Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘drug discovery’

mimabs_logoOne of the partners of the Marseille Immunopôle cluster is an immuno-technology center focused on translational research called MI-mAbs (“MI” for Marseille Immunopole, and “mAbs” for monoclonal antibodies).

It aims to bridge the gap between industry and academia by accelerating the development of novel monoclonal antibodies for new targets.

MI-mAbs is based in the Parc Scientifique et Technologie de Luminy.

It’s a stone’s throw from the Centre d’Immunologie de Marseille-Luminy (CIML), which this year celebrated its 40th anniversary (1976-2016).

Panoramic view from CIML

Panoramic view from CIML

Luminy is also the home to several companies focused on immuno-oncology, including Innate Pharma and HalioDx. Marseille has the ambition to become a world leader in the development of immune-based therapies

MI-mAbs is funded by a €19M award from the French Government, as part of their Investissments d’avenir/Investments for the Future program.

The Scientific Director of MI-mAbs is Professor François Romagné. He’s a co-founder of Innate Pharma and for 14 years was the company’s Chief Scientific Officer (CSO). He’s one of the inventors of lirilumab and monalizumab, both of which are in phase 2 clinical trials.


Professor Romagné kindly spoke to BSB about MI-mAbs and how it plans to accelerate innovation and develop new drug candidates for the treatment of cancer or inflammatory disease.

For our French speaking audience, here is a brief excerpt from the interview with Pr. Romagné, where he introduces himself and MI-mAbs.

It’s an incredible time for immunologists like Prof Romagné, where the clinical results we are seeing with new cancer immunotherapies have validated a lifetime of work.

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According to a forthcoming article published in Forbes, excerpts of which appear on Matthew Herper’s blog “The Medicine Show,” big pharma should take bigger risks and outsource R&D to smaller, innovative companies.

At least that’s the philosophy of Bernard Munos, the former Lilly sales executive who has focused on the innovation problems faced by the pharmaceutical industry. According to Forbes, he believes that big pharma should “cut research and development” and “rather than do research in house, companies should close their labs and outsource the work to tiny, nimble startups that can explore bigger, crazier ideas.”

However, as Munos goes on to say in an excerpt published by Matthew Herper:

“You cannot script innovation,” Munos says. “You cannot boil it down to a code of best practices. Because it is unpredictable and the opportunities in science do not match the opportunities in markets.”

That is why Munos’ strategy of outsourcing drug discovery may not be the right one – there is no formula that you can give a vendor on how to be innovative.  Indeed, leveraging the innovation of small biotechnology companies is nothing new – isn’t that what big pharma already does with its licensing deals and alliances?

The question that comes to mind from the provocative Forbes article is whether innovation of drug development is a service like clinical trials that can be outsourced? Contract Research Organizations (CRO) are now the route by which the majority of companies conduct clinical research. They possess the efficiency and economies of scale to do what is a mundane, process driven task of setting-up, monitoring and processing data associated with a clinical trial on a global basis.  Those models works reasonably well and are now the norm.  Standard Operating Procedures (SOPs) exist for everything a CRO does in what is a heavily regulated process of gathering data for regulatory submissions.

Is this the same for drug discovery? I am not so sure.  Firstly, if you outsource you have to give direction. You have to have a commercial or scientific target, and resources have to be allocated accordingly. Who decides where R&D investment should be spent? Ultimately in any outsourced venture, the company spending the money makes that decision.  So all you are doing is shifting the execution of the task, not the development of the strategy, which is where the innovation needs to take place.

Indeed, if one looks at the clinical trial service model, what has happened is that consolidation of small and medium size CRO’s continues to take place.  Small companies simply lack the resources to get the job done. I am not convinced that small is necessarily best when it comes to drug discovery.

What’s more, Munos, in the recent Science Translational Medicine (STM) commentary on innovation that he wrote with William Chin, appears to argue for a different model than the one he proposes in Forbes.  He states that:

“pharmaceutical companies cannot mitigate risk adequately by pursuing “safe” incremental innovation, instead the industry should reengage in high risk discovery research on a broad scale and only take genuine breakthroughs to the clinic.”

