By Brady Huggett

If you can¿t beat ¿em, join ¿em.

That might be the case when considering Isis Pharmaceuticals Inc. and anyone else trying to forge a path in antisense. It certainly was with Antisense Therapeutics Ltd.

Isis and Circadian Technologies Ltd. helped form Melbourne, Australia-based Antisense Therapeutics Ltd. (ATL), a now-public company focused on discovering and developing antisense drugs, thus stretching Isis¿ antisense reach to the land Down Under.

ATL, spun out by Circadian, completed its initial public offering Wednesday, selling 65 million shares at A20 cents apiece, raising about A$13 million (US$6.6 million). The company was capitalized at A$43 million at the issue price and is now listed on the Australian Stock Exchange under the symbol ANP.

The money will provide ATL with the financial means to begin its public life, and Isis and Circadian now hold about 14 percent and 36 percent of the company, respectively. The financial support is pleasing, but perhaps more important in this field is the help and blessing of Carlsbad, Calif.-based Isis, said Stanley Crooke, its CEO and chairman.

¿I look at ATL and [our recent collaboration] with OncoGenex, and to the things we are likely to do, and what is similar is that we have a dominant position in antisense,¿ Crooke told BioWorld Today. ¿When companies get involved in antisense, they pretty quickly decide that it is better to work with us than not.¿

Isis¿ intellectual property includes what Crooke has called ¿everything that is important in antisense,¿ something achieved when Isis and Hybridon Inc., of Cambridge, Mass., settled their patent conflicts through a deal done in May that gave Isis access to all of Hybridon¿s patents for about $34.5 million. Hybridon paid Isis $6 million in stock, to be sold over three years, and got access to Isis¿ RNase H suite of patents, but since that time, there has been little dispute about who controls antisense: Isis does. (See BioWorld Today, May 29, 2001.)

And with that domination comes responsibility. Isis would like to see others working in the field do well, specifically because whatever research done can boost or harm the industry¿s opinion of antisense, Crooke said.

¿We get to participate in the science and do it in a positive way, and that matters to us,¿ he said. ¿It is difficult to do antisense without encroaching on our patents. [ATL] came to us, and so did OncoGenex, but in the future, I think we will be a little more active in fostering these relationships.¿

As part of the agreement, Isis licensed ISIS 107248, an antisense inhibitor of CD 49d, a subunit of VLA-4 (very late antigen-4), to ATL. ATL is free to develop the compound for whatever indication it desires, but Crooke said it might be most directly applicable in multiple sclerosis. Isis will complete the preclinical studies for the compound and will manufacture the drug for clinical trials ¿ to be conducted by ATL ¿ at ATL¿s expense.

Also, Isis and ATL will participate in a five-year antisense collaboration that includes ATL¿s use of Isis¿ GeneTrove gene functionalization services for a limited number of targets.

Crooke said that ATL¿s Australian location provides Isis access to another public market. But while Isis owns 14 percent and has an option for additional shares, Crooke said Isis ¿would never become anything but a minority shareholder¿ in ATL.

Isis pipeline is filled with 13 products. Two of them ¿ ISIS 3521 and ISIS 2302 ¿ are in Phase III trials for non-small-cell lung cancer and Crohn¿s disease, respectively. It has seven products in Phase II trials. Isis has been impressive in the later months of the year, signing a $400 million-plus deal with Eli Lilly and Co., of Indianapolis, in August; raising $100 million in October; signing a deal with OncoGenex and initiating a Crohn¿s disease Phase III trial in November; and entering a collaboration with Amgen Inc., of Thousand Oaks, Calif., this month. (See BioWorld Today, Aug. 23, 2001; Nov. 27, 2001; Nov. 30, 2001; and Dec. 14, 2001.)

¿It¿s a deal a day; it¿s been a great year,¿ Crooke said. ¿I think the world has begun to realize the potential of antisense. As that has been recognized, more and more opportunities come our way. This [collaboration] is a manifestation of that progress that has been made in the technology and our position in it. It makes sense for us to try to exploit our position in it in any way we can, and this is one of those ways.¿