ImmunoGen, the US-based company developing targeted anticancer therapeutics using its proprietary Targeted Antibody Payload (TAP) technology, has added Novartis to its stable of big pharma partners in the field.

Under a collaboration agreement to discover and develop antibody drug conjugates (ADCs) for cancer, Novartis will pay ImmunoGen a US$45 million fee upfront for exclusive rights to combine the TAP technology with antibodies to several as yet unnamed antigen targets.

For each of these targets that results in an anticancer therapeutic, ImmunoGen will be entitled to receive milestone payments potentially totalling US$200.5 million, as well as royalties on any ensuing product sales.

ImmunoGen also stands to get financial compensation for research and any manufacturing it does on behalf of Novartis. The Swiss company is responsible for the development, manufacturing and marketing of any products that emerge from the collaboration.

Top three

As ImmunoGen pointed out, the new agreement means it now has partnerships with the pharmaceutical industry’s top three oncology antibody-based therapeutic companies, Roche/Genentech, Sanofi-Aventis and Novartis.

The collaboration demonstrates “that antibody drug conjugates are a ‘must-have’ weapon in the product arsenal of big pharma cancer companies and that ImmunoGen is the leading source for them”, the company said.

TAP compounds consist of a tumour-targeting manufactured antibody with one of ImmunoGen’s proprietary, highly potent cancer-killing agents – as much as 1,000 to 10,000 times more powerful than traditional chemotherapy drugs, according to the company – attached as a payload.

Seven such compounds are now in clinical trials through ImmunoGen’s own product programmes and those of its partners, which also include Amgen, Bayer Schering Pharma, Biogen and Biotest. ImmunoGen sees these partnerships as a vital revenue source for its own efforts.

“ImmunoGen has a valuable technology, and we’re committed to developing our own pipeline of anticancer therapeutics,” commented president and chief executive officer Daniel Junius on the Novartis agreement. “Our partnerships provide funding support for out internal product programmes and further development of our technology. We plan to continue to establish new collaborations on a selective basis.”

T-DM1 progress

The most advanced TAP compound is T-DM1, currently in Phase III clinical trials under ImmunoGen’s collaboration with Genentech/Roche.

In July, Roche filed a Biologics Licence Application (BLA) with the US Food and Drug Administration for T-DM1, an ADC that combines Genentech’s HER2-targeting antibody, trastuzumab (Herceptin), with ImmunoGen’s DM1 cancer cell-killing agent to treat patients with advanced HER2-positive breast cancer who have previously received multiple HER2-targeted medicines and chemotherapies.

Unusually, the submission was based on the results of a 110-women Phase II clinical trial, which showed that T-DM1 shrank tumours in 33% of women who had already received seven drugs on average for advanced HER2-positive breast cancer. In August, however, Roche announced that the FDA had issued a Refuse to File letter denying the trastuzumab-DM1 combination accelerated approval. The company now expects to file T-DM1 worldwide in mid-2012.

In the meantime, last Friday ImmunoGen reported positive interim clinical data with T-DM1 for the first-line treatment of HER2-positive metastatic breast cancer at the 35th European Society for Medical Oncology (ESMO) meeting in Milan, Italy.

The initial findings were from a 137-patient randomised Phase II clinical trial comparing T-DM1 with trastuzumab plus chemotherapy (docetaxel) for the treatment of HER2-positive metastatic breast cancer not previously treated with chemotherapy. Herceptin plus chemotherapy is the current standard first-line therapy in this setting.

The objective response rate for patients treated with T-DM1 was 47.8% versus 41.4% for patients treated with Herceptin plus chemotherapy, with a minimum of 5.9 months’ patient follow-up, ImmunoGen said. Final data on progression-free survival – the trial’s primary endpoint – are expected in the second quarter of 2011.

Of particular note, ImmunoGen added, was that the incidence of more serious side-effects (Grade 3 and higher) seen with T-DM1 was around half that reported with trastuzumab plus docetaxel (37% vs. 75% respectively), with no increased risk of cardiotoxicity. 

Financial guidance

The company has also announced updated financial guidance for its fiscal year ending 30 June 2011. Net cash used in operations is now expected to run between zero and US$4 million, with net loss projected at US$60-US$64 million.

Cash and marketable securities at the fiscal year-end should total between US$106 million and $110 million, which should be enough to fund operations through ImmunoGen’s 2013 fiscal year, the company said.