This is easy to say in practice, and may not be a realistic strategy when there is money and sales to be made from me-too and follow-on compounds. How many companies are going to say we are not going to continue with this business model?

According to Munos in Science Translational Medicine (STM) the options open to big pharma are to:

  • Participate more decisively in collaborative networks
  • Form precompetitive consortia and other partnerships to share costs
  • Adopt new research models such as public-private partnerships

To me, there seems to be a disconnect between what Munos says in the Forbes article and what he says in his STM commentary.  If he has a clear vision for the future of pharma innovation, he should at least be consistent.

Where I do agree with Munos is the conclusion of his STM commentary that success starts with breakthrough science. This message was also clearly stated at BIO 2011 by the panel on innovation that included GSK’s Moncef Slaoui.

Pharma R&D $ needs to be spent more wisely. In my opinion there is a role for incremental, as well as breakthrough, innovation. The two are not mutually exclusive.

Is cutting R&D and outsourcing discovery the route to success as Munos suggests in Forbes?  Only time will tell as pharma R&D retools and refocuses for the future.

ResearchBlogging.orgMunos, B., & Chin, W. (2011). How to Revive Breakthrough Innovation in the Pharmaceutical Industry Science Translational Medicine, 3 (89), 89-89 DOI: 10.1126/scitranslmed.3002273

Innovation involves insight that allows you to see around the corners. That’s the perspective according to Andrew Marks, Professor of Physiology & Cellular Biophysics at Columbia University Medical Center, who recently wrote a Commentary on Innovation in Science Translational Medicine.

Entitled “Repaving the Road to Biomedical Innovation Through Academia”, Professor Marks’ commentary captures the reader’s attention in the first sentence:

“The path to biomedical innovation requires a synthesis of seemingly unrelated observations.”

He goes on to say, “innovation requires joining the pieces to solve the puzzle.”

Innovation according to Marks is difficult to define, something I also noticed at BIO 2011 in the industry panel that I attended.

However, like pornography, “we know it when we see it” to paraphrase Justice Potter. Mark gives examples of innovation in the biological sciences: germ theory of disease by Lister, discovery of antibiotics exemplified by Fleming, Watson & Crick’s work on the structure of DNA.

I don’t disagree that these are examples of paradigm shifting scientific discovery fueled in some cases by serendipity. But are they the best examples of innovation in the biological sciences? Has nothing innovative happened in the past 50 years that is worth mentioning?

In his commentary, Marks goes on to outline the reasons he thinks biomedical research is threatened in the current environment. This includes the standard litany of woes expressed by many academics today:

  • increased costs
  • insufficient support
  • limited industry support
  • prolonged postdoctoral training
  • limited opportunities for research careers in academic medicine

Interestingly, however, he suggests that part of the fault for this lies with academia.

Academia and the National Institutes of Health (NIH) have failed to evolve with the times, he writes. They “have been guilty of a lack of innovation” in how they support science.

Today’s challenge according to Marks is the need to balance revolutionary research that is innovative with incremental research necessary to further knowledge.

Marks goes on to say that the NIH is not well equipped to judge innovative groundbreaking research.  Moreover, “the unwritten rule, often said tongue in cheek, is that when applying for NIH funding one should only propose experiments that one has already done and for which one can show convincing preliminary data.”

The solution he proposes is to change the way federal funding of biomedical research takes place. The NIH should divert to industry the costs of clinical trials and establish distinct funding mechanisms for high-risk research. I am not sure I agree with this, as many clinical trials would not be funded by industry and translational research is not just about basic science, but is from bench to bedside.

The solution proposed by Marks also predisposes that you can properly assess and judge innovative research when you see it.  This is not as easy as it seems. As Marks points out:

“NIH likely would not have funded proposals to test the germ-theory, antibiotic-action, or DNA double–helix hypotheses because these projects either would have been deemed too risky (that is, they have a low likelihood of success) or too speculative (lacking in sufficient “preliminary data”) or because the approach would have been criticized as being misguided.”

