Cambridge Antibody Technology

Cambridge Antibody Technology Group Plc, (commonly referred to as CAT) was a biotechnology company headquartered in Cambridge, England. Its core focus was on antibody therapeutics, primarily using Phage Display and Ribosome Display technology.

Phage Display Technology was used by CAT to create adalimumab, the first fully human antibody blockbuster drug. Humira, the brand name of adalimumab, is an anti-TNF antibody discovered by CAT as D2E7, then developed in the clinic and marketed by Abbvie, formerly Abbott Laboratories. CAT was also behind belimumab, the anti-BlyS antibody drug marketed as Benlysta and the first new approved drug for systemic lupus in more than 50 years. In 2018, the Nobel Prize organisation awarded one quarter of the Nobel Prize in Chemistry to a founding member of CAT, Sir Greg Winter FRS "for the phage display of peptides and antibodies".

Founded in 1989, CAT was acquired by AstraZeneca for £702m in 2006. AstraZeneca subsequently acquired MedImmune LLC, which it combined with CAT to form a global biologics R&D division called MedImmune. CAT was often described as the 'jewel in the crown' of the British biotechnology industry and during the latter years of its existence was the subject of frequent acquisition speculation.

History 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 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 . Refurbishment of this building took approximately 18 months and the building was officially opened, in November 2008, with the name Aaron Klug Building.

Acquisitions

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.".http://www.cambridgeantibody.com/__data/assets/pdf_file/5246/catannualreport1998.pdf| page 29 of the CAT Annual Report 1998

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.http://www.cambridgeantibody.com/__data/assets/pdf_file/5248/interim_report_2002.pdf| page 5 of CAT's 2002 Interim Report

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.page 4 of CAT's 2003 Interim Report

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".