May 15, 2009 (Vol. 29, No. 10)

From Collaborations to In-Licensing to M&A Activity, Firms Are Benefiting from Alliances

When times are tough, partnering is more important than ever. The “BIO-Europe Spring” conference, held in Milan recently, attracted 1,550 international biotech and pharma delegates who engaged in over 7,000 partnering meetings, a 21% increase over last year’s event. 

“The marketplace of the next ten years is going to be dramatically different,” explained Steven Burrill, CEO of Burrill & Co. “We built biotech mainly on the healthcare side—most of the capital went into oncology and cardiovascular disease because people thought they could make money. But green and white biotechnology are now getting more attention.”

On the whole, Burrill’s outlook was optimistic—he calls the current situation a sea change and says this is generally a change for the better. “We will be a stronger industry in the end than we are today,” he promised. 

However, Burrill admitted that much had happened in the last year and a consumer credit crisis—to follow that experienced by the banks—is now looming.  Each country is experiencing recession in its own way and this could last for five to ten years, he added. Healthcare systems, too, are going through dramatic change. 

Regulation is a barrier to the biotech and pharma industry, he noted. The regulators are increasingly interested in pharmacovigilance, which can mean taking products off the market. The industry, of course, wants to keep them on the market. The U.S. will become pro-generics and anti-innovation, he predicted.

In reality, healthcare systems have not changed for 2,000 years—people wait to get sick—it is only the tools and technologies that have gotten better. But between now and 2020 everything will change, Burrill said. He believes there will be WalMart-style delivery of products like genetic screening, and that we will enter a “consumer, digital, healthcare world,” in which diagnostics will be based upon information being sent via iPod or Blackberry to a lab.

“All of these technologies exist already—we just need to integrate them,”  he added. These efforts will lead to the customization of healthcare based upon e-records and smart cards. Indeed, some countries, like The Netherlands are already making significant progress in this direction.

This new patient-centered healthcare model has many implications for the industry. Prescriptions will likely be tied more to diagnostic results, and lower margins will likely be seen on ethical drugs. Patents will be devalued, and big pharma will become more focused upon production and distribution. Research and development will move to Asia, and there will be international regulations. “Every company will have to be global from day one,” Burrill said. 

As far as the Wall St. implosion is concerned, after 30–40 years of access to cheap capital, financing is now harder to find and more expensive. VCs have deep pockets, but short arms. “Buy side is not interested in microcap companies worth less than $1 billion,” Burrill explained.

“We have created extraordinary value,” he concluded. “There is capital. It is just more expensive. And there will be another IPO market, but it will be different. Wall St. will be back in 2010 to 2011—but will not finance what it has historically. And finally, physical cluster will become less important, but there will be more virtual clusters.”

The primary catechin in Polyphenon Pharma’s Polyphenon E, epigallocatechin gallate (EGCG), has been shown to affect many processes in the body related to abnormal cellular activity that can lead to cancer.

Patent Cliff

Ben Bonifant, vp and head of the business development practice at Campbell Alliance, focused upon the “patent cliff” faced by pharma. More than $60 billion of current revenues will be lost by drugs going off patent by 2011. Meanwhile, one-third of biotechs have less than one year of cash, but they have an ample supply of late-stage products, he said.

Campbell Alliance has conducted research on how many of these advanced products are actually held by companies in distress. If financing does not open up and licensing does not increase there will be dire consequences for some, Bonifant said. He also noted that H2 08 saw a decrease in large Phase II deals and this is “troubling”; there were only eight of these in 2008 compared to 19 in the same period of 2007. 

It might be that the industry’s burgeoning Phase II pipeline is making companies more choosy. Also, cost-cutting, including layoffs, may be putting people off. In tough times, there is also the problem of the “leaking pipeline,” when companies don’t develop products and time eats away at their patents.

Pam Demain, executive director, corporate licensing at Merck, said that the merger with Schering-Plough gave the combined firm a great pipeline and a number of later-stage assets, but the firm would not stop licensing. “We are in a good position to survive as we are active in M&A and in licensing,” she added. However, if the company licensed a compound earlier than Phase IIb, it would have to be a high-quality compound. She noted that companies are now coming up with more realistic ideas and are more flexible because of the current financial situation. 

Biotech Firms

Ablynx is “one of the few biotech companies in Europe that is expanding at a fast pace now,” explained  Eva-Lotta Allan, CBO. The firm has three molecules based upon its Nanobody® platform technology in the clinic. Nanobodies are based upon the heavy chain-only antibodies produced by camelids. They can be described as “large small molecules” as they are just one-tenth the size of a conventional antibody and, as such, can penetrate tissue well. They are also resistant to degradation, Allan explained. These characteristics make them amenable to alternative delivery methods.

Lead product ALX-0081, which recently achieved its primary endpoint in a Phase Ib study, is an antithrombotic product that targets von Willebrand factor. ALX-0081 is expected to carry a lower risk of bleeding than other antithrombotics, Allan reported. A subcutaneous version, ALX-0681, entered Phase I in December.

Nanobodies have been validated in over 100 targets, including GPCRs, and over 25 animal models. Ablynx has validating deals with Novartis, Boehringer Ingelheim, Merck Serono, and Wyeth.

Polyphenon Pharma is a privately held subsidiary of Misui Norin. The parent company discovered and carries out cGMP manufacture of Polyphenon E®, a defined mixture of catechin polyphenols from green tea, while Polyphenon Pharma is developing it as a pharmaceutical product for the treatment of various unmet medical needs. 

The use of Polyphenon E in a topical formulation for the treatment of HPV-caused genital warts was licensed out to Medigene. Medigene’s topical compound Veregen®, in which Polyphenon E is the active ingredient, was reportedly the first product approved under FDA’s new botanical drug regulations.

The science behind Polyphenon E comes from epidemiological studies indicating that green tea polyphenols can protect against cancer. One mechanism that could explain such a protective effect was recently advanced by researchers at Columbia University. They demonstrated that polyphenols disrupt the lipid raft of the cancer cell’s membrane, disrupting the activation of the EGF receptor, which increases apoptosis and decreases proliferation.

The company is developing Polyphenon E as an oral treatment for high-grade prostatic intraepithelial neoplasia (HGPIN), a precancerous condition. If HGPIN is found in a needle biopsy, there is a 30–50% chance of the patient developing prostate cancer in the next five years, the firm reported. 

According to Stig Ogata, Polyphenon Pharma’s COO, in an Italian study where HGPIN subjects were treated with green tea catechins, progression to prostate cancer occurred in 9 patients out of 30 in the placebo group, but in only 1 patient out of 30 in the treatment group. A Phase II trial is currently under way.

Polyphenon  Pharma is also developing an oral treatment for chronic lymphocytic leukemia. In a Phase I study, Polyphenon E showed an excellent safety profile and indications of efficacy in reducing lymphocyte designation for this indication, Ogata added.

ALX-0081, Ablynx’ lead product, is an antithrombotic that targets von Willebrand factor.

Susan Aldridge, Ph.D. ([email protected]), is a freelance science and medical writer specializing in biotechnology, pharmaceuticals, chemistry, medicine, and health.

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