Instead of looking for new ways to fund basic science, Marks proposes a rework of the way NIH funds research.  Cutting the same cake in a different way is unlikely to solve the fundamental problem: there is simply not enough government funding to go around. In the face of the US budget deficit, it is hard to imagine a significant increase in NIH funding to create new funding opportunities.

Would a more innovative approach be to ask academics to rethink how research is funded in their institutions?  Focusing on the NIH and Federal Government funding is not the optimal solution in my opinion.

Marks is right in that Academia needs to innovate how science is supported. Incremental change of the way NIH funding takes place may fill in some potholes, but will not repave the road to biomedical innovation.

ResearchBlogging.orgMarks, A. (2011). Repaving the Road to Biomedical Innovation Through Academia Science Translational Medicine, 3 (89), 89-89 DOI: 10.1126/scitranslmed.3002223

White House Washington DC BIO 2011 Convention © Pieter DroppertOne of the sessions at BIO 2011 in Washington DC that I hope to make if my travel plans permit, is the Monday afternoon session on “What is the Future for Innovative Medicines in Our Industry’s Pipeline?”

The June issue of Nature Reviews “Drug Discovery” attempts to answer this question by looking back at what happened to the R&D projects involving 28,000 compounds investigated since 1990.

Fabio Pammolli and colleagues analyzed the Pharmaceutical Industry Database (PhID) maintained by the IMT (Institutions, Markets, Technologies) in Lucca, Italy.

In their Drug Discovery article entitled “The productivity crisis in pharmaceutical R&D,” they reach a number of conclusions, some of which are:

  • Output of new drugs has not matched investment in R&D
  • Therapeutic innovation has become more challenging and complex
  • Decline in R&D productivity is associated with investments in R&D areas where risk of failure is high
  • There is no evidence of any R&D productivity differences between United States and Europe.

The authors analyzed R&D investment decisions by looking at the potential pay-off for an R&D project (probability of market launch multiplied by potential market value) and the expected Probability of Success (POS) in reaching the market based on the average success rate of compounds with the same pathology.

What I found interesting in their paper was the fact that many of the therapeutic areas with the highest percentage of R&D projects had the lowest average POS e.g. cancer drugs (antineoplastic and immunomodulating agents) had the lowest POS (1.8%) and the highest share of total projects (21.77% from 1990 to 1999, increasing to 29.77% from 2000-2007).  The 1.8% average probability of success can be contrasted with 4.19% for musculoskeletal system drugs and 6.64% for dermatologicals.

The authors argue that the data shows a shift towards therapeutic markets with a lower POS. What are the reasons for this? Possible explanations include:

  • Orphan drug development incentives: legislation that provides incentives to undertake drug development for rare diseases (orphan drugs) has led to a shift towards these targets, which by definition have smaller markets.
  • Development of drugs for chronic diseases e.g. Alzheimer’s disease: Collectively these have a POS of 6.88% compared to the acute disease average POS of 8.77%.  85.80% of R&D projects from 2000-2007 were within this category.
  • More research targeting lethal diseases such as cancer and infectious disease, which have an average POS of 5.54% compared to non-lethal diseases, average POS of 9.72%.

The authors conclude from this research that:

“R&D investments tend to focus on new therapeutic targets, which are characterized by high uncertainty and difficulty, but lower post-launch competition.”

This article offers some interesting retrospective analysis, but I am concerned that they may have underestimated the market potential for many rare disease areas where market size cannot properly be quantified.

As Novartis showed with imatinib (Gleevec®/Glivec®), it is possible to build a blockbuster out of a very small, rare market (only 4,500 – 5,000 new diagnoses of CML per year in the United States), creating a new market segment and moving the leukemia from a certain death sentence to a chronic disease that can be easily managed with targeted therapy.

The focus of many biotechnology and biopharmaceutical companies on orphan drug development has been shown to be a valid strategy by Genzyme and others.  Proving you can bring a product to market and obtain some revenue is likely to stimulate more company investment rather than less.

In the run up to BIO 2011 several companies have highlighted their orphan drug strategy, including Oklahoma City based Selexys Pharmaceuticals who announced news about SelG1 in Sickle Cell Disease and Lamellar Biomedical from Glasgow with LMS-611 for Cystic Fibrosis.

