SAN FRANCISCO – The superlatives were flowing for the continuing progress of the regenerative medicine sector at the Alliance for Regenerative Medicine's (ARM) state of the industry briefing on cell and gene therapies presented at the recent Biotech Showcase 2018 conference. Speaking to a packed audience of pharma and biotech company delegates as well as industry analysts and media, Robert Preti, chairman of ARM and president and CEO of Hitachi Chemical Advanced Therapeutics Solutions, proclaimed that 2017 represented a truly breakthrough year for the sector in his opening remarks of the event.

"What a truly tremendous year," he said. "This update will be like no other from the previous seven annual industry updates."

Global growth

Preti noted that the size of the industry continues to expand, with growth occurring in all major markets.

At the end of 2017, ARM had identified an approximate 9 percent year-over-year growth in the number of regenerative medicine companies in operation around the world. In total, 854 are involved in gene and cell therapies – up from the 780 in 2016 and 672 at the end of 2015. (See BioWorld Insight, Jan. 17, 2017.)

Regionally, there was an 18 percent annual growth in companies located in North America to 460, or approximately 54 percent of the global total, with 234 companies operating in Europe and Israel (up 9 percent over the 2016 total), and 122 companies in Asia, the same number as was reported in 2016.

In concluding his remarks, Preti said the future looks bright for the sector, citing a November 2017 Massachusetts Institute of Technology NEWDIGS (NEW Drug Development ParadIGmS) Initiative research brief, which estimated that about 40 gene therapies will be approved by the end of 2022 based on the products that are currently in the pipeline.

Drawing from the results from the alliance's industry analysis, Janet Lambert, CEO, of ARM, reiterated that 2017 had been an exciting year thanks to the FDA approval of three cell/gene therapies: Spark Therapeutics Inc.'s Luxturna (voretigene neparvovec-rzyl) gene therapy for biallelic RPE65 mutation-associated retinal dystrophy, an ultra-rare progressive disease that leads to vision loss and may cause blindness; Gilead Science Inc./Kite Pharma Inc.'s Yescarta (axicabtagene ciloleucel), the chimeric antigen receptor (CAR) T-cell therapy approved to treat adults with relapsed or refractory large B-cell lymphoma; and Novartis AG's Kymriah (tisagenlecleucel) CAR T immunotherapy for B-cell acute lymphoblastic leukemia. (See BioWorld, Oct. 20, 2017, and Dec. 20, 2017.)

The companies of all three products have filed for registration in Europe, where in December, Tigenix NV received European approval for the first allogeneic adipose-derived stem cell therapy, Alofisel (Cx-601, darvadstrocel), in the treatment of complex anal fistulas caused by Crohn's disease, Lambert noted.

Tigenix received U.S. orphan drug designation for Cx-601 in October and it said it intends to apply for the FDA's new regenerative medicine advanced therapy (RMAT) designation.

"We are thrilled about the implementation of the RMAT designation by the FDA, which forms part of a supportive environment for our industry," Lambert said.

Since its implementation, the FDA reports that 16 products have received the RMAT designation from the Office of Tissues and Advanced Therapies.

Robust pipeline

The pipeline for regenerative medicine products is robust and continues to grow, Lambert explained. ARM's report identified 946 ongoing clinical trials around the world; that represents an 18 percent increase over the number in clinical testing at the end of 2016. Approximately 53 percent of the products being tested are targeting oncology indications, 10 percent are targeting cardiovascular diseases and about 6 percent are focused on CNS disorders.

Of those ongoing studies, 66 percent have advanced to the mid- and late stages. ARM noted that there are 82 products in phase III testing comprising 30 gene therapies, nine gene modified cell therapies, 38 cell therapies and five in tissue engineering.

A number of the products in late-stage testing will have data readouts this year or early in 2019. Among them include Cambridge, Mass.-based Bluebird Bio Inc., whose ongoing Northstar-2 (HGB-207) phase III study of its gene therapy lentiglobin drug product in patients with transfusion-dependent beta-thalassemia (TDT) is due to report midyear.

In October, Brainstorm Cell Therapeutics Inc., of Hackensack, N.J., enrolled its first patients in the phase III trial of stem cell therapy Nurown in amyotrophic lateral sclerosis (ALS). That study is set to enroll about 200 patients and will measure the ALSFR-S score responder analysis as the primary endpoint. Top-line data are expected in 2019.

