Bertil Lindmark is the current Chief Scientific Officer and Executive Director of R&D at Almirall and member of Almirall’s Management Board. He has been in this position since January 2011 and in that time filed aclidinum bromide in the Genuair inhaler device for the treatment of COPD in EU and in the US 2011, as well as filing linaclotide for the treatment of IBS-C in EU 2011. Both filings were approved in 2012.
Prior to this, Bertil held the position as VP and Head of Clinical Development AstraZeneca Japan, with cross-therapy area accountabilities 2009-2010. He also worked as VP Clinical Development Respiratory and Inflammation Therapy Area in AstraZeneca 2001-2009. Developed Symbicort and Symbicort SMART therapy, and was accountable for taking more than 25 NCEs into man.Between 1991 and 2001, he held clinical roles in Astra and AstraZeneca, with drug development experience from all phases and all geographies, covering mainly respiratory, gastroenterology and rheumatology.
In this interview Bertil Lindmark praises the manoeuvrability of smaller pharma companies. He argues that the current in vivo models need revising and that single-point interventions may not be the best strategy for pharmaceuticals
Pharma IQ: I read on your website “the division of Almirall is to be recognised as an innovative pharmaceutical company and be placed, among the top players of strategic, therapeutic areas with a strong European presence and global reach.” How are you demonstrating this innovation at Almirall and what lessons in innovation could bigger pharma companies learn from you?
Bertil Lindmark: Looking back I think it's been pretty amazing because Almirall has been on a journey from being a fairly local company to actually becoming the second pharma company in the world to get a long- acting antimuscarinic approved.
This was probably a surprising feat because we are the first and only company who have achieved approval both in the US and in Europe more or less on the same day with just one review round in both geographies. So I think that was a good demonstration of actually being innovative and at the forefront of both quality and quantity of data, getting that approved. In particular, novel inhalers have been difficult, but the Almirall Genuair TM multidose DPI was not questioned on either side of the Atlantic.
Pharma IQ: What could big pharma organisations learn from small-to-mid-sized organisations like Almirall?
Bertil Lindmark: It's a bit presumptuous of me to say what the big pharma should be learning. From my general experience the big pharma organisations are starting from their own particular point, in a way, because the organisations are so big and voluminous that I think they may find it difficult to sustain their large organisations.
The cost base will make it very difficult to find any medicines which may really sustain the huge organisations. They're caught in a trap of their own size and therefore, as we have seen for the last decade, it's been difficult to move away from the blockbuster concept. And, of course, for Almirall, we can find a value sector which is completely different compared to the bigger companies.
And then being small has a value in itself. I can get access to all my direct reports on the Barcelona site within ten minutes. I also have very easy access to the German sites. And obviously with a small company where you have the main shareholder taking a very active leadership role, having built the company for many years, and being very accessible, I think the distance to key decisions and decision makers is really short.
Compare this to when I was working in AstraZeneca, the company had much more resources in many different areas but, at the same time, the distance between the decision makers and the distance to the owners of the company was much greater.
Pharma IQ: In a recent interview the CEO of Novartis said that big pharma business models needed updating. What are your thoughts on this as a definition of the blockbuster changes?
Bertil Lindmark: I think the big pharma model and the blockbuster model has been outdated for a few years now and obviously the big pharma sustainability will continue to be challenging.
We can see now that the world pharma market is leaning heavily on the US market. And even in the US you can see the beginnings of demands on more comparative efficacy and the pressure to lower drug prices, to make medicines affordable. So I think the big organisations where you have everything integrated, will have an increasingly difficult time to actually be sustainable. And again we can see the level of innovation and the actual output from the big organisations is not impressive, with a few exceptions.
When I was in AstraZeneca we increased the number of candidate drugs from ten per year to 28 per year, but actually the output of real medicine didn’t increase. So there are a number of problems for the pharma industry and the biggest problem I think is the lack of correlation between animal data and clinical data.
Late last year there was an article looking at the human immune system versus that of rodents. They could see that even though the molecules that were involved were more or less similar, in many cases one type of signalling in the rat was completely opposite to the signalling going on in man. And this is obviously fundamental. If you start from the wrong assumptions with regard to biology then, of course, you will have very little success in man and then the numbers game cannot really help you.
