GSK's Biopharm Plans

By Cliff Mintz Ph.D.

Like many other big pharma companies, GlaxoSmithKline (GSK) failed to recognize (until recently) that its future growth would likely be linked to development of innovative biotechnology-based products. Recognizing this, in 2008, the company created a new division called the Biopharmaceuticals R&D Unit, with the goal of becoming a global leader in the biopharmaceutical market. The company hopes that by 2015 20% of its drug development portfolio will be biopharmaceutical products.

Early on, GSK executives realized the company needed a fresh, new approach to drug discovery and development if it wanted to achieve the ambitious goals it set for the biopharmaceuticals R&D unit. Thus, rather than appoint a “company insider,” GSK chose Ian Tomlinson, Ph.D., a former academic and successful biopharmaceutical entrepreneur, to head up the newly formed biopharmaceuticals R&D unit. He is currently senior VP and head of biopharmaceuticals R&D and sits on GSK’s R&D executive committee.

What Scientific And Business Considerations Contributed To The Creation Of The GSK Biopharm R&D Unit?
Admittedly, GSK came late to the biopharmaceutical game. While the company dabbled with a couple of monoclonal antibodies (mAbs) in the early 1990s, it wasn’t until 2004 that GSK made a concerted effort in biopharmaceuticals by setting up an R&D group mainly focused on mAbs for certain novel targets.

In 2007, GSK acquired an antibody-derived fragment company called Domantis Ltd. for $450 million. I founded Domantis in 2000 and joined GSK after the acquisition. In late 2008, GSK decided to consolidate all of the company’s activities in biopharmaceutical R&D into a single unit — the Biopharmaceuticals R&D Unit — and I was tapped to head it.

The decision to focus on biopharmaceuticals R&D — mostly mAbs and domain antibodies (antibody-derived fragments) — was driven by the enormous diversity offered by biopharmaceutical drugs and the improved safety and efficacy that large molecules frequently demonstrate over small-molecule drugs. Rather than attempting to discover the next blockbuster for a single indication, the diversity and flexibility offered by biopharmaceuticals permits us to develop novel, safer medicines for indications that span multiple therapeutic areas.

Unlike many of our competitors (who use a matrix and vertical approach to drug discovery and development), GSK Biopharm essentially controls (owns) development of new drug candidates from discovery through commercial launch. To that end, the Biopharm R&D Unit leverages its expertise in biopharmaceutical drug discovery, formulation, delivery, process development and manufacturing to bring new drugs to market. In contrast with many of our competitors, we typically don’t have therapeutic-area expertise within the Biopharm R&D unit. Instead, we look to partner with company therapy area experts who are charged with prosecuting molecules for specific disease indications.

A good example of this is an anti-IL5 mAb called mepolizumab that is in a Phase 2b clinical study to treat severe asthma. While the Biopharm Unit looked after discovery, process development, and manufacturing for the molecule, we handed off mepolizumab to the respiratory disease folks who have many years of experience designing and managing clinical trials for asthma and related respiratory disease indications. To some, this may resemble something akin to the relationship between a CRO and a pharma client, i.e. you hand off the molecule to a third party, and then it comes back to you for further development. But, in reality, the relationship between the Biopharm R&D Unit and therapy area experts is a true partnership; both parties are focused on bringing their collective expertise to bear to commercialize a new product for the company.

This approach tends to prevent duplication of effort within the company and across different units, and it allows us to leverage the deep therapy expertise that has been built over the years at GSK. It also helps to prevent duplicating or creating new jobs (which we don’t necessarily need) and allows us to function more efficiently and cost-effectively.

Does The GSK Biopharm R&D Unit Operate Much Differently From The Biotechnology Divisions Of Some Of Your Competitors?
Although I haven’t worked for any of our competitors, I believe we operate differently from most other biopharmaceuticals R&D units. For example, every molecule we are investigating in the Biopharm R&D Unit is assigned what is called a “medicine development leader” or MDL.

