Event - ImmunoGen's antibody drug conjugates shaping up for scrutiny

The approaching American Society of Hematology (Ash) meeting fires the starting pistol on a period promising very interesting news from Massachusetts-based ImmunoGen, a company that has invested heavily in the growing field of antibody drug conjugates.

First up is phase I data at Ash on three products that employ the company’s “targeted antibody payload” (TAP) technology, providing the first chance to scrutinise clinical stage data on two of these promising candidates, which have already been licensed by big partners. However, these data could well be overshadowed by results from a phase II trial of Roche partnered trastuzumab-DM1, which are due to be revealed a few days later at the San Antonio Breast Cancer Symposium (SABCS). The study was in the very tough third-line breast cancer setting which means positive data at this stage could well be enough to win a marketing license, something that would certainly represent a significant event for ImmunoGen.

Combination killer

T-DM1 is a combination of ImmunoGen’s maytansinoid, a potent cancer cell killing agent called DM1, and Herceptin (trastuzumab), and as such is being trialled in HER2 positive metastatic breast cancer.

As well as third line, the drug is being examined in other settings; a second-line phase III study called Emilia began in February this year looking at T-DM1 versus Roche’s Xeloda used in combination with GlaxoSmithKline’s Tykerb. In the first-line setting a phase II study is underway, pitting T-DM1 against Herceptin plus Taxotere.

With results from the Emilia trial not due until 2012, the third-line setting certainly represents the swiftest route to market for this drug, assuming the data at SABCS is positive.

In a previous trial, T-DM1 showed a 24% overall response rate in metastatic patients refractory to Herceptin and Tykerb, and the hope is that outcome will be replicated. Analysts at RBC Capital Markets commented today that a response rate of 20% would be positive, but given the indication the drug could be approvable even with a response rate in the low teens.

Should the drug perform well Roche is likely to file for approval early in 2010, meaning it could well be on the market by the end of next year, if all goes well, and valuable royalties for ImmunoGen.

Slow progress

T-DM1 is the result of a licensing deal signed with Genentech originally, back in 2000. Progress has not exactly been swift and serves to illustrate how difficult the field of antibody drug conjugates has proved to conquer. An analysis conducted by EP Vantageearlier this year found a healthy development pipeline, but at the same time a field littered with failures (Therapeutic focus – Antibody drug conjugates set to improve on poor track record, May 29, 2009).

Whilst the theory is logical and compelling, combining the power and selectivity of monoclonal antibodies with a toxic agent to deliver an even more powerful blow to malignant tumours, toxicity and drug resistance issues have been hard to overcome.

As such, the phase I data at Ash will also be important in building confidence in ImmunoGen’s approach to these problems.

Partnered products in the spotlight will be SAR3419, being developed with Sanofi-Aventis and put through a trial in patients with relapsed or refractory B-Cell Non-Hodgkin’s Lymphoma, and BT062, in a study of patients with relapsed or refractory multiple myeloma, partnered with Biotest. Neither of these products have generated clinical data to date, and hopes are high for encouraging signals.

Additionally, data on an internally developed candidate called IMGN901 will be presented, an antibody drug conjugate consisting of DM1 attached to a CD56-binding antibody. Encouraging phase I results were announced in November in six Merkel cell carcinoma patients, one of whom achieved a complete response (CR) and remained in remission for more than four years. The Ash data is from a trial in multiple myeloma and if positive would support the company’s plans to run an extension study using IMGN901 in combination with Revlimid and dexamethasone.

On a higher plane

With the breadth of data due at Ash, a good showing will provide ImmunoGen with a well needed boost of confidence. Shares in the company climbed 18% in November suggesting that many in the market are anticipating a good showing.

Analysts covering Roche have already started to pencil in sales forecasts for T-DM1, $47m by 2014 according to consensus data from EvaluatePharma, another sign of growing confidence.

Shares in ImmunoGen were trading at $7.72 in early trade today, valuing the company at $465m. That is shy of the $9.99 touched in July, but still a long way above $4.29, where the stock started 2009. If the data goes down well over the coming weeks, ImmunoGen shares should start 2010 at a considerably higher level.

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