Teaching old drugs new tricks

30-09-2013

Teaching old drugs new tricks

Developing new drugs is time-consuming and expensive. DelMar Pharma researches old drugs and establishes new IP around them to streamline the process. LSIPR spoke to chief executive Jeffrey Bacha about the company’s approach.

For a variety of reasons, some drugs disappear into pharmaceutical obscurity. Problems with IP licensing, toxicity, or lack of understanding about the mechanism of a drug at the time of its discovery may all be to blame, though some of these abandoned medicines can be picked up by new companies and repurposed or repositioned for use within the context of modern care where unmet needs remain.

In December 2011, the US-based National Institutes of Health established the National Center for Advancing Translational Sciences (NCATS) to accelerate the development of new treatments for patients by using old knowledge about the causes of diseases.

The benefits of researching known disease-driving mechanisms and making modern treatments from them are plain: according to the NCATS website, developing new drugs, from discovery of the therapeutic target to the approval, takes an average of 14 years, and the cost per successful drug is about $2 billion, adjusting for all failures.

Using this old knowledge and building new IP around it streamlines the process of bringing a drug to market, and offers a range of benefits to both investors and patients. It’s a model adopted by California-based pharmaceutical company DelMar Pharma. “We’re interested in the mechanism of the drug and its broad-reaching potential opportunities,” says Jeffrey Bacha, chief executive of DelMar Pharma.

“From there we look at where the needs are based on that mechanism and work on those areas as quickly as possible.”

One famous success story of repurposing old drugs is that of thalidomide. Once prescribed as relief for morning sickness in pregnant women, by 1961 it was linked to severe birth defects and later withdrawn from general use.

Pharmaceutical company Celgene later picked up on another mechanism behind the drug. It found thalidomide to be effective when taken in combination with dexamethasone in the treatment of multiple myeloma, a type of cancer, and in February this year Celgene received approval from the US Food and Drug Administration to market thalidomide derivative pomalidomide (branded as Pomalyst).

Benefits

This model of identifying old drugs where the clinical and commercial data already exists allows DelMar to leverage previous investment into products, and offers a good understanding of a drug’s safety profile. For example, DelMar’s lead drug candidate, VAL- 083, already benefits from a safety database of more than 1,000 patients in the US.

While it is still necessary to carry out clinical trials, which depending on the type of indications of the drug can be very large, understanding a drug’s mechanism and safety profile will reduce the time taken to bring the product to market.

“Looking at it in American football terms, you’re starting from midfield versus your own 20-yard line, so the pathway is potentially much shorter,” Bacha says.

Bacha cites another rediscovered drug success story—leukaemia treatment bendamustine was “sitting on the shelves of the National Cancer Institute (NCI)”, even though it had been commercialised in Eastern Europe. It now has sales of nearly $1 billion a year.

IP portfolio

DelMar Pharma looks at the mechanism behind old drugs and considers how it may be applied in the context of modern care. Bacha says there are opportunities to build new IP around molecules where the composition of matter is known, and the discovery of new applications for the molecules allows for the development of modern treatments. He describes it as “wrapping new IP around old information, new understandings and new data”.

So far DelMar Pharma has filed seven new patent applications related to VAL-083, and in July this year it received its first US patent covering a method of manufacturing the drug.

Bacha is confident DelMar will be granted additional new patents soon. “We would expect, based on the fact that we’re following the recipe of previously successful filings, that we will have a number of claims issued that will provide new patent protection for VAL-083 beyond 2030,” he says.

DelMar’s patent claims range from covering new uses of the drug to new understandings of its mechanism, as well as chemical compositions.

“Our strategy is based on others who have gone before us, who have taken old drugs, taught them new tricks and built successful patents around them,” Bacha says.

“Looking at it in American football terms, you’re starting from midfield versus your own 20-yard line, so the pathway is potentially much shorter.”

