A Canadian Technology Success Story Cancer Therapy: From Concept to Commonplace

Head Table Guests

Anne Libby, Owner, Libby's Fine Art and Director, The Empire Club of Canada; Reverend Dr. John Niles, Victoria Park United Church; Genevieve Poulin, Biotech Analyst, Banque Nationale; Dr. Richard Beliveau, Director of the Molecular Oncology Laboratory, The Cancer Research Centre, Hospital de Sainte-Justine, Montreal; Dr. Daniel Sauder, Professor and Chief of Dermatology, University of Toronto, Sunnybrook and Women's College Health Science Centre; William G. Whittaker, Q.C., Partner, Lette Whittaker and Honorary Director, The Empire Club of Canada; The Hon. Murray Elston, President, Canada's Research-Based Pharmaceutical Companies and Former Ontario Minister of Health; Pierre Lassonde, President and Co-Chief Executive Officer, Franco-Nevada Mining Corporation Limited; Marcel Aubut, Senior Partner, Heenan Blaikie Aubut; and Dr. William Evans, Vice-President, Cancer Care Ontario.

Introduction by Catherine Steele

It is my privilege to welcome our guest speaker, Dr. Eric Dupont. Today in Canada, one in three Canadians face a lifetime chance of being diagnosed with cancer. Ten years from now, the National Cancer Institute predicts there will be twice as many Canadians living with cancer.

Treating cancer is a challenge, but advances are being made. Advances such as MAB gene therapy and those being made by our guest today.

AEterna Laboratories is a Canadian company working to develop a breakthrough therapy in the battle against cancer. Our guest today, Dr. Eric Dupont is one of the inventors of the patents covering the angiogenesis inhibitor compound, Neovastat, being developed by AEterna.

Anti-angiogenesis is a new biological approach to cancer treatment. It works by choking off the blood supply that feeds tumour cells so the cells die and can't spread through the body.

AEterna is promoting this approach to cancer therapy using a substance found in shark cartilage with the goal of finding a treatment for the disease. The company is one of the front runners in an international race to win marketing approval for an angiogenesis blocker.

AEterna's treatment, Neovastat is being investigated in three major areas--cancer treatment, dermatology and ophthalmology. It is estimated that more than 180 million people in North America and Europe could benefit from this product.

Dr. Dupont founded AEterna Laboratories in 1991 while completing his Ph.D. in physiology-endocrinology. He has also completed post-doctoral studies in neuro-endocrinology. He is the author or co-author of over 50 scientific publications and lectures and has received numerous awards of excellence for his work. For example, he was the recipient of the 20th century Award for Achievement from Cambridge, recognised in 1996 as one of the ""Top 40 under 40"" in Canada and AEterna has been awarded Company of the Year in Sainte-Foy.

Ladies and gentlemen, please welcome Dr. Eric Dupont to The Empire Club of Canada.

Eric Dupont

Thank you Ms. Steele and good afternoon ladies and gentlemen.

It is an honour for me to speak today before The Empire Club of Canada, one of our country's most prestigious forums. As you heard in that very kind introduction, I am both a scientist and a businessman, and I am here today representing our team at AEterna Laboratories.

AEterna is a Quebec-based biopharmaceutical company with a single guiding mission: to become an international biotech focused on cancer.

However, if you were to ask me what actually inspires the work we do, I would respond with a single word: hope.

Hope is what I want to talk about today. I want to talk about the progress we've made in cancer therapy, and about our conviction that Canadian research achievements will bring about increasingly successful cancer treatments.

I realise that hope is not a word we easily associate with cancer. In fact, cancer more often evokes fear. It is a very serious, and too often deadly disease, and it touches us all. The truth is, virtually every Canadian will experience cancer, either personally, or through a family member or friend.

This year, nearly 132,000 people in Canada will be diagnosed with cancer. Tragically, approximately 65,000 people will die of the disease.

That is the bad news. But there is truly reason for hope. Scientists and researchers are fighting back, and over the last 20 years we have made tremendous progress. Today, we have a significantly more detailed understanding of cancer in its many forms. Improved screening and early detection have enhanced our treatment programmes. Educational campaigns have contributed to changes in lifestyle and to the improvement of our general health. And the scientific community has been working hard to develop new and diversified therapies. We are starting to see some positive outcomes resulting from these efforts.

Indeed, recent studies indicate rates of decline for most types of cancer. According to the National Cancer Institute of Canada, the mortality rate for Hodgkin's disease, for example, has declined at an annual rate of 5 per cent since 1988.

However, these advances come at a cost. Hundreds of millions of dollars are invested every year in cancer research around the world. In Canada, both levels of government have made cancer research a top priority by financing research laboratories and paying for novel therapies offered by the pharmaceutical industry. Locally, the Canadian Cancer Society in Ontario contributed more than $25 million to cancer research this year.

