The LABINA trial for wet Age-Related Macular Degeneration

The LABINA trial for wet Age-Related Macular Degeneration updated their business hours.

As we approach the end of 2019 it’s time for a quick update. Over the last few months the focus has been on MagaFab and, as we hinted at in the last post, getting some critical safety data on this molecule. The very good news is that a few weeks ago we undertook these studies and MagaFab passed with flying colours. This of course is also great news for our spinout company PanAngium, and provides the ammunition we need to get funding into the company to now scale up MagaFab manufacture and take the work towards clinical trials.

We therefore end the year on a positive note, knowing that the prospect of getting our novel therapy into patients is a step closer. As soon as we have more news you’ll be able to read about it here, but for now have a peaceful and enjoyable Christmas.

An update here is long overdue, but there are good reasons for the silence of the past few months. Preparation for clinical trials always involves rigorous safety testing, and by the middle of last year our antibody Magacizumab was well on track to meet the demands of the regulatory authorities (FDA in the US, MHRA in the UK). Without their approval it is simply not possible to start injecting drugs into patients, and to our frustration Magacizumab was found wanting in one key area.

But this is not the end of the story. Antibodies are big molecules, and its possible to break them down and just use one bit. Any patients with wet AMD who have heard of Avastin and Lucentis, may know that Lucentis is a fragment of Avastin. So to cut a long story short, we've been working on ways to generate our own Magacizumab fragment and have succeeded - we call it MagaFab - and over the last few months have obtained funding to develop MagaFab and repeat the safety testing.

The net result is a delay to getting this to the clinic, but we're back on track and moving forward. And as a footnote, Magacizumab may still have an exciting future in diseases away from the eye. More on this next time!

These last few months have presented us with an unexpected challenge, and the pause since our last post reflects the thinking and new planning we've had to come up with to keep things moving forward. To cut a long story short, we've discovered that Magacizumab (our therapeutic antibody) may need to undergo some modifications before it can be used in patients.

In the ten years or so that we've been working on this project this is the first time we've really had to divert from the planned route, but perhaps it's inevitable that in the long and complex process of going from a lab discovery to treating people with AMD, we were bound to hit a bump in the road at some point.

So, whilst the LABINA trial remains in our sights, we've been working to generate extra funding to support some additional development work, and also accept that this will delay the commencement of clinical trials. Meanwhile, we continue to study our protein of interest (LRG1) in the lab, and our wonderful hard-working research team keep generating results that convince us we're on the right track.

Eight days after returning from Chicago and we're off again. And this time it's to the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO). Like most big scientific societies, ARVO hold their annual conference in cities across the US, and notably next year for the first time, outside the US - although only just, when they go to Vancouver. But this year the meeting is in Hawaii. We almost didn't go, because of the sheer distance involved, but with the project at such an exciting stage and various collaborators and companies to talk to, it was clear we needed to attend.

The big news in our project is that the company making Magacizumab, our therapeutic antibody, have succeeded in generating large quantities of extraordinarily pure material at high concentration. Both of these points are important, the former because the eye is incredibly sensitive to certain impurities called endotoxins, and the second because a high concentration means not having to inject people so frequently. We'll be updating scientific colleagues at ARVO on our progress, while also learning about what other groups are up to, and all the latest news on emerging therapies for AMD. If you're interested in knowing more about the conference then follow the ARVO page at https://www.facebook.com/ARVOinfo/

ARVO ARVO is the largest and most respected eye and vision research organization in the world, serving an

So here we are in Chicago sharing some of our work with around 20,000 cancer scientists and clinicians. Attending conferences like this is an essential and mostly enjoyable part of the job, but there are times, like this morning when it's -2oC here and snowing, that I look at the decidedly warmer conditions back home and wonder what on earth possessed me to come.🤔

In a few weeks we're off to another conference, this time in Chicago, and it's all to do with cancer. Many of you will know that the monthly injections you receive, be it Eylea, Lucentis, Avastin etc., work by stopping the blood vessels leaking in the retina, hence the swelling subsides and vision improves. What's interesting from a historical perspective, is that these drugs have their origins in cancer. And the key biological link between wet AMD and many different types of solid cancer, is abnormal blood vessel growth. Avastin was initially developed for colorectal cancer (where it is still widely used), until some years ago a bright spark working in a lab somewhere had the idea that perhaps Avastin might also be effective in wet AMD. The rest, as they say, is history.

