The story
Founded by David Chiswell and John McCafferty in 1989.1
CAT was founded in 1989 by Dr. David Chiswell OBE and Sir Greg Winter, with major scientific contributions from Dr. John McCafferty and the Medical Research Council (UK) (MRC). Operations began at the MRC laboratories in Cambridge. In May 1990, operations moved to the Daly Research Laboratories at Babraham Institute, Cambridge.
In 1992, CAT moved to Beech House on the Melbourn Science Park to occupy units B1 and B2. In 1993 the company expanded into unit B3, into B4 into 1995, and in 1998 into units B5, B6, B8 and B9. CAT completed the occupation of Beech House by finally occupying B7 by the late 1990s.
CAT listed on the London Stock Exchange in 1997, raising £43 million, and went through a second round of funding in 2000, raising over £90 million.
In 1999, CAT expanded into a second location in Melbourn called Cambridge House. After leaving Melbourn, CAT sold this location on to housing developers in early 2006.
In 2000, after a succession of deals that focussed on harnessing the exploitation of the human genome, CAT's share price peaked at over £50 per share.
Also in 2000, CAT decided to move out of Melbourn to a science park called Granta Park, roughly 10 miles (16 km) away. Of the buildings on the park, the first to be occupied was the Franklin Building followed, in late 2002, by a move to a new corporate headquarters at the Milstein Building.
The Franklin Building, named after Rosalind Franklin, was formally opened in 2001 by David Sainsbury, Baron Sainsbury of Turville. The Milstein Building was named after César Milstein, and had a modular design with separate laboratory (46,000 sq ft) and administration blocks (21,000 sq ft). In the same year, CAT listed on the NASDAQ.
When AstraZeneca acquired CAT in June 2006, plans were announced to occupy a new building on Granta Park, GP15, offering a further 92,000 sq ft (8,500 m2). Refurbishment of this building took approximately 18 months and the building was officially opened, in November 2008, with the name Aaron Klug Building.
Read the full text
Aptein Inc.
On 15 July 1998, CAT completed the acquisition of Aptein Inc. This acquisition "...further strengthened its world leading position in antibody display technology...giving CAT controlling patents in the field of polysome display. Polysome display involves the use of polysomes, a type of molecule responsible for protein synthesis within the human body, to display functional antibody proteins in vitro.". Three years later David Glover, CAT's Chief Medical Officer at the time, summarised the acquisition as one which essentially acquired Aptein's patent estate
"Under the terms of the agreement CAT purchased the issued share capital and outstanding share options and warrants of Aptein for a total consideration of up to $11 million satisfied by the issue of up to 2.366 million CAT shares (an implied CAT share price of 278p.) $6 million of the consideration was satisfied by the issue of 1.290 million CAT shares on closing. The balance of the consideration of up to $5 million will be satisfied by the issue of up to 1.076 million CAT shares after Aptein's European patents have been sustained through opposition or appeal. In accordance with accounting standards the cost of acquiring this new technology has been capitalised and will be written off over the lives of the patents concerned.".
Aptein was founded by Glenn Kawasaki, who is currently, amongst other positions, CEO at Accium BioSciences.
According to an article published in Nature in 2002, that focused on the automation of proteomics,..."Normally, an mRNA molecule passes through the ribosome-like ticker-tape and is released, along with the newly synthesised protein molecule, when a sequence of three bases known as a 'stop codon' is reached. In Aptein's technology, stop codons are eliminated so that the completed antibody and its mRNA remain bound together on the ribosome. The system, which CAT is now optimising, is entirely cell-free and so is more amenable to automation. This should make it possible to construct libraries that are orders of magnitude larger than those created using phage display."
CAT published on their optimisation work with Ribosome Display, including:
The discovery of tralokinumab, a therapeutic antibody against IL-13.
An improved method for eukaryotic ribosome display
A comparison of phage and ribosome display approaches for improving antibody affinity and stability showing the advantages of ribosome display
The use of ribosome display to optimise pharmacology and "developability" of therapeutic proteins
CAT used extensive data sets from ribosome display to patent protect their anti-IL-13 monoclonal antibody, CAT-354, in a world-first of sequence-activity-relationship claims.