The MDL functions a bit like a biotechnology company CEO; that is, each MDL has sole responsibility for a particular molecule from discovery to commercial launch. MDLs oversee a diverse group of individuals whose primary function is to commercialize a particular asset. Members of the group may hail from the biopharm unit, therapeutic area groups, or regulatory side of the organization (which is kept separate again). The goal of this team is to insure that we do everything possible to direct the asset into every disease indication where it can potentially make a difference for patients.

These people (MDLs) know their molecules inside and out and truly understand the biology surrounding a particular asset. Their primary responsibility is to work closely with all GSK therapy group leaders to determine whether or not certain molecules may be useful across multiple therapy indications. Over the past two years, we have successfully applied this model to identify additional therapeutic indications for many of the assets that are currently in development.

Because MDLs play a pivotal role in our development process, they must have exceptionally strong scientific backgrounds and outstanding leadership and management skills. We want to get the most that we can for each and every molecule that we attempt to develop.

We think our model is a good one because it tends to empower individuals to do what is in the best interest of a particular asset. In other words, there is usually a single person (not a group) in the company who is ultimately accountable for making an asset fly or fail. Consequently, there is a lot of responsibility on these people’s shoulders, which is why you have to have very strong leaders in the MDL roles.

The emergence of an empowerment culture at GSK is very consistent with the MDL model of drug development. Other companies, where personal empowerment isn’t encouraged or embraced, may find it more difficult or impossible to allow a single person to have overall responsibility and control of an asset that potentially could be a multibillion drug. I think the MDL model works because it tends to empower people who actually know the “ins” and “outs” of a specific asset to make the right decisions about its development. At other companies, these decisions are frequently made by executives who really don’t understand the science or biology of individual models. This isn’t necessarily good because, in the end, it is the science that ultimately drives the success of the medicines that we develop.

Because of the emergence of an empowerment culture at GSK, we are beginning to attract and hire more people with an entrepreneurial way of thinking about drug development. This is markedly different from the traditional types of persons hired into R&D positions at most pharmaceutical companies.

GSK is a company today where personal empowerment and ownership is a big piece of what we do on a day-to-day basis. There is no one constantly looking over my shoulder or second-guessing me or telling me what to do — I wouldn’t be working for GSK if it wasn’t like this. I have to say that GSK is a very interesting and fun place to work. In fact, I am having a lot more fun than I ever expected to have while working for a major pharmaceutical company!

Which Therapeutic Areas Will The GSK Biopharm R&D Unit Focus On?
We are somewhat agnostic in determining which therapy areas that the biopharm group will focus on. Remember, as recently as five years ago, GSK was mainly a small molecule company with almost no expertise in biopharmaceutical drug development. Consequently, we will partner with any group at GSK that thinks their target or disease area may benefit from any of our biopharmaceutical drug development candidates.

Admittedly, it has been somewhat challenging to get an organization with a small molecule focus to begin to consider large molecule solutions for certain indications. However, we have partnerships with all therapy areas across GSK, and interest in biopharmaceutical approaches and solutions is growing. Our goal is to provide drug development options by offering our partners biopharmaceutical alternatives to historically small molecule targets.

In the end, it is all about having choices and developing the best drug to treat diseases and help patients. Also, developing a biopharmaceutical capability allows GSK to diversify its business base and move into new therapy areas and markets. That said, diversification is a good way to manage the huge risk typically associated with new drug development. Ultimately, we are trying to create an organization that is no longer exclusively reliant on blockbusters and focuses more on so-called niche products.

