The two lead compounds are PaTrin-2 and AQ4N. PaTrin-2 is an inhibitor of the DNA repair
enzyme AGT, and appears to enhance the efficacy of certain types of cytotoxics in treating
cancer. Two Phase II trials will be conducted using PaTrin-2 in metastatic melanoma and
colorectal cancer. AQ4N is a potent killer of cells for use in cancer therapy but is only activated
in the hypoxic cells within solid tumours. These cells are not killed by radiotherapy or the
chemotherapy regimens used today and are recognised as a major cause of resistance. AQ4N
is currently in Phase I clinical trials.
KuDOS also has earlier drug discovery programs and has discovered several potent, highly
selective, small molecule inhibitors of the DNA repair enzymes ATM, DNA-PK and PARP.
KuDOS expects to be able to select lead candidate compounds from these programs to enter
pre-clinical development in 2003.
In October 2001 a follow-on investment of £0.3m was made in the German company, Axxima
Pharmaceuticals, as part of a £21m financing round. This increased IBT's total investment in
Axxima to £1.4m. Axxima is an infectious disease, drug discovery company focused on small
molecule compounds to block critical signal transduction pathways required by pathogens for
survival. Axxima is searching for drug candidates in the areas of HIV, Hepatitis B and C,
influenza, human cytomegalovirus, and tuberculosis.
In August 2001, IBT made an investment of £1.8m in Eyetech Pharmaceuticals and a
commitment to invest a further £1.6m in August 2002, subject to milestones. Eyetech's lead
product, Macugen, is designed to inhibit the biological pathway that causes vision loss in age-
related macular degeneration (AMD) and diabetic macular edema (DME), two of the leading
causes of blindness in the adult population. Enrollment was completed in the pivotal Phase II/III
trials for AMD in August 2002, enrolling 1,196 patients at 117 sites worldwide. This triggered the
second installment of the financing agreed in August 2001. Eyetech is also conducting Phase II
trials with Macugen for DME. Alternative delivery systems for Macugen are under development
as it is currently administered via injection into the eye. Eyetech has also in-licensed other
promising compounds for treating diseases of the back-of-the-eye.
Also in August 2001, IBT invested £1.3m in the Swedish company Affibody and committed to
invest a further £1.4m a year later. This second tranche was invested in September 2002,
following the end of the reporting period
Affibody uses cutting-edge combinatorial protein
technology to create Affibodies. These are small, novel, robust ligands, which can be
engineered to bind to any desired protein. Affibodies mimic monoclonal antibodies in many
ways and their unique properties make them a preferred choice for a number of diagnostic,
proteomic and therapeutic applications. Since the initial investment was made there have been
significant advances in the production and characterisation of Affibodies and the library of these
ligands has increased in size to around three billion variants. The strategic partnership with
Amersham Biosciences in the area of separations has been broadened and lengthened. In
addition Dr Hakan Mogren, the former CEO of Astra has joined as Chairman. Preclinical
experiments are ongoing to test the possibility of using Affibodies as therapeutics; much of this
data should be gathered by the end of the year.
As outlined in the interim report, two of the unquoted US-based companies in the portfolio were
sold to trade buyers during the year, however the returns on both investments were
disappointing. Elan announced that Delsys Pharmaceuticals would merge with one of its
subsidiaries, realising £1.2m for IBT (cost £6.3m). This resulted in a write-up for IBT of £1.2m
during the period under review as the holding had previously been written down to nil.