Xencor and Janssen Join Forces Against B-cell Lymphoma in a New Billion-Dollar Deal

Activating T-cells is an effective approach to target some types of cancers. However, regulating this activation is crucial. For example, a Phase 1 clinical testing of an anti-CD28 antibody resulted in life-threatening adverse effects.

With a new collaboration, Janssen and Xencor aim to develop CD28 antibodies that selectively activate T-cells to attack B-cell lymphoma cancer cells. The deal could potentially be worth more than a billion dollars. Xencor’s stock jumped almost 5.5% following the news.

Xencor’s proprietary XmAb antibody engineering platform allows them to modify the Fc domain of an antibody. This is the region that determines the immune function of an antibody. This will enable Xencor to regulate the cytotoxic, bispecific, and inhibitory activity of antibodies as well as extend their half-life.

Their platform has successfully produced 9 therapeutic candidates that are currently in clinical trials for a variety of oncology targets and autoimmune diseases. Their three most advanced products, currently in Phase 2 or Phase 1B/2 clinical trials, are:

• Vudalimab, a bispecific antibody that targets PD-1 and CTLA-4, for the treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC).
• Tidutamab, an antibody targeting SSTR2 and CD3, is currently in Phase 1B/2 for the treatment of Merkel cell carcinoma.
• Obexelimab, a CD19 antibody, for the treatment of Lupus.

A Billion-Dollar Deal

1) The development and commercialization of Plamotamab, one of Xencor’s antibodies currently Phase 1 clinical trials for the treatment of B-cell tumors, and 

2) The development of novel antibodies targeting B-cells by activating T-cells via the CD28 receptor.

As part of the deal, Janssen will receive worldwide rights for development and commercialization to Plamotamab. Clinical development costs will be shared between both companies on an 80/20 basis, with Janssen covering 80% of the cost. One exception to this cost-sharing agreement is the ongoing clinical trial testing of the combination of plamotamab, tafasitamab, and lenalidomide in patients with B-cell lymphoma. The Phase 2 trial for this collaboration is expected to begin in late 2021 or early 2022.

Additionally, Xencor will develop CD28 bispecific antibody candidates against B-cell targets. Janssen will have exclusive worldwide rights for select molecules. 

In return, Xencor could receive up to 1.313 billion, including $100 million upfront and an additional $25 million in newly issued shares purchased by Johnson & Johnson Innovation. The rest will be contingent on development, regulatory, and sale milestone payments. On top of this, Xencor will also receive royalties ranging from mid-teens to low-twenties.

“The treatment landscape in B-cell lymphoma will potentially be redefined by CD20 x CD3 bispecific antibodies, such as Plamotamab, and the best outcomes for patients will require creative combination approaches using complementary mechanisms of action. We are delighted to collaborate with Janssen’s leading scientists to expand the scope of the Plamotamab program, particularly as we explore opportunities to combine with novel B-cell targeted CD28 bispecific antibodies that can potentially selectively enhance T-cell cytotoxic activity,” said Bassil Dahiyat, Ph.D., President, and CEO at Xencor.

Author

Daniel Ojeda