landscape of academic and industrial r&d in biologics...

Landscape of Academic and Industrial R&D in Biologics in Cambridge.

Albert Perez-RibaPhD student in Pharmacology, University of Cambridge.BBSRC Doctorate Training Partnership.

Cambridge Cluster of Biopharmaceutical Innovation

Academic ResearchPrivate Research and Drug

Development

Biologic and Physical Sciences Departments

Clinical Medicine Departments

Independent or Associated Institutes

Biologics R&D Companies

Providers of Biologics and Reagents

Technology Providers for Biologics

Structure of the Biopharmaceutical Cluster

Part I: Mapping of Academic Research in the Cambridge Region

Methodology

1. Database of all life-science researchers listed by the university websites

2. Each principal investigator (PI) description of their research

3. Literature search using Pubmed and Web of Knowledge

We wanted to know the following:

How many principal investigators are in total doing life-science research?

How many of them are working on biologics R&D?

What are they doing if not?. What is Cambridge doing research on? Combinations of 2-5 keywords defining each research project

Innovation of Biopharmaceuticals at the University of Cambridge

New protein biologics New non-protein biologics New antibody targets

Clinical trials in Cambridge uni and ARU

Vaccine development

Innovation of Biopharmaceuticals at the University of Cambridge

~5% of total research in University of Cambridge (a total of 778 PIs).

• Computational design of binding.

• New protein scaffolds.• Research in protein

engineering for bio-betters.

• Nanoparticles• Gene therapy• New peptides (stapled or

conjugated)• Stem-cell

• Monoclonal Ab• Re-purposing

• All phases• Medical and Veterinary• Collaboration with industry

• New targets• New storage

5%?? What is Cambridge academia doing?

Why are they not out there making money?

Most of it is basic research with some doing translational work (becoming necessary for funding).

Cambridge is developing basic understanding in multiple crucial areas for the future of biopharmaceutical development.

Innovation of biopharmaceuticals at the University of Cambridge

BSc88%

TSc12%

Biological Sciences

BSc67%

TSc33%

Medical Sciences

BSc97%

TSc3%

Independent institutes

347 PIs 240 PIs 191 PIs

Research Ground at the University of Cambridge

Any research that intends to find a useful application to scientific knowledge for the benefit of society, usually patients. (e.g. drug/vaccine development, diagnostics, clinical trials, med. tech.-related…

Keyword Classification

Molecular Genetics

47%

Genomics43%

Epigenetics10%

25% of Cambridge labs are involved in Genetics

Pathology40%

Infectious Diseases36%

Neuropathology24%

27% in Human Pathologies & Diseases


Just over a 4% of the university doing both.

A 13% (101 PIs) are involved in cancer research.


Cancer research in Cambridge mainly involves:

• Molecular Biology of Cancer

• Genomics and Genetics studies

• Signalling

Case Study: Cambridge Neuroscience Network

Neurophysiology41%

Neuropathology30%

Neuropsychology12%

Nerurology10%

Neuroendocrinology5%

Neuropharmacology2%

22% of Cambridge labs listed are involved in neuroscience.

199 researchers as Cambridge nodes.

Clinical Neurosciences

Psychology

Psychiatry

Brain Science Unit

PDN

Pharmacology

Zoology

LMB

Medicine

Biochemistry

Metabolic Research lab


25 departments or centres of research.

• Clinical neurosciences • Psychiatry• Psychology• Physiology, development

and neuroscience (PDN)


Psychology

Psychiatry

Brain Science Unit

PDN

Pharmacology

Zoology

LMB

Medicine

Biochemistry



Collaborations compiled from public information at the Cambridge Neuroscience Network.

461 Cambridge nodes for 170 PI that facilitated their information to the website.

Average of 2.5 collaborations per person.


Psychology

Psychiatry

Brain Science Unit

PDN

Pharmacology

Zoology

LMB

Medicine

Biochemistry



Blue: UK; 222 edges.Green: International; 348 edges.

There are a total of 895 nodes (PIs) involved in the research that 170 claim to do.

That’s about 5 collaborations in average.


Psychology

Psychiatry

Brain Science Unit

PDN

Pharmacology

Zoology

LMB

Medicine

Biochemistry



A small sample of collaborations was validated through co-publications, nonetheless this could well be a underestimation.

It’s is a good example to see how extended the networking collaborations are in academia.

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Alzheimer Publications from University of Cambridge


The University of Cambridge itself is a large cluster of neuroscience research, and although most of them are not actively developing drugs, the knowledge created is necessary for drug development.