In our project, we've done the reverse. We started by developing our antibody, Magacizumab, to treat diseases of retina and in particular wet AMD (this work is funded by the Medical Research Council), but a few years ago we began to wonder whether the antibody might work in other conditions that feature abnormal blood vessels. So we began investigating cancer. For now, all we can say is that we have some interesting data that we're planning to publish this year, and that if we're ever going to start testing Magacizumab in cancer, it's become important for us to learn more about this vast and complex family of diseases.

Another update! Everything is on course as the company we have contracted to provide the drug has now completed the manufacture process and generated the first batch of Magacizumab. In January 2018 this will go to another specialist company to check its safety. When this is complete later next year we will begin the lengthy regulatory process and manufacture the clinical grade batch of Magacizumab in readiness for our clinical trial in 2019. Its a slow process but we are making progress and getting ever closer to the clinical trial. Further updates will come during 2018. Have a wonderful New Year from all of us involved in this project.

Our pre-clinical work continues apace. Hopefully entering clinical trial by early 2019. Its a long old process!

I get nudged by Facebook if I haven't posted in a while, and an update is certainly overdue! The good news is that the production of Magacizumab, our novel therapeutic antibody, is continuing according to plan. The company undertaking this work have now established the optimal growth conditions for the cells that produce Magacizumab and also the best strategy for its subsequent purification. We also now have data on a suitable formulation for injection into the eye, and excellent initial results on the stability of the antibody. And during the summer we obtained a substantial new research grant (~£1.7M) from the Wellcome Trust to conduct more basic research into our drug target, LRG1 so that we can better understand how and why it disrupts blood vessels. The next big milestone for us will be the generation of a batch of Magacizumab (probably end of next month) that will be used for pre-clinical safety testing. That work will take us well into 2018, and if we emerge from those studies with a satisfactory safety profile then it's more or less a clear road ahead to testing in patients with AMD.

We have just returned from Baltimore and the latest annual meeting of the Association for Research in Vision and Ophthalmology (ARVO). Attending the ARVO meetings is an essential part of our work as this is where we maintain contact with collaborators, meet and network with companies who may eventually develop our therapeutic antibody, and look out for scientists who might come and work with us in the future. This latter point was especially relevant this year as John Greenwood and I were recently awarded a prestigious Wellcome Trust Investigator Award to continue our basic science studies into LRG1 - the protein we discovered that led to, among other things, this page! Meanwhile, the preparation of our clinical grade antibody is moving along nicely, and we are due to start the safety and toxicology testing later this year. Everything remains on track for us to be treating the first patients late in 2018, by which time we may well have attended the next ARVO. The last slightly bizarre picture gives a clue as to where the next meeting will be held!

An interesting article in Nature this week about getting a drug to market, and the need to show that it really does work. https://t.co/QGM9SBA0KK

pbs.twimg.com

After some lengthy contract negotiations - not helped by the falling value of the GB£ post-Brexit - the good news is that we have now started the manufacture of the clinical grade antibody (Magacizumab). The process will take several months, largely because the end product has to be of extraordinarily high quality in order to avoid possible adverse reactions to trace contaminants when injected into patients. Despite the delay in getting the manufacturing under way, we expect to make up time during this next part of the work, and we're still on course to start the Phase I clinical trial next year. Next up is a meeting in February with the UK regulatory body, the MHRA, who will advise us on what safety testing we must undertake before we go into patients.

A few more months have rolled by since our last post, and the pre-clinical work continues. The good news is that work to develop a cell line is now complete, which means we can now generate our therapeutic antibody (Magacizumab) in the kind of quantities we're going to need to conduct the trials. The next step is to transfer the cell line (from the company that made it) to another company who will scale everything up and generate the antibody at a level of purity suitable for injection into patients. The regulatory authorities keep a very close watch on these matters, and all new compounds need formal approval before they can go to the clinic.

Meanwhile we have just returned from a conference in Boston where the focus was vascular biology, and where we learned much about therapeutics being developed and tested in this area, and also about other diseases in which we might eventually test our antibody. These include various cancers, and also diabetic retinopathy. To pursue these additional disease studies will require significant extra funding, so some of our energies are now focused on trying to raise money with this in mind.

