June 1, 2010
As President and COO of Helix BioPharma (TSX,FSE:HBP; OTCQX:HXBPF), John Docherty has been on both sides of the company’s lead topical product. Early on, he ran Helix’s PharmaDerm Laboratories subsidiary, where the topical technology known as Biphasix was developed. Then, he was one of the negotiators of a license from Schering-Plough for its interferon compound. From Helix’s perspective, the goal of the deal was to gain access to a drug compound that appeared to be a very promising candidate for its Biphasix delivery technology. The deal accomplished that objective. In this exclusive interview with BioTuesday.ca, Mr. Docherty elaborates on the company’s development program, including a potential new cancer therapeutic.Let’s begin with a brief historical sketch of Helix.
We were founded in 1995 through an amalgamation of a generic drug distribution company and a diagnostic company. We still maintain the product distribution arm under the name of Rivax Pharma, but since 2000, the real thrust of the company has been oncology. Besides the TSX, we have a listing on the Frankfurt Stock Exchange because a large proportion of our investors are European. We’ve also obtained an OTC listing and an SEC registration, with the goal of expanding our profile in the U.S.How would you describe your business strategy?
We’re developing products to address serious unmet medical needs. That’s important these days because there’s so much competition and it’s critical to be perceived as having a chance to be first in class. With our acquisition of PharmaDerm, we had technology to deliver large molecular weight proteins into the skin. So we decided to find a commercially viable therapeutic to put into this technology.How did your first therapeutic candidate come together?
We decided that a topical interferon therapy would be a superior dosage form for treating ano-genital warts (AGW) caused by human papilloma virus (HPV) infections. So we approached Schering-Plough, which is now a unit of Merck (NYSE:MRK). It had a widely marketed interferon therapeutic called Intron A, which is a potent anti-viral injectable but has significant side effect issues when administered systemically. One of Intron A’s indications is AGW. So we combined their interferon product with our Biphasix technology into a cream as a potentially superior means of delivering interferon for skin diseases. Schering has a worldwide license option for our topical interferon alpha-2b product and under terms of the option, it has the right to become the worldwide marketing partner for the product during a specified period of time after the completion of Phase 3 trials.
We have two indications we’re pursuing under our agreement with Schering: AGW and cervical dysplasia, which is a precursor to the development of cervical cancer and where we think our topical product has the greatest potential. Cervical dysplasia and AGW are variants of HPV and would benefit from localized delivery of a therapeutic. So combining Schering’s interferon with our Biphasix looked like a perfect fit. When you look at cervical cancer, you see a pre-existing infection with HPV that can cause women to develop lesions of the cervical tissue, either high-grade or low-grade lesions. And there’s no pharmaceutical therapy in this space.
Beyond the HPV-induced diseases of cervical dysplasia and AGW, we believe that our topical interferon alpha-2b product could be applied therapeutically to potentially a host of other dermatological disease states including, for instance, basal cell carcinomas and actinic keratosis. However, at the present time, we are not dedicating any resources to exploring these other potential applications as they are beyond the scope of our development obligations with Schering.What’s the clinical status of AGW?
All 129 patients enrolled in our Phase 2 trial in Germany have completed the prescribed study procedures and we are now analyzing the results. We expect final reporting in mid-to-late calendar 2010. We’re hoping that if the results of this study are successful, we can approach regulators for the designs of pivotal studies for licensure. What’s important in this indication is that topical therapeutics for AGW now on the market can cause significant side effects so there is a need for better alternatives.And what’s the clinical status of cervical dysplasia?
We’ve completed a Phase 2 trial also in Europe with 41 patients and have met with European regulators. They wanted to be assured that there is no significant systemic penetration of the topical product. Our technology is not designed to deliver the substance systemically but, rather to deliver it epidemiologically. All of our preclinical data supports this, but they still wanted to see human data that shows no significant systemic penetration. So, we are now in a second Phase 2 study. In this pharmacokinetic study, the last patient out is expected this month, and preliminary findings from the first 10 patients showed no systemic penetration.What’s the market potential in cervical dysplasia?