VAL-083 has also been designated an orphan drug—a therapy that treats rare conditions— by the FDA and EMEA, so even if the company doesn’t receive all the patents it applied for, the drug has been granted seven years of market exclusivity in the US and 10 years in Europe, respectively.

Bacha says the company is always looking for opportunities to in-license patents: “In terms of in-licensing for VAL-083, there hadn’t been much activity because the drug is old enough that the information we were starting with was generally in the public domain and we built IP around that.

“But we’re always looking for the next opportunity as we think about our pipeline, and we’ll certainly keep our eyes open from that perspective.”

As well as its pending patents, DelMar has trade secrets that cover the screening process where drug candidates are identified, and the process of manufacturing and scaling up the VAL-083 compound. “Part of this screening and identification is quite proprietary to us,” Bacha says.

VAL-083

VAL-083 is being developed as a treatment for glioblastoma multiforme, an aggressive form of brain cancer. Glioblastoma is a refractory cancer, and patients are failed by the available therapies because the tumour has become resistant to intervention.

“VAL-083 is a drug that was studied fairly extensively at the NCI, in what we call the original war on cancer of the late 1970s and early 1980s,” Bacha says.

“For various reasons it was never commercialised at that time but it seemed to have some very interesting activity in a number of different tumour types, including glioblastoma,” he continues. The drug is capable of passing the blood-brain barrier which, he says, is rare.

The “significant unmet need” for a glioblastoma treatment is what sparked the DelMar team’s interest in the drug. The team later learned that the drug had already been approved in China for the treatment of chronic myelogenous leukaemia and lung cancer, a “serendipitous development”. “We can leverage data and impact patients much sooner there than anywhere else in the world.”

The company’s co-founder Dennis Brown had been in the business of discovering and developing novel cancer therapies for many years, Bacha explains. Brown developed a screening tool, looked at a number of different databases, including the NCI database, and identified a handful of potential molecules, including VAL-083. Some of Brown’s research led to the formation of new pharmaceutical companies, including Matrix Pharmaceuticals and ChemGenex.

VAL-083’s history makes the licensing process more interesting. Chemically speaking, VAL-083 is a first-in-class chemotherapy with a broad clinical history, he says.

DelMar works with a primary US-based law firm, generally prosecuting patents under the Patent Cooperation Treaty. “Our law firm in the US has relationships with the other jurisdictions that we’re pursuing,” Bacha says, “so we’re able to leverage that very quickly.”

Personalised medicine

Another part of DelMar’s business strategy is looking into personalised medicine, though it’s taking a novel approach. “Many companies, even patients, have begun thinking about personalised medicine by asking: ‘How do I know this drug is right for me?’” Bacha says.

“We ask: ‘How do I know this drug is going to benefit what patient?’”

He refers to a diagnostic process that can determine whether a certain drug may be used to treat glioblastoma (GBM). Glioblastoma is usually treated with a combination of the drug temozolomide (Temodar) and radiation, although this method has been found to benefit only 30 to 40 percent of patients.

A method that can identify these patients and would allow the company to put its own therapy forward as a first line treatment for them is already part of the treatment paradigm. A lot of companies are beginning to focus on the diagnostic process, but DelMar Pharma has the benefit of a potential companion diagnostic already in place, Bacha says.

Future direction

DelMar Pharma has just one drug on the books, though this is by design, Bacha says. “When we started the company, we made a conscious decision to build the company around one drug, focused on glioblastoma.

“We’ve got a small, very experienced team and want to point all the energy in one direction,” he explains. Keeping the company compact and focused on one drug also makes it easier to acquire, Bacha says, as there are no other products and assets to deal with in the transaction.

Courtesy of Brown’s work in drug discovery, the team has other molecules on the backburner that it can bring to the table if the situation changes: “There are assets we will be able to bring into the pipeline very rapidly,” Bacha says.

“If DelMar were to be acquired, the team would simply go and pull another product out of the garage and start to work on the next adventure.”

DelMar Pharma, IP strategy, repurposing drugs, pharmaceuticals, cancer