This weekend we returned from ARVO2016, the annual eye conference in the USA which this year was in Seattle. As always the schedule was packed, with much interesting new science and important opportunities for networking. We weren't presenting anything on the LABINA clinical trial as we're still some way from starting to treat patients, but it was useful to learn about attempts elsewhere around the world to design and deliver new therapies for AMD, ranging from eye drops and conventional drug treatments to stem cell transplantation.

Back home the development of the master cell line has hit a minor delay and may now take two or three additional weeks to complete. We have also been looking at possible companies that we might use, following completion of the cell line work, to generate the large quantities of clinical grade antibody we'll require for clinical testing.

Had our monthly group meeting yesterday and all is progressing well. The Company making the cell line that produces our antibody (Magacizumab) are hitting their milestones and stay on course to complete their work in July. With Easter coming up, John Greenwood and I are off to Singapore where we'll be giving talks and meeting other scientists at the Eye Research Institute. Then some holiday time in Indonesia. Can't wait.

Professor John Greenwood (left) and Professor Steve Moss (right) of University College London Institute of Ophthalmology. Joint Principle Investigators of the LABINA clinical trial for wet AMD

First official meeting of the LABINA trial project today with representatives from the Medical Research Council (funding the project), UCL Clinical Trials Unit, UCL Translational Research Office and UCL Business. We have a great team and its all systems go.

It's been a while since I last posted, not because of a lack of activity, rather that the activity is not particularly exciting. I mentioned last time that the tendering process was under way, and the good news is that we seem to have crossed all the 'Ts' and dotted all the 'Is', and that tender can now be published. If you happen to fancy your chances at making clinical grade antibody then feel free to bid - such is the nature of public tendering.

The other thing that's going on is that the company who are working on the cell line (that will produce the antibody) are reporting excellent progress in line with projections. Why is this 'excellent' and not merely 'routine'? The answer is that in this kind of work it is common to hit snags and glitches, so simply sticking to the anticipated time lines does indeed qualify as excellent.

Finally, our funding formally kicked in on Feb 1st, a moment of reflective celebration for all the team, and we'll be holding an official project launch meeting with the MRC next Monday. For readers with wet AMD we are approximately two years from being ready to inject the antibody for the first time.

With the preparation of the cell line under way, we now have to start getting ready for the next phase, which is to bulk up that cell line in order to prepare several kilograms of clinical grade Magacizumab. This work will be done by another specialist company, and because the contract is high value, we have to go through a process of 'public tendering'. This is where we set out what we need, and invite companies to bid for the contract. It's all very tedious but it's a legal requirement and it can take a while to set up, which is why we're beginning the process now, several months in advance.

This has been an important week for the LABINA trial as we saw the beginning of the very first steps on the way to manufacturing Magacizumab - the antibody that we will test in patients with AMD. An antibody has to be made by cells growing in the lab, and the aim at the beginning is to isolate cells that make the antibody in large quantities. This is specialist work so we're paying a company to do this for us - hopefully the cell line will be ready early next year.

Stories in science often have unusual beginnings. The AMD clinical trial that John Greenwood and I are kicking off, might never have happened if it hadn't been for a beer with Mark Cedric Gillies at the Sheraton Yankee Trader in Fort Lauderdale many years ago. Must also acknowledge key early studies from Jenny McKenzie who did the analysis that led to our discovery of LRG1, Xiaomeng Wang who figured out how this protein works, Sabu Abraham who did much of the work that proved LRG1 to be a promising therapeutic target, and Vineeta Tripathi who analysed more than 100 monoclonal antibodies against LRG1 to eventually find the one that we turned into Magacizumab. Much more to tell, and many others who have played and continue to play important roles.

The Medical Research Council have announced details of our clinical trial on their web site. Read about it here..http://www.mrc.ac.uk/news/browse/new-target-for-macular-degeneration-gets-funding-for-clinical-trials/

New target for macular degeneration gets funding for clinical trials - News - Medical Research... The MRC is to fund researchers at the UCL Institute of Ophthalmology and Moorfields Eye Hospital to conduct clinical trials into the use of a humanised monoclonal antibody to treat patients with age-related macular degeneration (AMD).

The Medical Research Council today announced the funding of our clinical trial.

We're looking forward to seeing UCL and the Medical Research Council issue a joint press release about our work within the next few days. Stay tuned.

On my way to Larnaca this morning for a short meeting of the Cyprus Ophthalmological Society - always the chance of picking up some new insight into the latest AMD trials and emerging therapies.