Cyclacel Pharmaceuticals CEO Speaks About His Company

by: The Wall Street Transcript

On April 16, The Wall Street Transcript interviewed Spiro Rombotis, President, Chief Executive Officer and a Director of Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC). Key excerpts follow:

TWST: We'd like to begin with a brief historical sketch of Cyclacel and a picture of the things you are doing at the present time.

Mr. Rombotis: Cyclacel is about 10 years old. It was spun out of the University of Dundee, Scotland, by Professor Sir David Lane, who is famous for discovering an important tumor suppressor mechanism that begins with the p53 gene. The p53 gene was featured as the cover story in Newsweek a few years later. It has become a hallmark of our understanding of cancer in terms of the modern biology of the cell cycle as about two-thirds of all humans with cancer have either a mutation or dysfunction of p53. After diligent study, scientists, including some at Cyclacel, have discovered a number of key enzymes that are regulated by p53 and related cell cycle genes that are possibly accountable for healthy human beings controlling cancer from occurring and not contracting the disease.

The purpose of our company is to exploit these insights and discover drugs that mimic the function of tumor suppressor genes. Our understanding of the biology of the cell cycle enables us to discover new compounds that can be given to people with cancer, who can hopefully control their disease and live a normal lifespan like the experience that diabetic patients have today. At the same time, we aim to design treatments for cancer that have manageable side effects unlike the experience of patients treated with today's toxic chemotherapies.

TWST: Would this apply to a number of different kinds of cancer?

Mr. Rombotis: Yes, these are very broad biological mechanisms applying in many different types of cancer. In fact, the 2001 Nobel Prize for Medicine cites the discovery of enzymes called CDKs, or cyclin-dependent kinases, that are targeted by p53 as part of the cellular machinery that controls cancer in healthy human beings. Obviously in people with cancer, this machinery is not operative. Our goal at Cyclacel is to generate chemical molecules taken by mouth called CDK inhibitors that can target the same Nobel Prize enzymes or aurora kinase inhibitors that target similar cell cycle mechanisms.

TWST: What stage are you at now in your work?

Mr. Rombotis: We have three drugs in clinical development. The most advanced is a CDK inhibitor called seliciclib. It is in Phase II trials in non-small cell lung cancer, the most significant variant of lung cancer known today. It is soon going to enter Phase II development for a different cancer called nasopharyngeal or NPC that is tumor of the nose and pharynx. Our second drug called sapacitabine is just now entering Phase II development in both solid tumors and hematologic cancers. Sapacitabine belongs to the nucleoside family of anti-cancer drugs, several of which are on the market. But it has some unusual features. Unlike most nucleoside analogs it is available by mouth. It also works by a different mechanism than the best known nucleoside analog, a drug called gemcitabine or Gemzar, which is generating annual sales of about $1.3 billion. This different mechanism may explain why sapacitabine is showing signals of activity in Phase I trials in cancers for which gemcitabine has not been shown to be active. Our third drug, which is about to enter Phase I trials in humans, is still called by its code, which is CYC116. That is the compound that addresses an important cell cycle target called aurora kinase, which was discovered by a Cyclacel scientist, Professor David Glover. At the same time it targets a mechanism also targeted by some recently approved, anti-cancer drugs -called Avastin and Nexavar. That target is called VEGFR2, which stands for vascular endothelial growth factor receptor 2, an important target in modern oncology. VEGFR2 inhibitors do not target the cell cycle, but rather restrict blood flow around tumor vessels, a process angiogenesis inhibition, so that the tumor stops growing. CYC116 is unique to our knowledge as it simultaneously targets a cell cycle mechanism and an angiogenesis mechanism.

TWST: What would be the two or three best reasons for the long-term investor to look very closely at Cyclacel?

Mr. Rombotis: One, we are offering investors a pure play in multiple targeted drugs arising out of cell cycle biology. People accept that this is an important area because many of the approved cancer drugs of our day, from platinums to taxanes to nucleosides, work on the cell cycle. So it seems fair to say that this is not about new unvalidated biology, even if our targets and drug mechanisms are novel. Our challenge is to develop drugs that will hopefully emulate how existing drugs work, but with a lot less toxicity and better efficacy. Two, we are offering an interesting mid-stage pipeline with Phase II outcomes for both seliciclib and sapacitabine in 12 to 18 months from now. Then there is the chance of success of the third drug, CYC116, that addresses an important, un-validated target - aurora kinase - but also VEGFR2, a validated target generating hundreds of millions of dollars from recently approved anti-cancer drugs like Avastin and Nexavar. Further, Cyclacel's multiple drugs with multiple indications suggest a balanced risk drug portfolio for investors wishing to benefit from this area of biology. The third reason to invest in Cyclacel is relative value as we compare favorably to peer companies at our stage with an enterprise value in the range of $80 to $100 million.