Francis Crick Institute Scientists Granted License to Edit Genes in Human Embryos – What will the Initial Impacts be?

In a global first, the UK’s Human Fertility and Embryology Authority (HFEA) have granted permission to a group of London-based scientist to edit the genomes of human embryos for research. Announced on 1st February 2016, the endorsement is the first of its kind by any national regulatory authority.

The approved research application from the Francis Crick Institute led by Dr Kathy Niakan is aimed at identifying and understanding the gene human embryos need to develop successfully. The research team will look at the first seven days of a fertilised egg’s development in the hope of providing important knowledge for understanding how a healthy human embryo develops.

Dr Niakan will be using CRISPR-Cas9 technology which enables the scientists to modify, identify, or replace genetic defects.

Commenting on the news, Paul Nurse, Director of the Crick, explained: “I am delighted that the HFEA has approved Dr Niakan’s application. Dr Niakan’s proposed research is important for understanding how a healthy human embryo develops and will enhance our understanding of IVF success rates, by looking at the very earliest stage of human development.”

So what will be the initial impact of this authorisation?

Controversy

With a topic such as genetically modified human genomes, controversy will not be far behind, with those opposed to the authorisation believing that this will open the door to ‘GM babies’.  It must though be made clear that this authorisation specifically states that it will be illegal for the scientists to implant the modified embryos into women.

Speaking on the ethical implications of the decision, Dr Sarah Chan from the University of Edinburgh said:

“The use of genome editing technologies in embryo research touches on some sensitive issues, therefore it is appropriate that this research and its ethical implications have been carefully considered by the HFEA before being given approval to proceed.”

“We should feel confident that our regulatory system in this area is functioning well to keep science aligned with social interests.”

IVF

Moving away from the controversy, it is good news for those receiving IVF treatment. With the increased knowledge that will be gained from the research, IVF success rates should dramatically improve thanks to the focus on miscarriage and fertility. Speaking to the BBC, Dr Kathy Niakan has said that the reason why she applied for the approval to edit human embryos was that “we would really like to understand the gene needed for a human embryo to develop successfully into a healthy baby”.

Dr Niakan went further to explain that “the reason why it is so important is because miscarriages and infertility are extremely common, but they’re not very well understood”.

Ethical Approval

The research is still in need of ethical approval before the programme can begin, but it is looking likely that this will be granted and the research will begin in the next few months.

With the research likely to add to the basic scientific knowledge needed for assisting infertile couples becoming parents, and to reduce the heartbreak of miscarriage, this is but one practical positive that will hopefully come from the work of Dr Niakan and her team.

Not only does the research have the potential to greatly assist in IVF treatment, it is another display of the excellent position the UK holds in the genome editing field of research and the advances being made by UK scientists.

At Cell Therapy Manufacturing & Gene Therapy Congress on 2nd – 5th February in Brussels, industry leaders will discuss technical and commercial strategies to deliver gene therapy products to patients. See the full agenda and book tickets at https://celltherapy.knnlab.com/.

The Prime Medical Group: The Value of Medical Communications for Gene Therapy

With Cell Therapy Manufacturing & Gene Therapy Congress less than a week away, we spoke to one of the exhibitors presenting in Brussels:

“The Prime Medical Group is delighted to be presenting at next week’s Cell Therapy Manufacturing and Gene Therapy Congress. The congress will provide a forum for delegates to discuss technical and commercial strategies for cell and gene therapies.

The Prime Medical Group has worked extensively in this area, providing strategic communications support for several orphan drugs and rare diseases, as well as developing and implementing the communications programme for the only gene therapy approved in Europe.  Howard Sinclair (Strategic Director – Rare Diseases and Gene Therapy) and Andrew Jobson, PhD (Scientific Director – Rare Diseases and Gene Therapy) will present on Tuesday 3 February at 12:10pm. The presentation will focus on the importance of an effective medical communications strategy and plan, as well as the key considerations when bringing an orphan drug or gene therapy to the market to ensure optimal return on clinical studies investment.

‘This is an exciting opportunity for The Prime Medical Group to share our experience and expertise with some of the leading figures in the industry,’ Howard commented. ‘We have successfully partnered with pharmaceutical and biotech companies over the years and understand the challenges faced when developing an impactful communications programme for orphan drugs and rare diseases as well as gene therapies.’

In addition to presenting, The Prime Medical Group will also have an exhibition booth at the congress allowing delegates to discuss their specific communication needs with the team in more detail.”

Cell Therapy Manufacturing & Gene Therapy Congress is being held in Brussels on 2nd – 5th February 2016. See the full agenda and book tickets at https://celltherapy.knnlab.com/.  

