1. Pioneering patient-centred, side-effect free cancer treatments

2. Executive Summary  Transcription factors control the function of all genes and are often found in excess in cancer cells. Transcriptogen (TSG) is developing a portfolio of drugs based on the inhibition of transcription factors (TF) as a treatment for cancer.  TSG has developed a TF-based “Drug Discovery Engine” and has a pipeline of early and late-stage inhibitors. Our lead drug (TSG1301) has significant efficacy with remarkably low toxicity, and has a long patent life (~ 20 years).  The initial focus is on pancreatic and breast cancer.  Funding ~£5.2m is required to complete phase IIa clinical studies of TSG1301,further development of the next candidate (TSG1500 family), and the generation of new lead inhibitors for other transcription factors (e.g., AP1).

3. TSG molecules selectively inhibit gene expression by interacting with (and thus blocking) the binding sites of key transcription factors (TFs):  Present focus in oncology  Approach has potential in other therapeutic areas (e.g., inflammation)

4.  Energy minimised molecular model showing inhibition of interaction of NFĸB (red) with its cognate DNA sequence (grey) by KMR-28-39 (blue).  The imidazole ring of KMR-28-39 is shown interacting with Lysine 145 of the NF-  B protein (highlighted in yellow), thus sterically hindering approach of the protein to its DNA binding site. Structure and Mechanism of Action of TSG1301 TSG1301

5. Key Advantages of TSG Portfolio TSG agents are active at very low concentrations, and have low toxicity. Thus they are likely to dramatically reduce side-effects in patients compared to current chemotherapy agents. TSG agents offer a “Personalised Medicine” approach to cancer therapy. Biopsies will be possible to determine which TFs are over- expressed in individual tumours so that the most appropriate drug can be selected, thus personalising the therapy. Ability to sensitise drug-resistant cancer cells. TSG agents have the potential to sensitise cancer cells to other types of chemotherapy. For example TFs such as EGR, NFAT and OCT-4 are all associated with chemotherapy resistance, so TSG’s agents can potentially down-regulate these TFs, thus allowing combination as well as single-agent use. Orally active formulations of TSG anticancer agents are being developed.

6. Selective Cytotoxicity of TSG1301 CompoundIC 50 (nanomolar) A431A549Mia Paca 2MCF7MDAMB-231WI38 TSG13000.00560.0560.00130.000020.000065473.8 TSG13010.0180.0340.00210.000020.00018129.2 Results from cellular screening: Molecules are exquisitely cytotoxic in cancer cells (e.g., Femtomolar in breast tumour lines MCF7 and MDAMB-231) but over 7 million times less toxic in normal healthy cells (e.g., the non-cancer skin cell line WI38).

7. Low Toxicity of TSG1301 in Mice  MTD (Maximum Tolerated Dose) determination for TSG1300 (KMR-28-35) and TSG1301 (KMR-28-39) in mice.  A small but significant weight loss was observed for TSG1300 at the 400 µg/kg/day dose level, but not for TSG1301 at the 300 µg/kg/day level.

8. Antitumour Activity of TSG1301 (KMR-28-39) in Human Tumour Xenograft Mouse Models of Breast (ER-Negative MDA MB 231) and Pancreatic (MIA PaCa-2) Cancer  250µg/Kg or 300µg/Kg Daily x 5 for 3 weeks, and then daily x 2 in week 4.  Dosing started when tumours reached approximately 0.06cm 3 (~3 weeks post implantation).

9. The Team  Christopher Keightley, Chairman. Chris is presently the MD of Cambridge Research BioVentures Ltd LLC, a life science investor, and subsidiary of RCT. Formerly he was Life Sciences Director at Cambridge Research and Innovation Ltd (CRIL).  Richard J. Turner, Chief Executive Officer. Richard co-founded Transcriptogen in 2013, and has provided seed funding. He is an economist and qualified corporate financier.  David E. Thurston, Chief Scientific Officer. David is presently Professor of Drug Discovery in the Institute of Pharmaceutical Sciences (IPS) at Kings College London. In 2000 he co- founded the oncology biotech company Spirogen Ltd.  Khondaker Miraz Rahman, Head of Medicinal Chemistry. Miraz joined the CRUK Protein-Protein Interaction Research Group in 2008, and became a CRUK Research Fellow in 2009.  Paul Jackson, Head of Molecular Modeling and Computational Chemistry  Sheraz Gul, Head of Screening. He is presently Vice President and Head of Biology at European ScreeningPort GmbH (Hamburg, Germany)

10. Conclusion Patented lead drug showing remarkable cytotoxicy with low side effects Pipeline of drugs from discovery platform in various stages of development Highly experienced management team Commercial interest in lead drug Support from Kings College, Astra Zeneca and Deepbridge Capital

11. Contact Details Richard J Turner Paragon House Lyncombe Vale Road Bath BA24LS Rjt@catvp.com 01225 331498 WWW.Transcriptogen.com 07879 423828