The Cuban adventure that landed a Malaysian biotech firm in the big leagues.

It all began in 2002 when Fidel Castro was president of Cuba. Malaysia enjoyed favourable bilateral relations with the republic, and a business partner invited Johan Indot to tag along with a commercial delegation seeking new business opportunities there.

A serial entrepreneur of sorts, Johan had by then co-founded two companies: a direct sales outfit which was sold off in the early 1990s, and Inoilco, an offshore marine services company servicing the oil and gas industry. He felt ready for his next venture, and the trip proved fruitful – they came back with plans to set up a company importing generic drugs for sale in Asean.

With waves of big pharma patents eventually set to expire, it seemed like a good idea. However, they soon learnt how tightly regulated the industry was. “We hadn’t understood the full complexity of it; the regulatory process was very strict,” Johan admits. The experience gave him some important insight into the workings of the pharmaceutical industry.

Johan: “It’s a unique opportunity for us to be in a business where we can make such a big difference to cancer patients and their families all over the world.”

Though the drug import business did not materialise, their contact with the Cubans led to another opportunity – the commercial rights to a potential lung cancer therapy under development. Today, Bioven – the company originally set up to enter the generic drug import business – has emerged as a dark horse in a drug development space dominated by big pharma.

Seated in the glass-walled meeting room of his Inoilco office in Plaza Damas, Kuala Lumpur, Johan is still the corporate face for his oil and gas business, but also the proud executive director of a front-runner in the targeted cancer immunotherapy space.

Interesting opportunity

When Bioven came across it in early-stage clinical trials targeted at non-small cell lung cancer, immunotherapy was an emerging concept. Epidermal growth factor (EGF) immunotherapy, as it is known generically, was developed by the Cuban Center of Molecular Immunology (CIM), a research institution in Havana.

Founded in 1994, CIM has a special focus on cancer immunotherapies, perhaps no coincidence in a country famed for its production of cigars, and where smoking rates – and prevalence of smoking-related cancers – are high.

Cuba has a mature bioscience research and biotechnology industry. Heavy investment in the sector was one way the Cubans adapted to half a century of US sanctions. This maturity has already benefited emerging players in the biopharmaceuticals space; Biocon, India’s largest biotech player, is a case in point.

In 2006, it acquired a CIM-developed anti-cancer drug called nimotuzumab. The drug, targeted at head and neck cancers, has become the first flagship brand in the company’s line of new oncology treatments.

It’s easy to see why Bioven, given the opportunity that same year to acquire the Asean market rights to another CIM-developed EGF immunotherapy, was tempted. It took the chance and has not looked back since.

Big pharma’s playbook

Working with the Cubans had its advantages, namely an unusually extensive data set accumulated over decades of research, Johan says. To really make things work, he realised they would need the right people on board.

The Malaysian Biotechnology Corporation helped put him on the right track, and eventually he got in touch with Steve Drew, a 30-year veteran of the global pharmaceutical scene. Drew had been vice president of Global Strategy at one of pharma’s big five firms, and came from the sort of corporate environment where “small fry” like Bioven get eaten for breakfast.

If anyone was in a position to help Bioven navigate the demanding and unmerciful world of pharmaceuticals, it would be Drew, who was offered the post of group CEO. Understandably, the offer to come on board as group CEO was greeted with caution.

“My immediate questions were: have they concluded proper diligence? Is the science of clinical and commercial value? What about manufacturing strategy?” Drew recounts.

Looking at preliminary data, Drew agreed they had something to work with. His conditions for coming on board were: three months of due diligence, hire the industry’s best consultants (the same ones used by big pharma) to go over the existing Cuban data and commission additional research to fill in any gaps.

Under Drew’s guidance, Bioven used every step in big pharma’s playbook to confirm if the drug would make the cut – Britain-based law firms, EU-qualified experts in manufacturing and meetings with key thought leaders in oncology.

They roped in top guns like the Swedish Karolinska Institute and Cancer Centre and Paul Erlich Institute in Germany for clinical research as well as law firms like JAG Shaw, Burns and Levinson, and Taylor Wessing for intellectual property matters.

At the end of the process, Drew was convinced – as were the company’s shareholders. Bioven bought up rights to the European market, and eventually the Austral and Middle East markets too.

Biomarkers

The investigational dossier it submitted to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) – the two regulatory authorities monitoring the drug’s two eventual target markets – consisted of 40% Cuban and 60% new data.

Bioven also obtained permission to start Phase III trials, which is where the drug is compared against current standards of care for that specific disease, but stopped halfway through recruiting patients because of new regulatory requirements.

“We made the decision to include a biomarker,” explains Drew. (Not all cancers are the same; a biomarker is a biological measurement used to detect what specific disease, and therefore treatment, a patient is likely to respond to.)

“Our immunotherapy is aimed at the EGF pathway (see sidebar Tailor-made treatments). So in this case, our biomarker would have to be something we could test for, to identify patients most likely to respond to treatment targeted at that pathway.”

Finding such a biomarker in itself entails additional investigation, which costs time and money. Again, the Cuban link paid off. It didn’t take long to find their biomarker from blood samples of patients who had responded positively to the treatment.

“Without a biomarker, the chance of success within a non-small cell lung cancer oncology trial is about 11%; with one, it’s about 62%,” Drew adds.

Gaining respect

Lung cancer, 85% of which is accounted for by non-small cell cancers, is by far the leading cause of death among cancer patients.

With biomarkers in place, Bioven’s drug was filed under an Investigational New Drug application, and obtained clinical trial approvals in Britain, Germany, the Czech Republic and Malaysia. Its applications are still under review in three other countries. (An approval could take as little as two years after trials begin.)

The company is in the midst of raising fresh funds to take it through Phase III trials in 71 centres across Europe and Asia. Getting both EMA and FDA approvals has been an important part of the plan. Bioven’s end goal is to attract buyers from the big pharma space.

Many global pharmaceutical firms want to bolster their immunotherapy portfolio. The health industry is also moving towards a future in personalised medicine; one where a cocktail of different immunotherapies targeted at different pathways may be combined and tailored to suit an individual’s needs.

Immunotherapies such as the one Bioven has on offer – should it get approved – are in high demand.

Finding its place

The industry has seen big changes in recent years.

Drew explains: “Most senior executives in pharma have lived through at least two or three mergers or acquisitions. Part of the transition has been a move to shed R&D and sales jobs, and to look outside at innovative biotech (firms) and academic institutions.”

Most acquisitions are made during the early stages of research with staggered payouts for each successful phase. Bioven, on the other hand, is seeing the drug development process all the way through. It will only solicit buyers once it has proven scientific support, due diligence and regulatory approvals.

Johan knows it’s too early to jump the gun. “But whether or not the drug succeeds, we are a small Malaysian company, and we got to internationally recognised Phase III trials.”

At the end of the day, there is only one set of rules in the industry – large or small, every company has to get through the same regulatory approvals.

“There are no shortcuts,” says Drew. “I’m proud to be associated with a group of Malaysian shareholders keen to lead, and take the risk (inherent) in this industry,” Drew adds.

Last year, the venture took on a new significance for Johan, who recently lost his father to cancer. “It’s a unique opportunity for us to be in a business where we can make such a big difference to cancer patients and their families all over the world,” he says. “Having experienced that myself, I know what it means.”

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