Drug Royalty Corporation Inc.
In 1994, CAT signed a royalty deal with Drug Royalty Corporation Inc. (DRC) such that DRC would receive future royalty revenue from CAT's products.
In January 2002, CAT made a share-based offer to buy DRC for £55 million so that it could buy out this royalty obligation. CAT valued DRC at C$3.00 a share, and this offer was initially recommended by the board of directors of DRC. On 8 March 2002 the investment company Inwest made a competing offer valuing DRC at C$3.05 per share. CAT's offer would see DRC shareholders receiving CAT shares whilst Inwest's offer would see the DRC shareholder receiving cash. DRC's board of directors changed their decision and recommended Inwest's offer. After a number of deadline extensions from CAT the offer from Inwest was accepted by the DRC shareholders. Inwest purchased DRC on 2 May 2002, and the company began operating as a private entity that continues operation today as DRI Capital.
As a result of this failure to purchase DRC, CAT's right to buy back royalty interest was triggered at a cost to CAT of C$14 million (£6.2 million) by way of 463,818 CAT shares.
Oxford Glycosciences
On 23 January 2003 CAT made a share-based offer for Oxford Glycosciences (OGS) and at an Extraordinary General Meeting shareholders voted to approve the merger. In March of this year CAT saw a decline in its share price. Discussions regarding the applicability of the royalty offset provisions for HUMIRA with Abbott Laboratories had started, and these had a negative impact on the CAT share price depressing the value of CAT's offer.
On 26 February 2003 the British-based biotechnology group Celltech subsequently made a hostile £101 million cash offer for OGS and began buying OGS shares. Some reported that this activity represented the UK biotechnology industry's first-ever bidding war. Despite this improved offer from Celltech, OGS continued to recommend the CAT offer.
Celltech continued to buy OGS shares and the OGS board pressed CAT to improve the terms of its offer as the Celltech shareholding reached 10.55%. OGS became alarmed that Celltech's share purchase would prompt CAT to walk away because, under takeover rules, it would not be able to forcibly purchase the 10.55 per cent stake Celltech owned. CAT failed to improve the terms of its bid forcing OGS to abandon the agreement.
Celltech continued buying shares and, as their stake reached 25%, so the board of OGS met to reluctantly recommend the Celltech offer. Celltech completed the purchase of OGS in April 2003. Some newspapers reported that the failure of the bid by CAT would means that CAT would have to cut some of its workforce. Celltech was itself purchased by the Belgian drugmaker UCB in mid-2004.
Genencor
On 1 November 2005 CAT announced it was acquiring two anti-CD22 immunotoxin products from Genencor, namely GCR-3888 and GCR-8015. Genencor is the biotechnology division of Danisco and the acquisition meant CAT would hire certain former Genencor key employees to be responsible for the development of the programmes.
GCR-3888 and GCR-8015 were discovered and initially developed by the National Cancer Institute, which is part of the U.S. National Institutes of Health. Genencor licensed the candidates for hematological malignancies and entered into a Cooperative Research and Development Agreement (CRADA) with the NIH, which will now be continued by CAT. Under the original
licence agreement with the NIH, CAT gained the rights to a portfolio of intellectual property associated with the programs and would pay future royalties to the NIH.
CAT intended to file an Investigational New Drug (IND) application for GCR-8015 in various CD22 positive B-cell malignancies, including Non-Hodgkin lymphoma and chronic lymphocytic leukaemia, following a period of manufacturing development which is expected to be complete by the end of 2006 and to support the NCI's ongoing development of GCR-3888 in Hairy cell leukaemia (HCL) and paediatric acute lymphoblastic leukaemia (pALL).
CAT-8015 exhibited a greater affinity for CD22 than its predecessor, CAT-3888 and CAT's language such as "CAT will support the NCI's ongoing development of CAT-3888..." suggested at the time that their focus was on the second generation candidate.
On 16 May 2013, AstraZeneca announced that CAT-8015, now Moxetumumab, has started Phase III clinical trials.