So I think one of the biggest problems for all pharma, is there is such a low degree of correlation between animal experiments and experiments in man.
The other problem is that the key human diseases like cancer or rheumatoid arthritis are very complex, and much more complex than we would like to believe. And cancer is a multisystem, continuously-reprogramming disease where you cannot do single-point interventions so it's unlikely that single agents will confer huge therapeutic success.
And therefore many of the assumptions underlying the numbers game and the specific assumptions of successes in key disease areas like cancer, I think they are not real. In order to make real progress we need to think multi system and the assault will have to be combinatorial rather than single target. Can big pharma change to a new paradigm like this? I am not sure.
Pharma IQ: In the UK recently the Chief Medical Officer, Professor Dame Sally Davies, warned that antibiotic resistance is growing at such a pace where we might actually face a future where there mightn't be cures for infectious diseases. In your opinion what do pharma companies need to do, or, indeed, small biotechs, to start basically reversing the situation?
Bertil Lindmark: With the advent and the innovation of antibiotics, we’ve being blessed for a period of time where we've been able to counteract many of the bad bugs that are out there. But it's only a matter of time before the bacteria get the upper hand and obviously this is a quest for mankind forever, I think. So there have got to be the right incentives and the right support systems for companies to remain interested in continuing developing drugs in the infection area.
I think the pharma industry has been investing then divesting then starting to invest again and I think we cannot stop investing because it's a never-ending quest. Apart from the measures to reduce the uses of antibiotics and the measures to eliminate the biological sources of multi-resistant bacteria, we will continue to need new antibiotics for the foreseeable future. The companies need to understand this, and then society needs to help the pharma industry to continue that effort because if, of course, the prices of antibiotics go to zero then the pharma companies will not be interested in investing.
Pharma IQ: What do you see as the biggest challenges in drug development right now?
Bertil Lindmark: I think the biggest challenge in Europe at least is pricing and reimbursement. There is no overarching philosophy or policy in Europe. There is a lack of coherence, consistency and coordination from one country to another, at least in Europe. In the US, of course, the pricing and reimbursement is freer and there are other games going on. So I think the pricing reimbursement and the market access at this point in time is becoming a difficult sector for the industry to tackle.
Pharma IQ: Bertil, what changes do you predict to occur in medicine in the next ten years?
Bertil Lindmark: In terms of diagnostics, I think the human genome understanding will increase, because the human genome was already covered and understood at least from a component point of view in 2003. And I think we did underestimate the complexity of this machine because it's an auto-reprogrammable, forever changing machine and just because we know the components, it does not mean we know the dynamism and the reprogramming changes.
I think even though there will be more understanding of the genetic set up and the genetic subgroups in different diseases this will still be a marginal part of the overall medicine delivery, but still the access to genetic information is going to be the biggest trend in the next few years.
A different trend may come from orphan diseases or complex immunological diseases, or cancer. In some few individuals or some institutions may be able to pay the full cost of detailed biological work-up and in these cases the depth of biological insight for the individual will accelerate dramatically. The knowledge reaped from the detailed study of individual patients with severe disease will bring light and eventually therapeutic benefit to the larger audience of patients.
Another trend is the shift from governmentally sponsored and governmentally paid medicine to medicines that are going to be paid for by individuals. And then, subsequent to that, there is a trend for pharma industry to understand how they can cater to the masses, to the needs of the masses and still make money. And I think these are the two three biggest trends that I can see.
Pharma IQ: You were VP and Head of the Clinical Division at AZ in Japan before you came to Almirall. What developments do you predict to happen in Asia, say between now and 2020?
Bertil Lindmark: When you look and listen to the Asian sub-region you get the impression on the one hand everything is growing super-quick, and then on the other hand China's economy is blown up in an artificial way, and the Japanese economy is looking frail and then you have the geopolitical conflicts between North Korea and South Korea and between China and Japan, so the pharma perspective maybe overwhelmed by the geopolitical, the economical and the conflict perspectives in Asia.
At the same time we can see that there is an increasing number of consumers that can afford western medicines and, but at the same time, China's market for western type of therapeutics is the size of the Italian pharmaceutical market.