I am looking forward to learning more at BIO on how industry experts view the future for innovation within the sector.  Also whether the orphan drug strategy that many biotech companies are now following will pay off given the lower probability of success in rare indications.

All in all, the 2011 BIO international convention is set to be an interesting and informative meeting.  Business cards, comfortable shoes and camera/video – I’m ready!

ResearchBlogging.orgPammolli, F., Magazzini, L., & Riccaboni, M. (2011). The productivity crisis in pharmaceutical R&D Nature Reviews Drug Discovery, 10 (6), 428-438 DOI: 10.1038/nrd3405

Today in the plenary session of the 102nd Annual Meeting of the American Association for Cancer Research (AACR), Lynda Chin from Dana-Farber Cancer Institute in Boston provided an excellent overview of the challenges and opportunities of translating insights from cancer genomics into personalized medicine that will benefit patients.

I unequivocally recommend listening to the webcast of the plenary when it is posted on the AACR website.

As Dr Chin stated at the start of her presentation, “cancer is fundamentally a disease of the genome.”  The goal of all cancer research is to make progress with prevention, detection and cure.

In the plenary presentation she highlighted some of the successes that have come from understanding the genome e.g. the knowledge of BRAF mutation in melanoma led to the identification of a target and development of a new drug in 8 years.  In addition to the development of novel therapeutics, genomics research has helped companies reposition drugs and she highlighted crizotinib as an example (move from C-Met to ALK inhibition in NSCLC).

These successes have “motivated researchers” according to Chin.  However, it is transformative new technology such as the next generation of sequencing technology that has heralded “a new era of cancer genomics.”  Massively parallel sequencing enables comprehensive genome characterization.

Not only has innovative new sequencing technology increased the throughput, but it has dramatically decreased the costs.  As Dr Chin noted, some have questioned whether cancer genomics is worth it?  She outlined some of the recent successes, such as BAP1 in ocular melanoma (see my previous post on this) as examples of its value.

Challenges remain such as the management of the vast amount of data that genome sequencing produces.  Data management, processing and storage remain issues, as does the need to develop a reference human genome against which a patient’s tumor profile could be compared.

And even when you find a mutation, the challenge is to separate the “drivers” from the “passengers.” This according to Chin requires a “robust statistical framework”.

Cancer signaling is not linear, but is a highly interconnected and redundant network, so it remains a big task to translate genomics into personalized medicine.  According to Dr Chin using mice as models to bridge the gap between sequencing and man may be the way forward in translating cancer genomics into personalized medicine.

Thanks to Justin Chakma, a student at the University of Toronto, who brought to my attention an interesting article on innovation that he published on Vijay Govindarajan’s Harvard Business Review Blog.

Justin discusses how in emerging markets, venture capitalists (VC) create intentional links between the companies they invest in, compared to the more typical stand-alone investment model we see in Western countries.

By creating an innovation ecosystem, VC’s in emerging markets are able to leverage their investment in multiple companies.  I encourage you to read Justin Chakma’s article, in which he discusses the advantages of this approach in emerging markets.

However, he takes the analysis further and argues that a systems based approach to innovation also has relevance in developed markets.  As an example he states:

“It’s possible for a drug discovery start-up to identify the most relevant patients, and improve clinical trial success and reimbursement rates, if the VC invests in diagnostics or biomarkers at the same time.”

I certainly think that in emerging markets, where there may be a lack of infrastructure and service providers, taking a portfolio or systems based approach can help bring products to market, and capture value for the VC.

However, are venture capitalists in developed countries really interested in creating an ecosystem around their investments?  A VC investing in a biotechnology company has no need to buy a contract research organization for clinical trials, plenty exist nor is there a need to develop the whole system of outsourced service providers necessary to bring a drug to market. I am also not sure that VCs in America are interested in the huge cost of biomarker and diagnostics development for start-ups.

Many VC’s already diversify by investing in a range of companies within a sector.  Is there additional value to them in creating formal links and synergies within this portfolio, turning VC’s into mini-conglomerates?  I think we need to see more data in support of the idea that a systems based approach does in fact speed-up innovation and time to market.

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