Glaxo Deal Shows Antisense Starting to Make Sense for Pharma

March 31, 2010 Glaxo deal shows antisense starting to make sense for pharma

Lisa Urquhart

With its potential billion-dollar-plus deal with GlaxoSmithKline today, Isis Pharmaceuticals has cemented its position as the go-to company for antisense products, as this marks the 19th out-licensing or joint venture deal the company has inked since 2001.

As well as providing more confidence in the still relatively novel therapy area today’s deal should provide a welcome boost to Isis’ share price, which had fallen by almost 30% over the last six months, primarily on the back of less than positive data for its lead product mipomersen. Shares in Isis were 10% higher in early trading at $11.30.

Under the terms of this latest collaboration Glaxo has agreed to take six Isis antisense products in a range of therapy areas including infectious diseases and conditions causing blindness in return for an upfront fee of $35m as well as $20m in milestones per programme, up to proof of concept phase II. Glaxo has the option to license the products at this point, leaving Isis open to bank up to $1.5bn in license fees and milestone payments if, and only if, all six products make it to the market. Isis will also be in line for double-digit royalties on any marketed products.

Old hand

This move does not mark Glaxo’s first foray into the antisense space. As the table below shows the group already has a number of collaborations worth up to $2.82bn that it has signed over the last four years, including the $694m deal it signed last year with ProSense over six products, for indications including muscular dystrophy.

Today’s deal with Isis is, however, potentially Glaxo’s largest in the space, eclipsing the one it signed in October 2009 with Archemix worth $1.26bn, which included a $27.5m upfront fee and a $6.5m equity stake. GlaxoSmithKline antisense deals

Deal Upfront Status Current Milestones Product Deal Partner Deal Date Value Fee on Deal Status ($m) ($m) ($m)

PRO051/PRO044 ProSensa Phase II Phase II 13/10/2009 694 26 668

Aptamer Research Research Inflammatory Archemix 23/12/2008 1,259 24 1,235 project project Disease Project

Inflammatory microRNA Research Pre- Regulus Therapeutics 17/04/2008 593 15 573 Research project clinical Project

Viral Antisense Research Pre- Research Santaris Pharma 19/12/2007 148 3 140 project clinical Project

Pre- SPC3649 Santaris Pharma Phase I 19/12/2007 127 5 122 clinical

Respiratory GlaxoSmithKline/Sirna Research Research RNAi 04/04/2006 - - - Therapeutics project project Therapeutic

Total 2,822 73 2,739

The increasing number of deals struck in this field by big pharma over the last five years illustrates the growing interest; activity peaked in 2008 before the financial crisis struck. However, Roche’s interest in the field meant that the group was in 2009 willing to spend what had until today been the largest amount on an antisense deal, when it inked a deal worth up to $1.21bn with Alnylam over several cancer products (Partners sensing potential in Antisense, April 4, 2008).

Antisense product deals per year

Deal Year Count

2010 (YTD) 3

2009 11

2008 30

2007 23

2006 22

Total 89

However, while companies definitely see potential in the therapy, that works by binding to messenger RNA to inhibit the production of proteins that cause disease, what has changed is the amount of money they are prepared to chance on this still very experimental field, with modest upfront fees and heavily back ended deals appearing to be the norm.

Glaxo itself has struck one of its increasingly common option deals for the six Isis products. This also mirrors a similar deal the UK pharma group struck with ProSense last year.

This caution may be due to some of the earlier deals struck in the field, most notably Genzyme’s now very expensive looking deal with Isis over mipomersen, which included a $175m upfront fee and a $150m equity investment. This has only recently started to look as if it might stand a chance of getting to market in what is still a relatively young and largely untried field (Isis inks key deal with Genzyme, January 8, 2008).

To date there has only been one other marketed product, Isis and Novartis' Vitravene, a treatment for cytomegaloviris retinitis in AIDS patients which was approved in 1998 but subsequently withdrawn after more effective treatments kept patients healthier, thereby avoiding the eye condition.

As the table below shows mipomersen is the next antisense product most likely to make it to market, and the only one that analysts have so far assigned forecasts to.

But with more and more big pharma companies betting on the space, albeit with small initial stakes, the field could rapidly see a number of new products progressing over the next few years.

Late stage antisense products

Product Company Pharmacological Class Phase

Novartis/ Isis Vitravene Cytomegalovirus (CMV) antisense Withdrawn Pharmaceuticals

Genzyme/ Isis Apolipoprotein B-100 (ApoB-100) Mipomersen Phase III Pharmaceuticals antisense

Alicaforsen (ISIS 2302/AP Isis Pharmaceuticals ICAM-1 antisense Phase III 1007)

Genasense Genta Bcl-2 antisense Phase III

AP1007 Sigma Pharmaceuticals ICAM-1 antisense Phase III

Bevasiranib OPKO Health VEGF RNAi therapeutic Phase III

Trabedersen Antisense Pharma TGF-beta2 antisense Phase III

Alicaforsen (ISIS 2302/AP Atlantic Healthcare ICAM-1 antisense Phase III 1007)

GS-101 Gene Signal IRS-1 antisense Phase III