Event - Cyclacel Seeking Return on Investment During Crucial Period

June 19, 2008 Event - Cyclacel seeking return on investment during crucial period

Evaluate Vantage

If ever there was a company facing a critical “inflexion point” in their development, Cyclacel Pharmaceuticals certainly fits the bill, with pivotal data from four phase II trials on its two lead cancer drugs due within the next six months.

With a historic five-year R&D spend of $81m dwarfing its current enterprise value of $4m, and shares recently trading at historic low levels of $2, investors will be praying the clinical data turns out to be positive, enabling the company to start providing some return on its investment.

The spotlight is expected to land first on lead candidate CYC202 (seliciclib), due to report interim phase II data in nasopharyngeal cancer (NPC) during the third quarter, followed by top-line data from the group’s Phase 2b Appraise trial in non-small cell lung cancer (NSCLC).

Seliciclib is a novel CDK inhibitor, a class from which no products have yet reached the market. Cyclacel’s candidate is just behind Sanofi-Aventis’ alvocidib, currently in phase III for chronic lymphocytic leukaemia (CLL), having previously failed in phase II trials for NSCLC, colorectal cancer and mantle cell lymphoma.

CDK Inhibitors in development - EvaluatePharma Pipeline Analysis

2012 Market Generic Pharmacological WW Status Product Company Lead Indications Name Class sales (currrent) ($m)

Leukaemia, Phase III Alvocidib alvocidib Sanofi-Aventis CDK inhibitor 20 chronic lymphocytic (CLL)

Non-small cell Cyclacel lung cancer Phase II CYC202 seliciclib CDK inhibitor 121 Pharmaceuticals (NSCLC); Head & neck cancers

Leukaemia, Bristol-Myers CDK2, CDK7 chronic Phase I SNS-032 - Squibb & CDK9 inhibitor lymphocytic (CLL); Multiple myeloma

Leukaemia, Sunesis CDK2, CDK7 chronic SNS-032 - Pharmaceuticals & CDK9 inhibitor lymphocytic (CLL); Multiple myeloma

General cancer PD-332991 Pfizer CDK4 inhibitor - indications

Onyx General cancer PD-332991 CDK4 inhibitor - Pharmaceuticals indications

General cancer Pre-clinical RGB-286199 GPC Biotech CDK inhibitor - indications

CDK Cell Cycle General cancer Inhibitor GPC Biotech CDK inhibitor - indications Program

Bristol-Myers General cancer RGB-286199 CDK inhibitor - Squibb indications

General cancer Variolin B Zeltia CDK inhibitor - indications

Cyclacel General cancer CYC400 CDK inhibitor - Pharmaceuticals indications

Consensus analyst forecasts expect 2012 sales for seliciclib to be $121m, resulting in a potential net present value of $725m, according to EvaluatePharma’s NPV Analyzer.

The market opportunity and therefore potential peak sales has never been in doubt, more the lack of pivotal efficacy data so far which has contributed the share price slide over the last few years.

The Scottish group’s second most important product is CYC682 (sapacitabine), with phase II data in advanced cutaneous T-cell lymphoma due shortly, followed by phase II data in acute myeloid leukaemia (AML).

Sapacitabine is a pyrimidine analogue, the same class as Eli Lilly’s Gemzar and Roche’s Xeloda, both current blockbuster drugs.

As the data for seliciclib looms closer, investors in the group might be forgiven for dreaming about the impact of positive data, which will almost certainly provide a much needed opening for partnering discussions. But given the limited success so far for this class, with 9 candidates already dropping out of development, any counting of chickens should be firmly advised against.