The regenerative medicine sector that embraces gene and cell therapies continues to expand, particularly on the business and clinical development fronts. For example, a panel at the Neurosciences 2018 conference discussed just how rapidly the science is evolving and now beginning to take on harder-to-treat diseases, with gene therapies already in early stage development targeting amyotrophic lateral sclerosis, Parkinson's disease and Batten disease.
According to the third-quarter 2018 report released by the Alliance for Regenerative Medicine (ARM), the Washington-based organization that advocates and supports the global development of regenerative and advanced therapies, the sector has grown almost 5 percent since the beginning of the year, with 892 companies currently involved in developing products and services.
Regionally, there was a 3.5 percent growth in companies located in North America to 476, or approximately 54 percent of the global total, with 235 companies operating in Europe and Israel, and 122 companies in Asia, representing a significant 18 percent jump so far this year. (See BioWorld Insight, Jan. 22, 2018.)
Business development was also robust, with a number of partnership deals being inked in the period. In September, San Diego-based Fate Therapeutics Inc., which is developing programmed cellular immunotherapies for cancer and immune disorders, entered a collaboration with Osaka, Japan-based Ono Pharmaceutical Co. Ltd. for the joint development and commercialization of two off-the-shelf CAR T-cell product candidates using Fate's induced pluripotent stem cell (iPSC) product platform.
The first iPSC-derived CAR T-cell candidate, the companies report, targets an antigen expressed on certain lymphoblastic leukemias, and Fate retains global responsibility for development and commercialization, with Ono having an option to assume responsibilities in Asia. The second candidate will target an antigen identified by Ono expressed on certain solid tumors.
Fate has enjoyed considerable investor attention and, since the beginning of the year, its share value has doubled (NASDAQ:FATE). The company was able to lever that growth and complete a follow-on offering in September raising gross proceeds of $143.8 million.
Another deal of note involved the strategic collaboration between Bluebird Bio Inc. and privately held Gritstone Oncology Inc. covering cancer cell therapy R&D and commercialization involving 10 tumor-specific targets across multiple tumor types and, in certain cases, T-cell receptors (TCRs) directed to those targets. (See BioWorld, Aug. 24, 2018.)
For its part, Gritstone will employ its EDGE artificial intelligence platform to analyze tumor types and enhance patient selection for cell therapy platforms established by Bluebird, which will handle development, manufacturing and commercial activities. EDGE enables the prediction of the tumor-specific neoantigens, or TSNAs, present on a patient's tumor cells from a routine tumor biopsy. The company exploits that technology to develop and manufacture immunotherapies using TSNAs to drive the immune system to attack and destroy tumors.
Gritstone received $20 million up front and another $10 million in a series C preferred equity investment, together with downstream potential development, regulatory and commercial milestones and tiered royalties on certain commercial products.
A new strategic collaboration between Gilead Sciences Inc. and privately held Precision Biosciences Inc. will focus on developing therapies targeting the in vivo elimination of hepatitis B virus with Precision's Arcus genome editing technology. Precision is eligible for milestone payments of up to $445 million under the terms of the deal and, if successful, could see tiered royalties on sales reaching the midteens. (See BioWorld, Sept. 13, 2018.)
A potential $1 billion-plus deal was signed by Immatics Biotechnologies GmbH for a three-product immuno-oncology research collaboration and license agreement with Genmab A/S. The company pocketed $54 million up front and could earn up to $1.65 billion more in development, regulatory and commercial milestones. The companies will pool their respective capabilities in cancer target discovery, TCR engineering and antibody engineering to develop bispecific protein-based therapeutics that will target both intracellular tumor-associated peptides (Tumaps) and T cells. (See BioWorld, July 13, 2018.)
The ARM Q3 report pointed to the fact that several companies added to their cell and gene therapy portfolios through acquisitions. South Plainfield, N.J.-based PTC Therapeutics Inc., for example, acquired Agilis Biotherapeutics Inc., a move that brings aboard four programs, including one due for a BLA next year. (See BioWorld, July 23, 2018.)
PTC paid $50 million cash up front and about $150 million in stock and pledged a potential $60 million more if development milestones are met.
Agilis was the first company to gain an FDA orphan drug designation for a gene therapy against Friedreich's ataxia. The company's candidate, AGIL-FA, delivers corrective DNA to specific central nervous system (CNS) cells to restore frataxin protein levels.
Despite the choppiness of the public markets in the quarter, companies in the space had no difficulty in raising capital, helping contribute to the collective $16 billion that was generated in the third quarter of the year, according to BioWorld data.
Public companies were responsible for more than 60 percent of the total raised in the period. Cambridge, Mass.-based Bluebird closed an underwritten public offering of 3.89 million shares of its common stock, including 507,692 shares sold by the underwriters, at $162.50 per share, for total gross proceeds of $632.5 million.
Rockville, Md.-based Regenxbio Inc., which is developing gene therapies, closed an underwritten public offering for total gross proceeds of approximately $201.8 million.
Biotech IPOs were also robust in the quarter, with 17 companies graduating to the public ranks on U.S. exchanges, according to BioWorld. Among them was Rubius Therapeutics Inc., which completed its offering generating gross proceeds of $277.3 million. The company is developing a new class of medicines called red cell therapeutics. (See BioWorld, July 19, 2018.)
The pipeline for regenerative medicine products is robust and continues to grow, with the ARM report identifying 1,003 ongoing clinical trials around the world; that represents a 6 percent increase over the number in clinical testing at the end of 2017. Approximately 57 percent of the products being tested are targeting oncology indications, 7 percent are targeting cardiovascular diseases and about 6 percent are focused on CNS disorders.
Of those ongoing studies, 67 percent have been advanced to the mid- and late stages of testing. ARM notes that there are 93 products in phase III testing, comprising 33 gene therapies, 15 gene-modified cell therapies, 33 cell therapies and 12 in tissue engineering.
Editor's note: The second part of this feature will examine some of the promising compounds in clinical development.