From an operational point of view, Cancer Care Ontario, headed by Dr. William Evans sitting at our head table, is providing budgets to hospitals and oncology clinics. This organisation is also responsible for the challenging tasks of defining clinical guidelines and assessing the value of innovative therapies for reimbursement purposes.

In the larger scheme of things, however, these R&D expenditures are still relatively low, particularly when we consider both the human suffering cancer generates, and its cost to society.

The National Institutes of Health estimate that annual operative costs for cancer in the United States exceed $107 billion, so there is a pressing need to invest even more in prevention, early diagnosis, treatment, and a cure.

The discoveries of the last 20 years have set the stage for a new era in cancer treatment. In the race to develop new treatments, Canada is among the world leaders, so we have reason to be proud as well as hopeful.

At AEterna, we firmly believe that many of our best hopes for improved cancer therapies lie with biotechnology. Once again, we can be proud that some of the best biotech talent in the world is in Canada. We are leaders. In fact, the Canadian biotech sector now ranks second only to the U.S. in terms of size.

This achievement reflects the hard work of people with vision. We can trace its beginnings back to 1983, when the federal government implemented a national strategy on biotechnology, and the provinces began offering generous R&D incentives.

I realise how the entire biotechnology field has not always resulted in success stories. We have indeed heard stories of start-up companies that failed, or potential treatments that never delivered what they promised.

But I also know something about the possibilities of our research. You see, this area of endeavour has always been close to my heart. In the 80s, my uncle, Dr. Andre Dupont, developed with his colleagues an anti-hormonal treatment for prostate cancer which is still being administered today.

So let me repeat: our research into a new cancer treatment is inspired by hope-hope for improving the quality of life of those afflicted, and hope for an eventual cure.

As I mentioned, our company, AEterna, is based in Quebec City. But as we embark upon the final clinical trials for the cancer treatment we have developed, our influence reaches across the world. This treatment is called Neovastat, and we believe this drug may provide a breakthrough in cancer therapy, and help to usher in a new age of cancer treatment.

Before I tell you about the progress we have made, I should tell you what we are up against.

As you know, cancer is actually a group of diseases. It has been with our species forever; evidence of the disease has even been found in the remains of Egyptian mummies. Over the past 50 years it has become predominant, at least in part because our lifespans have increased so dramatically.

Cancer is characterised by the uncontrolled growth of abnormal cells, which leads to the development of a tumour. These tumours can take over an organ or other part of the body. If they are malignant, tumours can spread through a process called metastasis. If the spread is not controlled, it can result in death.

To date, cancer treatment has generally centred on surgery, radiation, and chemotherapy. In many cases, particularly when the cancer has been detected early, these treatments can be effective. However, the consequences of treatment can often be traumatic and debilitating.

Biotechnical or biopharmaceutical treatments offer a new approach. They aim to supplement traditional therapies, and in some cases, to replace them. Many biopharmaceutical treatments hold out the promise of far less discomfort for the patient, and significantly reduced side effects.

Biotech research in cancer therapy falls into several categories including antibodies, vaccines, gene therapy, and anti-angiogenesis--the area that AEterna is particularly excited about.

Let me explain each of them briefly:

• Bioengineered antibodies when injected into the blood stream, seek out diseased cells, attach to them, and then send out a signal to the immune system to destroy the defect.
• Vaccines are intended to teach our immune systems how to fight a cancer that has already established itself.
• Gene therapy is another interesting area. The goal of gene therapy is to identify and isolate the root cause of cancer-those genes that cause tumour growth or that inhibit our natural defences.

This year marked the completion of the human genome. Now we must determine what role individual genes play in specific diseases.

Which brings me to anti-angiogenesis. A few words of explanation are in order.

Researchers believe that 90 per cent of all cancer cases are dependent on something called angiogenesis. This is a molecular process that involves the generation of a path of blood vessels. The human body constantly generates new blood vessels: as a foetus is formed, for example, or as a healthy body grows, or as the body heals itself after an injury. In these cases, angiogenesis is a normal physiological process.

However, the abnormal growth of blood vessels--pathological angiogenesis--is implicated in the development of more than 20 different diseases.

In the case of cancer, angiogenesis is critical to the development of tumours. A tumour is a living thing. And like all living things it needs to be nourished to survive and grow. It does so by forming new blood vessels around it.

Anti-angiogenesis aims to defeat this process. The underlying principle behind anti-angiogenesis is that the development of these blood vessels may be slowed or halted entirely. If the supply of nutrients that reach a tumour through the blood vessels is cut off, then the tumour is starved, and is unable to develop or spread. It may even shrink. In short, angiogenesis blockers cut off the tumour's umbilical cord, its very support system.

Over the past decade, our research has shown us that there are only two types of cells that do not allow the growth of blood vessels-those that are found within cartilage and the retina of the eye. At AEterna, we have successfully isolated the active molecules that prevent the formation of blood vessels in cartilage.

