Cell therapy growth and pains: Investment, collaboration, and controversy

May 1, 2016
Cynthia A. Challener
Cynthia A. Challener

Cynthia A. Challener, PhD, is a contributing editor to BioPharm International.

BioPharm International, BioPharm International-05-01-2016, Volume 29, Issue 5
Page Number: 18

Cell therapy companies are attracting interest from investors, and drug companies are seeking partnerships and acquistions to accelerate development.

Cell therapy companies are attracting interest from investors, and drug companies are seeking partnerships and acquistions to accelerate development. Juno Therapeutics, Kite Pharma, and Novartis are considered the leading developers of engineered T-cell therapies, although most large biopharma firms have initiated research efforts and are partnering with small biotech companies specializing in chimeric antigen receptors (CAR)-T cell and gene-editing technologies. 
Juno’s initial public offering (IPO) of $264.6 million was the largest biotech IPO in 2014, and within one month the company’s valuation more than doubled from $2 billion to $4.7 billion (1). In May 2015, Juno expanded its pipeline with the acquisition of German biotechnology company Stage Cell Therapeutics for approximately $59 million. Juno then entered into a 10-year partnership with Celgene to develop and commercialize immunotherapies for the treatment of cancer and autoimmune diseases in June 2015, for which Celgene paid a total of $1 billion. In January 2016, Juno acquired acquired AbVitro, a privately held biotechnology company based in Boston. In early April 2016, Juno announced that it formed a new cell therapy company in China--JW Biotechnology (Shanghai) Co.--with WuXi AppTec (2). Juno is also in collaborations with the Fred Hutchinson Cancer Research Center, the Seattle Children’s Research Institute, and the Memorial Sloan Kettering Cancer Center in New York and has additional agreements or partnerships with Editas Medicine, Sanofi, Five Prime Therapeutics, and Sutro Biopharma, among others.
Novartis created the Novartis Cell and Gene Therapy Unit (CGTU) and has an exclusive global collaboration with the University of Pennsylvania (Penn) to research, develop, and commercialize targeted CAR immunotherapies for the treatment of cancers. The collaboration was initiated based on CAR research conducted by Carl June and Penn with CTL019, which targets a protein called CD19 and is under investigation in a number of B-cell malignancies. For the manufacture of CTL019, Novartis purchased the first FDA-approved GMP-quality site for cell-therapy production in late 2012 from Dendron Corporation. According to Eric Althoff, head of global media relations with Novartis, the company has a goal to file a biologics license application (BLA) for CTL019 in pediatric r/r ALL and r/r DLBCL with FDA in 2017. Penn recently unveiled its new $27-million-dollar Novartis-Penn Center for Advanced Cellular Therapeutics, which will focus on CAR-T cell therapies. Novartis invested $20 million in the center (3). 
The rapid development of the cell therapy market segment is not without controversy. June, who was widely recognized for his role in developing T cell therapies, in March 2016 made corrections to three articles in the New England Journal of Medicine to acknowledge that the actual DNA was developed by researchers at St. Jude Children’s Research Hospital (4). 
In April 2015, Juno Therapeutics reached a settlement with Novartis over the T-cell manipulation technology used in the creation of CAR-T immunotherapies. The litigation began as a contract dispute in 2012 between St. Jude’s Research Hospital and Penn and was expanded to include a patent. Juno became a party to the litigation through a 2013 license agreement with St. Jude to use the patent. Novartis entered into a partnership with Penn to develop CAR-T therapies in 2012. Novartis will pay Juno $12.25 million upfront and milestone payments and royalties from net sales of Novartis’ CTL019. Juno will share the payments with St. Jude based on the terms of their contract (5). 
In February 2016, Precision Biosciences announced that it is also involved in a global collaboration with Baxalta to develop a broad series of allogeneic CAR-T cell therapies. The partnership combines Precision BioSciences’ ARCUS gene-editing technology with Baxalta’s global infrastructure, expertise, and growing immuno-oncology portfolio with the goal of developing disruptive treatments for underserved cancers. Precision BioSciences will receive an upfront payment of $105 million from Baxalta, with additional option fees, developmental, clinical, regulatory, and sales milestones, potentially totaling up to $1.6 billion, plus royalties on worldwide sales (6).

References
1. T. Soper, “Juno Stock Skyrockets After Celgene Invests $1 Billion to Change the Way Cancer Is Treated,” GeekWire (June 29, 2015).
2. Juno Therapeutics, Press Releases, www.junotherapeutics.com.
3. University of Pennsylvania, “Novartis-Penn Center for Advanced Cellular Therapeutics Unveiled at Penn Medicine,” Press Release (Philadelphia, PA, Feb. 16, 2016).
4. A. Regalado, “T-Cell Pioneer Carl June Acknowledges Key Ingredient Was’t His,” MIT Technology Review, March 14, 2016.
5. R. Hernandez, “Novartis and Juno Settle Over CAR-T Therapy Technology,” BioPharmInternational.com, April 7, 2015.
6. Precision Biosciences, “Baxalta and Precision BioSciences form Global Genome Editing Collaboration in Immuno-Oncology,“ Press Release (Durham, NC, Feb. 25, 2016).

Article DetailsBioPharm International
Vol. 29, No. 5
Page: 18

Citation: When referring to this article, please cite it as C. Challener, "Cell therapy growth and pains: Investment, collaboration, and controversy" sidebar to "Realizing the Potential of CAR-T Cell Therapies," BioPharm International 29 (5) 2016.