while eliminating the allergic, autoimmune or antibody mediated side effects associated with conventional vaccines.