The Prime Medical Group: Established in 1997 The Prime Medical Group is a leading medical education and communications agency, committed to creating outstanding medical education and communication programmes with global, regional or national implementation. To learn more their therapeutic experience or services visit www.prime-medica.com.

Cell Therapy: Three Predictions for the Future of the Industry

There is a palpable air of excitement and enthusiasm around the cell therapy industry and a sense that, as Christopher Bravery of Consulting on Advanced Biologicals, puts it: “cell therapy has taken off”.

There have been tremendous breakthroughs as the field has matured over the last 10 years, but we want to know what’s next: what exciting developments can we expect going forward, over the next 5 to 10 years? We put this to our panel of experts and these were their top 3 breakthrough areas:

1) Cures, not just treatments.

To date, most biopharmaceuticals offer treatment, not a cure. All that could be about to change: Jason Carstens, of the Fred Hutchinson Cancer Research Center, is excited about the advancements made in the CAR T-cells field. He says it’s mind-boggling that we are actually talking about a cure for cancer. He continues, “if I had a crystal ball and was looking forward to some potential breakthroughs, I would say it’s in the area of regenerative medicine where we have the ability to repair spinal cord injury for example, cartilage injury, bone damage, cardiac damage and really have a great impact on the quality of life for people.”

2) Cell kits: the microchip of the healthcare industry

John Rowley, of RoosterBio, says the future of our biotechnology healthcare products are going to incorporate stem cell technologies. For this to happen, stem cells need to be provided, very similarly to microchips, in formats that enable product development. He explains, “technology revolutions happen when kits come on the market. They allow anybody to gain access to a technology – making it easy to use, simple, affordable, and robust. Something that works every time.” Looking to the future he sees, “a day of a true stem cell reagent where you’re able to take out 50 million, 100 million cells from the freezer, thaw it out and use it directly in an experiment. And where that’s really going to be huge is the tissue engineering world.”

3) Improvements in Manufacturing Technology

Aby Mathew of BioLife Solutions, believes that over the next 5 to 10 years we will see developments on both the clinical and manufacturing sides. On the clinical side he expects that more therapies will get approval and we’ll know they’re working at the patient level.

On the commercial side, he sees that “manufacturers of these therapies will be able to optimize their processes a little bit better and also be able to drive the cost down, in combination with relationships with suppliers, who can now generate these tools and supplies on a larger scale.”

He hopes that the lower costs will mean that these therapies can reach a much wider patient population, whether you are in a first world or third world country.

Over 50 speakers and 200+ industry pioneers will be discussing the future of cell therapy at the Cell Therapy Manufacturing & Gene Therapy Congress in Brussels on 2nd – 5th February 2016. Join the conversation at https://celltherapy.knnlab.com.

Bringing Orphan Drugs and Gene Therapies to Market: Maximising ROI through an Effective Communications Plan

Businessman with business plan concept analysis strategy questions

Howard Sinclair, Strategic Director – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, and Andrew Jobson, PhD, Senior Editorial Manager – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, are talking at Cell Therapy Manufacturing & Gene Therapy Congress on Wednesday 3rd February in Brussels. Here they explain what they’ll be talking on:

“There are a multitude of urgent and critical areas to address in further developing your orphan drug or gene therapy to achieve the next milestone. They consume all your team’s energy, resources and time, and there never seem to be enough hours in the day. Against this reality, is creating a communications plan really that important? – Yes! Won’t the external communications just happen naturally anyway, as the relevant data become available? From decades of experience supporting everything from mega-blockbuster first-in-class agents, to very specialised medicines for the most obscure ultra-rare diseases, we would respectfully and emphatically answer: No.

Unique challenges exist for rare diseases, orphan drugs and gene therapies that require tailored solutions, distinct from standard approaches. Creating a robust, evidence-based, authentic and compelling scientific narrative is the starting point – and you will need a sound plan to effectively share this with potential product users, key influencers and the broader healthcare community. This could include clinical trial investigators, practicing specialty clinicians, primary care providers, nurses and payers.

An effective strategic communications plan is critically important, enabling you to optimally engage with your target audiences at the right time (which will likely vary over the course of the development of your asset) to achieve your immediate and long-term goals, whether it’s accelerating clinical trial accrual or ensuring optimal awareness and adoption into clinical practice upon market authorisation. Early development and initiation of a tailored, proactive and cohesive communications plan is arguably even more critical for orphan drugs and gene therapies to ensure your limited resources are most effectively channelled.