Cambridge is a vibrant academic environment of research innovation.

What about IP production and development of biopharmaceuticals?

Is a 5% enough?? Should it increase?

Greg Winter was a single PI, and the LMB doesn’t have that much translational research.

The strength of the region may be more related to the “XO1 example” than directing basic research into biopharma.

Part II: Mapping of Private Research in the Cambridge Region

Cambridge Region as a Biopharmaceutical Cluster

More than 1500 high-tech companies in the Silicon Fen, employing +50k people

Over 200 health-care and life sciences companies:

• Pharmaceutical R&D

• Biotechnology providers

• Diagnosis technologies

• Services for life sciences companies

• CRO for R&D and clinical trials

• Software for life sciences

Mixture of Cambridge IP from the University and external sources

Biopharmaceutical Innovation in the Cambridge Region

What do we classify as biopharmaceuticals or “biologics”?

Monoclonal Antibodies only?...

What about small peptides? And stapled ones?

Do we count vaccine production and development?

Stem-cells therapies too…?

….and Bi-specifics of course

Technology is clearly expanding and diversifying.

1. Amgen2. AstraZeneca3. Cantab Biopharmaceuticals4. Takeda Cambridge5. Vectura6. Actigen7. Gilead Sciences8. MedImmune9. Isogenica10. Bicycle Therapeutics11. Biosceptre UK12. Cambimune13. Cambivac14. Crescendo Biologics15. Iontas16. ImmBio

17. Kymab18. Recombinant Antibody Technology19. XO1 (J&J)20. Neusentis (Pfizer) 21. Vhsquared22. F-star

1. Arecor2. Innova Biosciences3. Antitope (Abzena)4. Polytherics (Abzena)

1. Lonza Biologics2. Abcam3. Europa BioProducts

R&D Biopharmaceutical Companies Technology providers for Biologics

Biologics providers


• MedImmune• Gilead Sciences• Amgen• Takeda Cambridge• AstraZeneca• Pfizer • GlaxoSmithKline• PPD• Lonza

Large and mighty

Traditional multinational companies are suffering a metamorphosis since the start of the biologics era.


They did not start the cluster, but all felt attracted to it for one reason or another….

…Nonetheless, they power the cluster synergically in multiple ways.

There is still a continued trend of settling large research centres in the Cambridge region, having AZ as the most recent example.

GSK has a strong presence in the Biomedical Campus with its clinical trial unit

PPD and Lonza work in a different dynamics as being a multinational CRO.


• Multinational R&D companies have large pipelines and strong in-house research.

• They tackle multiple areas of research.

• It is difficult to know which of their centres is specialised in what.

To understand their role in the cluster we need to understand in what are they changing. All of them seem to be following the same trend:

• Opening to academic collaborations while reducing in-house basic research

• Pressure to publish their work. New standard of quality appearing.

• Developing a network of academic consultants.

• Spin out their assets in new and much smaller companies

• Favouring a single asset drug development


Opening to academic collaborations.

Joint scheme with the University of Cambridge to fund:• +80 PhD studentships• 8 clinical lectureships

Cambridge – MedImmune PhD scholarships. Up to 6 per year.

Amgen Scholars Cambridge. 20-25 undergraduate studentships per year.

Wellcome Trust and University of Cambridge Clinical PhD programme


Contacting Cambridge academics for consultancy. (Developing of new areas of research)

Collaborations are usually difficult to trace. Most of them are kept quiet because they can become future directions in the research and pipeline of the company.

The University of Cambridge is nonetheless promoting collaboration through a growing administrative force.

Therapeutics consortium. To connect academic and clinical researchers at theUniversity of Cambridge, the Babraham Institute and the Wellcome TrustSanger Institute with pharmaceutical companies Astex Pharmaceuticals,AstraZeneca and GlaxoSmithKline (GSK).


Pressure to publish their work. New standard of quality appearing.

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Pfizer publications count 1970-2012

Total count UK U of Cam

Pfizer 77411 11607 290

AstraZeneca 39242 12168 112

Amgen 29641 1132 37

Top collaborative publishers in the region


Acquiring Cambridge-developed IP promoting a dynamic culture of entrepreneurship and single asset development.

Acquisition of CAT. The very origin of the biocluster.

Acquisition of Domantis. The 2nd generation Greg Winter’s research.

Acquisition of Paradigm Therapeutics.

Other examples: J&J acquires XO1 (single asset), Pfizer brings Neusentis.