Collaborations
CAT entered into many collaborations with technology and pharmaceutical companies, including:
Searle, 1999 – CAT signed, what was at the time, their biggest deal with Searle, the pharmaceutical arm of Monsanto. In 2000, Pharmacia & Upjohn merged with Monsanto and Searle to create Pharmacia Corporation. In 2003, Pfizer acquired Pharmacia. It is unsure as to whether the deal with Searle generated any clinical candidates.
Human Genome Sciences, 2000. GlaxoSmithKline purchased HGSI in 2012. The deal with Cambridge Antibody Technology generated, amongst others;
An anti-BLyS antibody – registered by HGSI as LymphoStat-B, also known as belimumab, and subsequently branded as Benlysta. On 16 November 2010 HGSI and GlaxoSmithKline announced the vote of the FDA advisory committee to recommend approval of belimumab for systemic lupus erythematosus. On 9 March 2011 the FDA voted 11 to 2 in favour of approving Benlysta "to treat patients with active, autoantibody-positive lupus who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and nonsteroidal anti-inflammatory drugs".
An anthrax therapeutic antibody – registered by HGSI as ABthrax, also known as raxibacumab. At the 2 November 2012 meeting of the Anti-Infective Drugs Advisory Committee to the US Food and Drug Administration (FDA) members "voted 16 to 1 in support of the clinical benefit of raxibacumab for the treatment of inhalational anthrax, with one abstention. In addition, the committee voted 18 – 0 in favour of the risk-benefit profile of raxibacumab".
Two anti-TRAIL receptor antibodies – mapatumumab (HGS-ETR1) and lexatumumab (HGS-ETR2). Early work by CAT and HGS scientists showed that HGS-ETR1 induces cell death in certain tumour types. Following this data, HGS exercised an option to enter into an exclusive development partnership for the antibody.
Genzyme, 2000. CAT held significant strength in the area of TGF beta with two products already – lerdelimumab (CAT-152) and metelimumab (CAT-192). The deal with Genzyme was "a broad strategic alliance to develop and commercialise human monoclonal antibodies directed against TGF-beta." All clinical indications, with the exception of ophthalmic uses, were covered by the agreement.
The deal resulted in fresolimumab (GC1008), a pan-neutralizing IgG4 human antibody directed against all three isoforms of TGF beta, which had the "potential for treating a variety of diseases". In particular Genzyme are currently using fresolimumab in trials involving immunogenic tumours.
The takeover of CAT by AstraZeneca initiated a change of control clause in the 2008 agreement that gives Genzyme the right to buy out rights to a jointly developed experimental lung drug.
In February 2011, Sanofi-Aventis purchased Genzyme for approximately US$20bn.
Immunex Corp, 2000. CAT's proprietary antibody phage display library for the discovery, development and potential commercialisation of human monoclonal antibodies was licensed to Immunex, in return for a licence fee. This deal was expanded in May 2001 where CAT shared more of the risk of drug development – a so-called "profit-sharing" deal. In 2002 Immunex was acquired by Amgen and in December 2003 CAT entered into a new, restructured agreement with Amgen, reportedly focussing in skin disease. It was also reported that, under the terms of the agreement, Amgen had taken responsibility for the further development and marketing of the therapeutic antibody candidates isolated by CAT against two targets on which the parties agreed to collaborate and would bear all the associated costs. In return, CAT received from Amgen an initial fee and potential milestone payments and royalties on future sales. As of February 2004, one candidate had been delivered by CAT to Amgen. A second candidate was the subject of a continuing research program funded by Amgen and conducted by CAT and was to be delivered to Amgen in due course.
Amgen acquired the transgenic mouse company Abgenix meaning that they had access to two different methods of human monoclonal antibody production. As of July 2009, it is not known from which technology any of their monoclonal antibody products in clinical trials have been derived.
AMRAD, 2001. AMRAD subsequently changed its name to Zenyth Therapeutics and, in mid-2006, Zenyth was acquired by CSL Limited. CAT and AMRAD had gone 50:50 with the original deal over the development of an anti-GMCSF-R antibody, which became CAM-3001. After all this corporate manoeuvring, "CSL decided to license its 50% share in the project to MedImmune...MedImmune commenced Phase I clinical trials in December 2007".
From Wikipedia’s article on Cambridge Antibody Technology, shared under CC BY-SA 4.0.4