From my perspective Japan will continue to be very important and obviously, with the growing number of old people in Japan I think we'll see continuous increase in demand in Japan. And I think that will be the most important market to watch for pharma companies still.
Pharma IQ: So you would say Japan would be more of an area to watch than China?
Bertil Lindmark: Yes, I think pharma companies that want to gain great benefits from the medication market; Japan will really continue to be the overwhelmingly biggest market and the most important place to be.
Pharma IQ: What’s you view when it comes outsourcing to CRO?
Bertil Lindmark: We are outsourcing to a very great extent and we have coined what we call the SMART pharma concept, because I don’t believe that we should grow in numbers but we should grow in leverage and creativity, innovation and value rather than number of people.
We're working with PAREXEL and Quintiles and a number of other CROs. Obviously there is a relationship between quality and price and quality and there is also a perhaps a concept of, you know the old saying of buying from, buying IT services from IBM; nobody can complain or question your choosing the quality brands, so to speak.
I think there is a leap of faith if you want to go with unknown CROs. They need to prove themselves a bit. And obviously that leap of faith and the distance between the perception and the perhaps more high quality delivery of, these companies make there, there's got to be a price reduction.
When we look at the prices for CRO services we can see that while we can find some smaller companies, they are not actually that much less expensive than the large CROs. Therefore I think we'd rather work with a few companies than spread to many smaller companies.
Pharma IQ: What services you are most likely to outsource to a CRO?
Bertil Lindmark: We outsource parts of regulatory, parts of filing, the running of clinical trials, toxicology and microbiology. We outsource parts of research with regards to chemistry and with regards to some of the pre-clinical testing. So generally speaking we are unafraid of outsourcing and we like to focus on the areas where we actually make a difference, and where we can add creativity and uniqueness.
Pharma IQ: Looking towards the financial backing of your organisation, what do you find are the biggest challenges when it comes to capital and how is an organisation like Almirall being funded?
Bertil Lindmark: Historically we’ve been funded either through internal economy or with partners. We partner the development of the respiratory series with Forest Labs. And we also did a deal with Ironwood, where they actually funded the Phase III of linaclotide. It's the first medicine for IBS C that has been approved in Europe and the US and where we took care of the regulatory phase and the setting up the clinical trial programme from a European perspective.
We work with partnerships when necessary to get our programs funded. In Spain, we have some governmental mechanisms to achieve funding and we have started working with VC-based companies like ASLAN Pharmaceuticals.
We intend to continue exploring the different funding opportunities depending on our internal economy and finances because we would like to drive the projects as far as we can and obviously get as much value as we can.
Pharma IQ: What's next for Almirall? Is it growth or an increase in geographical bandwidth?
Bertil Lindmark: Historically we used to be very Spain-focused, and I guess going back I think in 2002 22% of our total, overall sales were generated outside of Spain. In 2014 we believe that >70% of the turnover will be from Europe and the rest of the world. So we, what we want to do now with the approvals of Eklira and the, presumably of the combination of aclidinium bromide and formoterol in a couple of years' time, we want to expand geographically. We are in the process to do so. We have established a marketing company in Canada. We’re looking for opportunities in South America and we are expanding either directly or with partnerships in different parts of the world.
Another example is the increased strengthening of the respiratory franchise. We have probably one of the best dry powder inhalers in the industry and we are looking towards a number of pre-clinical candidates in the respiratory area, mainly anti-inflammatories for COPD. In addition we have what we called a MABA estate; that is several inhaled compounds with both antimuscarinic and beta2- agonist properties. These can be used as the foundation for what we call triple combinations (two bronchodilator mechanisms and one anti-inflammatory in one presentation). So that's one area, the respiratory.
Another area is our interest in dermatology. We do have a derma business that is growing nicely. We're number one in Germany in dermatology and we're number eight in Europe in dermatology. So this is a part we want to continue to build on and strengthen both with our own compounds, with repositioning of compounds and with business development. The respiratory therapy area and dermatology will be the mainstay, but we also have interest in GI and in pain. So I think we're at a very important stage in Almirall where we can see the geographical expansion and the therapeutic area expansion starting.
Pharma IQ: Bertil, we wish you the best of luck with your business.
This interview was conducted by Niamh Madigan