• Abcam• Kymab• F-star• Antitope (Abzena)• Crescendo Biologics• Innova Biosciences• Polytherics (Abzena)• Neusentis (Pfizer)• Vectura

Stories of success

Two of them started from Cambridge University IP: • Kymab (Sanger Institute).

• Crescendo (Babraham Institute).

Abcam is also one of the most successful Cambridge Start-ups.


• Development of a new generation of antibody drugs:

Cambridge technology to generate humanized antibodies against difficult targets.Overcoming previous limitations of humanization.

Generation of humanized antibody fragments.

Bispecific antibodies to target and bring targets together.

All three in a stage where several millions have been secured and they can develop pipelines alone or through partnering.


Drug-antibody conjugates and improved pharmacokinetics

• Providers of high quality biologic products and services to industry and academia.

Provider of monoclonal antibodies, assays, cell lines, peptides and proteins.

Immunogenicity, humanization and cell lines for drug discovery

• Technology Providers for Biopharmaceuticals

Antibody labelling and conjugates. Nanoparticles.


Developed over a new delivery technology for respiratory diseases that is developing small molecules and biologics with multiple partners.

A Pfizer company. Mainly specialized in ion transporters and pain, they also have R&D in regenerative medicine with stem cells as therapeutics.

• New technologies


Cambridge IP• Cantab Biopharmaceuticals• Cambimune• Cambivac• Recombinant Antibody Technology• XO1 (J&J)• Vhsquared• Talisman• Bicycle Therapeutics• Iontas

External IP• Actigen• Arecor• Isogenica• Biosceptre UK• ImmBio

New technologies and/or single assets

2/3 originated from Cambridge University Intellectual property.

This shows the potential of the region not only to develop new IP, but also to attract start ups to grow here.


Innovative display technologies for antibodies and other biologics. Providing service screening and research partnerships.

New technologies to assemble mini-chromosomes to be integrated in transgenic mice and produce superior humanized antibodies.

Antibody drug discovery with a superior library and large expertise in target validation.

Development of novel antibodies capable of being stable in the gastrointestinal track.

Novel antibody technologies

VhSquared


New oncology target specific of multiple cancer types and not present in healthy cells. Moving to Phase I.

Single asset company produced to develop ichorcumab, an anti-thrombin antibody. Now property of J&J

Providing technologies to stabilise proteins for better delivery of biologics and vaccines.

New targets from academic and clinic research

New protein engineering technologies


A step forward in peptide drugs by generating a library of double stapled peptides, providing improved stability, specificity and affinity. (The 3rd generation of Greg Winter’s research).

Developing the next generation of anti-infective vaccines

With IP developed at the Stem-Cell institute in Cambridge, Talisman is working on the regenerative medicine with stem cells.

Novel vaccines

New therapeutics


Different roles for different players.

• The cluster didn’t start with big pharma, but now they play a crucial role increasing the dynamism of the community and increasing the research quality.

• Multiple successful examples show how this region is a motor capable of generating successful multi-million and billion companies from good science.

• The new generation of start-ups and small companies shows a new tendency to develop new therapeutic approach and new generations of biologics into the market.

• Good representation of Cambridge IP in early stages, but we also see the attracting effect that brings foreign IP.


Existing technologic

cluster

Proximity to London

Strong Hospital and clinic research

Pool of researchers

CAT

New biopharmaceutical technology is developed

generating expertise.

•New companies come to recruit experience researcher

•Accumulation of researchers and companies

Large pharma buys IP

•Brings multinational players and therefore more money to the cluster


Realization of IP value from University and

policy makers

•Promotion more start-ups and IP development. Helped by having large pharma ready to buy.


People want to settle, VC don’t want to travel far and networks grow.

Origins of the Cambridge Biopharmaceutical Cluster

What now?

The cluster seems to have a critical mass that powers it to keep increasing. Could it be stop?

Does Cambridge still has unique expertise so difficult to find than companies feel attracted to come here? Or is know-how more widespread than 20 years ago?

Is the cluster ready for fluctuations in the market or sudden disinterest in biotech from investors?

How could we control this bubble? (is there one?) Tendency to try more and more risky therapeutics. Can we get the invertors too exited and then….

Future of the Biologics in the Region

Thank you and thanks to

• Nadia Shivji• Tony Jones• And everyone from One Nucleus

• Laura Itzhaki (University of Cambridge, Pharmacology Dep.)

• Jane Dancer• Duncan Cochrane and Lynne Murray• Arvind Hundal• James Legg and Brian McGuinness• Steve Dowd

Oliver Gatty Biophysics Studentship

Acknowledgements

landscape of academic and industrial r&d in biologics...

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