Will The Products Developed By GSK Biopharm R&D Unit Mainly Focus On mAbs And Antibody-Derived Fragments?
The remit for the biopharm R&D unit is to develop therapeutic peptides and recombinant proteins expressed from tissue culture cells. Today, 85% of our product development portfolio is mAb or antibody fragment-based molecules. Much of the current portfolio came from the Domantis acquisition and in-licensing deals with other companies. However, there is a slice of the pie that will include recombinant cytokine molecules, therapeutic peptides, and other molecules. For example, we currently have a product in late stage clinical development called albiglutide, a GLP-1-human albumin fusion protein to treat patients with Type-2 diabetes. That said, there is nothing stopping us from growing the nonantibody part of the pipeline. However, today our greatest opportunities lie with mAbs and antibody-fragment products.

GSK Recently Announced It Intends To Create A Division To Develop Treatments For Rare Or Orphan Diseases. Will The GSK Biopharm R&D Unit Play A Major Role In This Effort?
The rare diseases unit is focused on understanding niche indications, and, if a large molecule solution makes sense, we will certainly get involved in the mix. Put simply, the GSK Biopharm R&D Unit is there to support them or any other therapy areas within the company that believes our products will be useful.

I believe many of the mAbs and domain antibodies in our current development portfolio may be useful to treat certain rare diseases. And, to that end, we are beginning to explore their uses for certain rare disease indications. But, again, it is important to point out that expertise for these indications resides within the rare diseases unit, and the biopharm unit’s contribution is to determine whether the biology of some of our development candidates supports their use as a possible rare diseases treatment.

I want to stress that any GSK development group can come to us and request that we create or develop potential biopharmaceutical products for their targets. It’s really about letting the rest of the organization know about our technology platform and the opportunities offered by the biopharm R&D unit.

What Is GSK’s Position On Biosimilar Products?
Let me say that the number one focus at the GSK Biopharm R&D Unit is developing innovative (not generic) products. However, GSK does, in fact, support a regulatory framework for development and commercialization of biosimilars, but with two caveats.

First, biosimilar product development must be exclusively science-driven, and patient safety for these molecules must be guaranteed. Second, the regulatory framework that is ultimately put in place (in the United States) must allow innovator companies to continue to develop improved second-generation molecules (or so-called “bio-better” products) despite the general availability of first-generation biosimilar medicines. It would be a shame if the availability of biosimilars hinders development of new and improved innovator products.

For example, a fairly substantial number of patients with rheumatoid arthritis either don’t respond favorably or stop responding over time to treatment with available anti-TNF medicines. It is conceivable that availability of biosimilar versions of these drugs (to which most patients respond) may dampen investment into development of new agents to treat rheumatoid arthritis. That said, the new legislation being considered in the United States seems to strike a fair balance between development of innovator and biosimilar products.

As far as development of biosimilar mAbs is concerned, I want to point out that Abbott’s Humira (a monoclonal antibody treatment for rheumatoid arthritis and other inflammatory diseases) is predicted to be the biggest selling biologic on the market by 2015. In light of this, I suspect that development of biosimilar mAbs may not be that far off. In fact, over the next few months we expect to receive guidance from the European Medicines Agency regarding the regulatory requirements for approval of biosimilar mAbs.

What Do You Think Will Be The Next Big Leap In Technology Or Innovation In The Biopharmaceuticals Space?
Over the past 15 years or so, therapeutic mAbs have dominated the pharmaceutical markets. Six of the top 10 best-selling biologics in 2015 are expected to be mAb-based products. With this in mind, I think the next big innovation will be the development of highly specific antibody fragments — which have the same biological properties of mAbs but are much smaller — that can be directly delivered to the anticipated site of action in patients.

For example, we are keen on developing domain antibodies that can be directly inhaled into the lungs of patients suffering from various inflammatory lung diseases. This makes a lot more sense than relying on systemic administration of mAbs (with likely systemic side effects) to treat disease that is localized to the lung. Another area of interest is the topical delivery of mAbs and domain antibodies through the skin or mucous membranes.

Ultimately, I believe the industry is moving toward development of drugs with greater target specificity and more targeted delivery strategies. This will likely culminate in the development of safer and more efficacious products. This won’t happen overnight, but it will happen!