Topics to be covered will include:

  • Adding value to your product/clinical studies programme with a tailored medical communications plan.
  • Addressing the specific challenges for a medical communications plan in orphan drugs, rare diseases and gene therapy.
  • Driving the communications strategy through a focus on the unmet needs of both the patient and the healthcare professionals.
  • Defining the key elements of an optimal communications plan.
  • Making the plan happen – driving the initiation, management and delivery.

Creating a robust and tailored strategic communications plan is critical to success – we will explore the why, what and how.”

See the full agenda for Cell Therapy Manufacturing & Gene Therapy Congress and buy tickets at https://celltherapy.knnlab.com.  

Christopher Bravery: Justification for the Specification

Late last year we were fortunate enough to catch up with Christopher Bravery, Director, Consulting on Advanced Biologicals Ltd and a member of the ISCT EU Legal and Regulatory Affairs Committee. We asked him about the reasoning behind the topic of his talk ‘Setting Specifications’ at the Cell Therapy Manufacturing & Gene Therapy Congress on 3rd February 2016 in Brussels:

“I try and think of a topic that I don’t feel has been covered enough each year and choose that as my topic that I try and speak on. Particularly at the Cell Therapy Bioprocessing & Commercialization conference run by IBC in the U.S and Informa Cell Therapy Manufacturing and Gene Therapy congress in Brussels, because I think there are topics that somehow fall under the radar. The thing with justification of specifications is that you rarely have to write much during clinical development, and I often see ‘not applicable’ written for the justification in the specifications, which in many cases, the regulators will pay no attention to.

The ones that people are probably familiar in having to justify, are the things like endotoxin levels, where there is some reasonable guidance to what is a reasonable daily exposure to endotoxins, so you divide that by your dose and come up with a figure to justify the limit you’ve set for your endotoxin. Although, if you’re needing to do some sort of viral testing then it’s usually a no brainer that it is usually not detectable, and you don’t need to justify that specification much either.

Once you get to market authorisation, it is a substantial amount of work and text in the dossier, and I think what interested me when I thought about it was how it draws upon all of development. So I produced a figure actually where I laid out the CTD sections in a mind map, and showed all the links about the dative for justifying your product specification and where it will come from, and your data for your processes will come from.

Potency is a brilliant example of how do you justify your potency specification? It’s probably a bit easier for gene therapy than it is for cell therapy, but it is very difficult. That almost certainly might need to draw on non-clinical data as evidence that something sub-potent, that you’re not getting the effect you want, and that at another value on your potency assay is actually potent. Often the appropriate non-clinical models that might allow you to support that might be missing so you might be relying on in-vitro assays.

But really, I think the main reason I chose it is that in my consulting work I have seen a move towards later stage development.  There are certainly more companies thinking now about what they need for market authorisation, either planning or embarking on their pivotal studies. And really if you haven’t done the work on the process you’re taking into pivotal that is suitable for early commercial, then you would have an enormous amount of work to do in phase II. In phase III when you’re supposed to be validating the process, validating the methods and writing a dossier, all those things take a lot of time, so in phase II you really should have your characterisation of the process out of the way; identified your critical process parameters, your critical quality attributes and so on. But, there is always a lot to do!

What worries me is that this work might not be getting done, and then it would be very difficult to justify specifications when you have no data to base them on. Obviously if this is the case, then there is the pressure not to wait, but to get on with phase III, and so suddenly it’s done in parallel and you have six months to do what you really need two or three years for.

And this is why I chose that topic. It has really struck me as being something that we needed to start talking about – how you do that. What I have seen particularly with the cell therapy community, somewhat less with the gene therapy because it’s more like biotech, is really significant deficiencies in characterising the process and understanding what those critical parameters are. Without that characterisation data, you wouldn’t be able to justify those parameters.

I also have fears, as I’ve been through this myself, that decisions get made in corridors or at lunchtime about how you’re going to go about doing things early in development and sometimes if they don’t get recorded, then at the end you’re not sure why you even did it that way, let alone having a justification for the specification!”

Christopher’s talk is on day two of the Cell Therapy Manufacturing & Gene Therapy Congress at 16:00 on the Cell Therapy manufacturing stream, and no doubt will be extremely insightful. See the full agenda and buy tickets at https://celltherapy.knnlab.com/. We look forward to seeing you there!

Revolutionary Algorithm Mogrify Set to Transform the Field of Regenerative Medicine

mappingout
Credit: Nature Genetics & Rackman et al.

This week a paper published by a team of international researchers at the University of Bristol has sent excitement rippling through the cell therapy community. The team comprised of collaborators from Bristol, Australia, Singapore and Japan published the breakthrough last Monday (18/01) in Nature Genetics. They presented the creation of a predictive system (Mogrify) that can forecast how to create any human cell type from another cell type directly, bypassing the need for exhaustive trial and error.