Our indication is low-grade cervical lesions. There are over 1.4 million American women and roughly the same number in Europe each year presenting with low-grade cervical lesions. We feel that our product, based on encouraging early data, could address what is a very urgent medical need. But prior to low-grade cervical lesions, there is another indication: abnormal Pap smears. There are 55 million Pap smears performed every year in the U.S., and a percentage of those are abnormal before they are low-grade lesions. There is no pharmaceutical therapy for abnormal Pap smears and this indication dwarfs the 1.4 million cases of low-grade lesions. So, there is a pronounced need for a topical across the gamut of indications in this space.What’s the regulatory landscape in cervical dysplasia?
We’ve met with the FDA about the two trials in Germany and our intent to progress to a Phase 2/3 in the U.S. The pre-IND meeting gave us a sense of the required work prior to moving into this study. The FDA confirmed that the next study in this path would be the proposed Phase 2/3 study. In other words, it would be a pivotal study with Phase 2/3 designation in the U.S. We also confirmed in that meeting that a second study would be needed as a Phase 3 trial in Europe. So, the company’s intention is to progress to two filings – a Phase 2/3 in the U.S. and a Phase 3 in Europe – and pending outcomes, file for licensure. We expect to file the Phase 2/3 by this July 31, but we haven’t put a date on filing the European Phase 3 trial. The intention, however, is to file as quickly as possible after filing in the U.S.Give me an overview of your other platform L-DOS47.
It was conceived by Helix, has two U.S. patents and has the ability to destroy solid tumour tissue. The concept behind it was to make a targeted therapy, so we combined it with an antibody we obtained from the National Research Council. So we now have an L-DOS47 therapeutic that is very specific for non-small cell lung cancer. We see this opportunity, not only as a potential monotherapy, but also as a strong partnering platform, because the compound produces alkalinity of the tumour tissue. Many therapies today cannot access the cancer cell because of the acid content around the cancer cell. So, the concept is that if you use our agent together with your agent, perhaps we can promote greater uptake of your agent with fewer side effects by using a lower dosage.
We’re always keeping our options open but we want to add as much value as we can before we consider partnering L-DOS47.What’s the clinical path forward?
We have completed our production scale up to manufacture L-DOS47 for clinical trials, which was an important milestone this year. Our intention is to move into two early-stage studies: a U.S. Phase 1 and in Europe, a Phase 1/2 combined with chemotherapy and radiation. Since there is a lot of evidence to show that acidity around the tumour interferes with therapeutic efficacy, our concept is to show that combining our product with standard radiation or chemotherapy will show greater efficacy. The study in Poland with non-small cell lung cancer patients will have multiple arms: looking at the effectiveness of the drug as a monotherapy; the effectiveness in combination with chemotherapy; and the effectiveness in combination with radiation. In the U.S. Phase 1, we will study L-DOS47 as a monotherapy in solid refractory tumours.How much money do you need to finish all these studies?
At the end of our second quarter on January 31, 2010, we had about $20 million of cash, which will last us until approximately July of 2011.
But we definitely need to raise capital to execute our studies. The first two studies with L-DOS47 will be in the $10 million to $15 million range. The interferon studies will cost around $30 million. And that’s why we’re raising our profile in the U.S.
President and COO, Helix BioPharmaBorn:
December 7, 1969Education:
BSc. (Toxicology, 1993) and a M.Sc. (Pharmacology, 1995), University of TorontoCareer Highlights:
PriceWaterhouseCoopers Pharmaceutical Consulting Group, 1998-1999; Pharmaceutical Development Manager, Helix BioPharma, 1999; VP Corporate Development, Helix, 2002; President and Director, Helix, 2007
Disclosure: No Position