In addition, Australian cell therapy developer Mesoblast Ltd. is progressing it phase III trials with its allogeneic mesenchymal precursor cell therapy to treat chronic low back pain due to intervertebral disc degeneration.

Pharma takes notice

Not surprisingly, the growth of the sector has attracted the attention of large biopharmaceutical companies who were very active in business development during the past year with a host of corporate partnerships being signed.

In May, Pfizer Inc. signed a deal with Sangamo Therapeutics Inc. for its hemophilia A program, which could be worth more than $500 million for gene therapy SB-525 as well as potentially other candidates. The collaboration and license agreement will develop and commercialize SB-525, one of Sangamo's four lead candidates. (See BioWorld Today, May 12, 2017.)

Sangamo received a $70 million up-front payment and will be responsible for conducting the SB-525 phase I/II study, along with certain manufacturing activities. After that, Pfizer will be operationally and financially responsible for further research, development, manufacturing and commercialization work for the product.

Pfizer is investing heavily in gene therapy and in 2016 it partnered with Bamboo Therapeutics Inc., paying $150 million up front and potential milestone payments of up to $495 million. Bamboo, which has preclinical neuromuscular and central nervous system programs from its recombinant AAV (rAAV) vector technology and a fully operational phase I/II gene therapy manufacturing facility, will operate as a wholly owned subsidiary of the big pharma. (See BioWorld Today, Aug. 2, 2016.)

At the end of the year, Nanjing-based Legend Biotechnology Corp. announced it had partnered with Janssen Biotech Inc., a subsidiary of Johnson & Johnson, to develop in CAR-B38M, a promising CAR T-cell therapy for multiple myeloma that targets B-cell maturation antigen (BCMA). It received $350 million in cash with future undisclosed milestones earmarked in the deal.

Gilead's $11.9 billion acquisition of Kite also helped define the year for regenerative medicine and boost the amount disclosed in M&A transactions to $13.5 billion.

Record fundraising period

From a financial perspective, Lambert said the regenerative medicine sector has received record levels of investor support. In total, $7.5 billion was raised by companies in 2017, almost double the $4.2 billion that was raised a year earlier.

Follow-on financings by regenerative medicine and gene therapy companies generated about $4 billion. Notable transactions included Bluebird Bio, which raised more than $1 billion from two transactions: $460 million in June and $651 million in December. Philadelphia–based Spark successfully completed a follow-on offering, which raised more than $400 million. Private companies in the space also received unprecedented support, with $1.3 billion in venture capital being invested in 2017.

Headline deals included Rubius Therapeutics Inc., which raised $120 million in an oversubscribed round to build out the company and advance its lead red-cell therapeutics candidates into the clinic. (See BioWorld, June 21, 2017.)

The company said it has developed the technology to grow, genetically engineer and mature long-circulating red cell therapeutics, which will provide clinical benefits to a wide range of patients across multiple therapeutic areas. The allogeneic, off-the-shelf products offer the additional advantage of extended stability and storage to allow for rapid, universal access.

In December, Semma Therapeutics Inc. raised $114 million in a series B financing to help support proof-of-concept studies of its stem cell-derived beta cells, a potential therapy for people living with type 1 diabetes. The company is planning to file an IND for the program while also exploring additional applications for its technologies.

Also in December, Orchard Therapeutics Ltd. raised an oversubscribed £85 million (US$113.5 million) series B round, which will be used to fund the commercialization of rare disease gene therapy programs in-licensed from academic labs.

In the near term, the company will be working on the global launch of its lead product, OTL-101, an autologous ex vivo lentiviral vector gene therapy for the treatment of the severe inherited disorder adenosine deaminase severe combined immunodeficiency. The therapy has FDA breakthrough designation and is in a late-stage trial funded by the California Institute for Regenerative Medicine.

Plenty of work ahead

Summing up, Lambert said the sector is maturing with growing public recognition and enthusiasm. "There is a very supportive regulatory environment both in the U.S. and in Europe," she added.

Going forward the continued success of regenerative medicine will require good policy frameworks, and ARM intends to work on developing strategies to remove or mitigate barriers for public and private payers both in the U.S. and in key EU countries.

Industrialization and manufacturing will also be a priority this year for the alliance as it aims to reduce the technical and regulatory barriers related to scale up in the production regenerative medicine therapies.