The team led by Julian Gough have so far applied Mogrify to 173 human cell types and 134 tissues, outlining an index of cellular reprogramming.  Speaking about the breakthrough Gough, professor of bioinformatics, revealed to the University of Bristol that “the barrier to progress in the field is the very limited types of cells scientists are able to produce. Our system, Mogrify, is a bioinformatics resource that will allow experimental biologists to bypass the need to create stem cells”.

Secondly, when listing further achievements from the research, conducted in collaboration with Professor Jose Polo at Monash University in Australia, Gough confirmed that Mogrify had validated two new transdifferentiations. The algorithm succeeded first time in validating both of the new transdifferentiations, and it is this speed in achieving results that lends clear indication to the claim of Mogrify being revolutionary. Professor Gough added that he hoped “Mogrify will enable the creation of a great number of human cell types in the lab”.

This is a huge result for the regenerative medicine field and will no doubt speed up advances in life-changing medicines. Particularly, the ability to produce a number of types of human cells will directly lead to new tissue therapies, and a much improved understanding of cell production at a molecular level. One hope going forward is the potential to grow whole organs from someone’s own cells.

For five years Gough collaborated with Dr Owen Rackham to create a computational algorithm to predict the cellular factors for cell conversions. This was achieved largely in thanks to data collected as a part of the FANTOM international consortium, of which Gough is a member.

To highlight the size of the achievement, it must be remembered that scientists have only been able to discover conversions of human cells a handful of times since Japanese researcher Shinya Yamanaka created the first human artificial pluripotent stem cells in 2007.

The algorithm has been released and made available online for others to use, so that the field may advance at a much faster pace.

The paper ‘Mogrify: An Atlas for Direct Reprogramming Between Human Cell Types’ by Rackham et al in Nature Genetics.

Challenges Facing the Cell Therapy Community – And how to Overcome those Hurdles

It’s no surprise that cell therapy companies face a myriad of hurdles when developing a product from bench to bedside.

The range of challenges can sometimes feel overwhelming – even for the most seasoned pros in regenerative medicine. So we set out to ask some of the leading names in the industry what some of the biggest hurdles are, and what can be done to overcome them.

Aby Mathew Ph.D., Senior Vice President and CTO, BioLife Solutions.

Aby believes one of the biggest challenges is that companies set up their processes for clinical feasibility, not necessarily commercial viability. ‘So they’re focused on, does the therapy work, not necessarily can we scale it up, can we make it economically viable, can we deliver it globally?’ Aby says.

So what’s the solution? Aby believes it’s down to human capital and mass manufacturing: ‘Down the road, what they might look to do is automate their processes, so instead of having a manufacturing process that might take 50 or 100 people, they might be able to implement a machine that can reduce the head count, but can also reduce the possibility of human error.’

Another solution, Aby says, is to buy in bulk. ‘In the manufacturing process, things such as media components, instruments that you have to use, or components where its packaged up, all of those end up adding to the individual cost. But when you go and buy that from your suppliers, you’re going to get a much better price if you order 1,000 units rather than 10 units and that’s really where that scale-up starts showing the cost of goods benefit.’

Jon Rowley, Ph.D., Chief Executive and Technology Officer, RoosterBio, Inc.

Jon Rowley agrees. He believes a big challenge that many companies have is being able to manufacture products at commercially relevant lot sizes while maintaining all the quality parameters of the cells. ‘They need to make sure that those stem cells don’t lose the biological functionality that they have that makes them therapeutic in the first place. And during scale-up, this can definitely be lost if you’re not looking at the right things,’ Jon says.

His solution? Jon says companies need to understand what the quality parameters are, get the technologies in place to manufacture at a much larger scale, and then manufacture these cell therapy products at costs that enable companies to go to market with them and actually have a profit left over at the end of the day.

Julie G. Allickson, Ph.D., Director, Regenerative Medicine Clinical Center, Wake Forest Institute for Regenerative Medicine

Julie Allickson notes that regulation and due process can pose a challenge to many companies. She advises, “moving to regulatory approval in an efficient manner means really early discussions with the FDA, being able to share with them your knowledge in regards to the technology, and to be able to get their input.” She adds there are several opportunities to talk to the FDA along the way that companies should take advantage of in order to make the process run as smoothly as possible.

Discover more technical and commercial strategies to deliver cell and gene therapy products to patients at the Cell Therapy Manufacturing & Gene Therapy Congress. View the agenda and buy tickets here: https://celltherapy.knnlab.com/