From this we have developed Neovastat--an oral, biologically active treatment that can interrupt vascular growth to solid tumours. Neovastat contains the molecular key that locks the door to blood vessels.

The concept has an elegant simplicity that I can admire as a scientist. Turning the concept into a workable and safe treatment has been a challenging process for us from both a scientific and business point of view. But the rewards of this success are truly exciting. And they give us genuine cause for hope.

AEterna is not alone in pursuing anti-angiogenesis. Nearly 200 companies are conducting research into angiogenesis inhibitors, with nearly 80 per cent of the work focused on treatments for cancer.

I am proud to say that AEterna is leading the field. We are a front runner in clinical trials and we expect to be among the first to offer an anti-angiogenesis treatment. This means that here we are with a Canadian product that has an excellent chance of opening up a new class of drug for the treatment of cancer throughout the world. This would be a thoroughly Canadian success story. Let's see how we got there.

Between 1992 and 2002, AEterna will have invested more than $100 million in research and therapy development. In a very short time, we have grown from a five-person operation, to a world-class biotech company employing more than 150 people.

From the start, our goal has been to combine scientific leadership with a disciplined and highly strategic approach to developing a commercially viable cancer therapy. It is here that science and commerce really meet.

AEterna financed much of its early research through funds generated by its commercial division, which became Atrium Biotechnologies Inc. this past January.

We have also been fortunate enough to secure the trust of the capital markets. AEterna has been traded on the Toronto Stock Exchange since 1995 and was added to the TSE 300 Composite Index last June. It was also listed on NASDAQ this year.

Additionally, governmental agencies have made significant investments in our research. The National Cancer Institute in the United States has contributed $5 million towards our Phase III clinical trial in lung cancer. And the Government of Canada, through its Technology

Partnerships Program, offered us a substantial vote of confidence in the form of a $30-million grant for the development of Neovastat.

After nearly a decade of hard work, and the support of both capital markets and governmental agencies, AEterna is now very well positioned.

I am particularly optimistic because this year AEterna received the go-ahead from the Government of Canada Health Protection Branch and the Food and Drug Administration in the United States to proceed with two pivotal Phase III trials for kidney and lung cancer.

These clinical trials represent the last step before Neovastat may be commercialised.

We have chosen to focus on progressive renal cell cancer for very specific reasons. There are 34,000 new cases of this disease diagnosed every year in North America, and at present the five-year survival rate is less than 10 per cent. The therapies that are currently available are effective in fewer than 20 per cent of all cases and often produce serious side effects.

Neovastat has already been shown not to produce these debilitating side effects, which is critical to a patient's quality of life. Success in this trial will allow us to seek quick approval from the various regulatory agencies to bring Neovastat to market. We are confident that Neovastat will perform well in these final trials, and that we will be able to begin offering the drug to patients as soon as 2003.

However, with the successful completion of these trials, our work is far from over. Indeed, we have sought approval to begin a clinical trial of Neovastat in patients with multiple myeloma, a form of bone marrow cancer.

The Phase II pivotal trial is also designed to obtain accelerated approval of the drug.

So what lies ahead for us?

In the pharmaceutical sector, four factors contribute to a company's international competitiveness: 1) excellent medical researchers; 2) a timely drug approval process; 3) international standards of patent protection; and 4) open patient access to new medicines.

We believe AEterna has thoroughly met all these conditions. We have the support of some of the best medical researchers in Canada and throughout the world. And we are confident that AEterna especially in the Canadian environment, will benefit from the last three pharmacopolitical factors.

In other words, I am inviting our Canadian decision makers to be part of our success story by recognising it as a breakthrough therapy and therefore allowing speedy approval to ensure quicker availability for the patients.

From a commercial standpoint, Neovastat will be marketed and distributed through a network of innovative and well-established pharmaceutical firms. And in the coming year, we intend to step up efforts to increase our product pipeline by undertaking strategic acquisitions of smaller biotech companies who already have treatments in the latter stages of clinical testing.

At AEterna we have devoted all our energies and skills to developing biopharmaceutical treatments that will enhance the quality of life for human beings. Today, we are very close to ushering in a new age of cancer treatment.

I am convinced that science will find better and safer treatments for cancer. In just a few years, we have made enormous advances. We are increasing our understanding of the various types of cancer, and we are devising better methods of identifying these cancers before they become life-threatening.

And we are coming ever-closer to developing treatments that will substantially improve patients' quality of life. Little by little, we are alleviating suffering and fear.

At AEterna, hope is firmly rooted to rigorous scientific principles. And I profoundly believe that the concerted efforts of our scientific and business communities will make it possible to transform cancer from a lethal to a chronic disease. Success is very much within our reach. Thank you.

The appreciation of the meeting was expressed by William G. Whittaker, Q.C., Partner, Lette Whittaker and Honorary Director, The Empire Club of Canada.