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Interview: Ending the haemophilia drug shortage

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Jaymin Amin, CEO of ProFactor Pharma (PFP), discusses the company’s life-changing, and life-saving, work.

PFP says it has developed a low-cost production process for creating human factor VIII (rhFVIII), a complex protein which induces blood clotting and is used to treat haemophilia A.

There is a severe worldwide shortage of rhFVIII and PFP has developed a patent protected way to make the protein in a bio process that delivers significantly higher yields than the industry standard.

Jaymin Amin has more than 20 years of sales, marketing and financial experience in life sciences start-up companies. He joined the board of PFP in 2011 and became CEO in 2017.

The company completed a £2m seed funding round in the summer of 2019,  lead by the investment syndicate Kelvin Capital and supported by Ingenza Ltd, to optimise the PFP process and complete pre-clinical toxicology studies.

HTW: Why was the business founded and how have you developed since then?

JA: The three original founders, Professor John McVey, Dr Ian Garner and Richard Cruse, first worked on a Factor VIII project in the late 1980’s at Delta Biotechnology in Nottingham. Further experiments were continued at PPL Therapeutics in Edinburgh. None of these were successful but they all thought, given the enormous value of Factor VIII, that, once the patent landscape permitted, we should try another approach.

Factor VIII (rFVIII) is probably one of the most expensive compounds in the world, gram for gram more expensive than diamonds, gold, oil and most other drugs, so clearly a great business opportunity. With John’s experience in the field, we also knew that the existing producers had limited capacity to make enough to treat everybody that needed it.

In fact, to treat the whole of the haemophilia sufferers in the world at the same standard as the west, we would need to make more than 30 times more product – demonstrating the enormous undersupply in the market. And, as you can  imagine, treatment is expensive. 

During his research programs, Professor McVey had demonstrated a way of vastly improving the expression of Factor VIII using something called codon optimisation. That means that the genetic instructions for cells to make Factor VIII were much more efficiently processed.

That led the way for John to develop the high expressing cell-line in the laboratories of Ingenza, which was then optimised through selective cloning at PFP’s own laboratories at BioCity Glasgow. The development of the relationship with Ingenza was hugely important to the development of the company. Ingenza became a significant partner and facilitated the continuing development of PFP. 

Making recombinant proteins is a bit like brewing. Yeast is the cellular organism used for this because one of the properties of yeast is that is converts (consumes) sugar and turns it into alcohol. The cellular organism we use carries an extra gene which carries the instructions for making Factor VIII. The cells are then “brewed” in a nutrient enriched medium and naturally multiply (just like yeast) and follow the genetic instructions to express Factor VIII into the liquid medium. 

Final lab-scale optimisation of the upstream (fermentation) and downstream (purification) was also undertaken under contract with Ingenza leading to the extraordinary results we have in the productivity of the process.  

HTW: Tell us about the life-changing, and indeed life-saving, work you’re doing

JA: Haemophiliacs have a genetic deficiency for making Factor VIII, which is vital in the coagulation cascade which results in the sealing of a ruptured blood vessel. It’s important to understand the wonderful sophistication of the human body.

Sometimes, you wonder “where did that bruise come from?” and that’s just the bleeds you can see. The body is repairing little bleeds all the time. But not for the haemophiliac. For them, their problem results in spontaneous bleeding into muscles, joints and internal organs. Without treatment, haemophiliacs typically die of organ failure in their teens.

Prophylactic treatment, which is the norm in the western world, replaces the Factor VIII the body is not making allowing for a normal life. There are famous sportsmen who demonstrate this, Alex Dowsett, for example, a wworld class professional cyclist who won a silver medal in the 2010 Commonwealth Games and was in the 2021 Italian Giro.  

Elsewhere, however, people aren’t so lucky. Haemophilia is not only fatal, it is a painful and debilitating condition. Most of the world’s treated haemophiliacs only get emergency treatment, when they have to go to hospital following a serious bleed. So, if they survive into adulthood, they tend to be crippled with painfully damaged joints.

PFP has developed a way of making recombinant Factor VIII which, we believe, is much more productive and efficient enabling us to address both the availability and the pricing of treatment. 

(Centre) Jaymin Amin from ProFactor Pharma

HTW: How badly is better haemophilia care needed?

JA: What we have appreciated in studying the market data available over the last 10+ years is that more than 2/3rds of the haemophilia A patients continue to get inadequate or, indeed, no treatment at all.

This is fundamentally because of the lack of available product coupled with the high prices charged by the few manufacturers of the recombinant product. Not forgetting, of course, plasma derived product, the subject of the devastating “tainted blood” debacle of the 1980’s and 90’s causing many people, not just haemophiliacs, to be infected with HIV and hepatitis C.

Nevertheless, plasma derived Factor VIII is still made with much more rigorous purification processes being imposed. This, in particular, reduced the quantity of Factor VIII coming from plasma.

But, together with the obvious limitations in the supply of suitable plasma – donations – plasma derived Factor VIII is also in short supply. Plasma, over the last 10 years, provides about 3.5bn International Units (IUs) per year which represents about 30% of the total quantity of Factor VIII used.

Treatment in the UK and, indeed, in the Western World, is good. Usage in the UK is. on average, around 90,000 IUs per patient per year. Compare this with India (20,000) or China (22,000) or South East Asia (35,000) and then the USA (160,000).

In fact, the USA uses almost 20 per cent of all the available Factor VIII. Indeed, 80% of the worlds supply goes to just 14 of the richest countries in the world, there are 195 countries in the world. 

According to the latest estimation by the World Federation of Hemophila, there are about 660,000 sufferers of Haemophilia A. And from the same source, we understand there are about 190,000 treated. Of these, we estimate, again from the WFH data, that half of these get, what the WFH refer to as “inadequate” treatment.

But that leaves 470,000 patients untreated. I think that speaks to your question as to the huge unmet need.

HTW: Your process for making rhFVIII sounds like it has huge potential – what are the possibilities?

JA: The process is so productive that a single 2,000 litres fermentation, the scale of current stainless steel systems, produces around 400 million International Units (IUs) of high purity Factor VIII.

We plan to have multiple runs per year building to 3bn IUs per year. That’s almost as much as the plasma derived market in total! This would translate into sales of £450m per year.

The significance of the productivity and the use of single use/disposable technology is that it gives us a very low cost of goods which is why we will be able to provide treatment to those regions currently locked out by virtue of price. And the importance of the process technology approach is that construction of a manufacturing facility is much cheaper.

So, essentially, the sky’s the limit! The process is capable of being replicated anywhere in the world which would clearly benefit developing counties like India, China and South East Asia, which are also probably the biggest markets in the world.

For the UK, there is a tendering process where we believe we can beat anyone else on price. And that’s 600M IUs per year or £100m in sale.

HTW: Progress with clinical trials – have they begun yet? 

JA: We are currently in the process of a Series A fund raise that will enable us to commence human clinical trials. We have completed the pre-clinical toxicology study successfully.

HTW: What is next?

JA: To complete the £30m Series A fund raise to enable us to manufacture material for clinical trials, undertake the abridged regulatory clinical trials, and manufacture product for first sales in 2025.

HTW: What are the long-term outlook for the business – what is the ambition?

JA: The aspiration of the business is to provide treatment to the 70 per cent of the worlds Haemophilia A sufferers who are currently untreated, by offering an affordable and accessible recombinant FVIII, while delivering outstanding returns to our shareholders.

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