An exciting inflection point for regenerative medicine sector

Targeting oncology

In terms of indications, 45 percent of the products being tested are targeting oncology indications, 11 percent are targeting cardiovascular diseases and about 6 percent are focused on CNS disorders.

That activity translates into “an exciting near-term future for regenerative medicine given the number of pivotal trials that are ongoing,” Preti observed.

There are a number of therapeutic platform enabling technologies supporting the product development, including the expanding field of cell-based immunotherapies, synthetic gene delivery vehicles, genome editing and next-generation gene expression constructs.

He also highlighted just how rapidly the sector is advancing by referencing the gene therapy, gene-modified cell therapy and genome editing areas of the industry. There are a significant number of companies that are active in that space – and some have achieved major milestones. In 2016, GlaxoSmithKline plc received European approval for Strimvelis (GSK 2696273), an ex vivo stem cell gene therapy, for ADA-SCID (severe combined immunodeficiency due to adenosine deaminase deficiency). Strimvelis consists of autologous CD34-positive cells that are transduced with a normal copy of the adenosine deaminase gene.

Spark Therapeutics Inc. reported positive data from the continuation of the phase III trial of voretigene neparvovec (formerly SPK-RPE65), its most advanced product candidate for the potential treatment of inherited retinal disease caused by mutations in the RPE65 gene.

In December, Kite Pharma Inc. began a rolling submission with the FDA of a biologics license application for KTE-C19 as a treatment for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant. A pivotal ZUMA-1 study supporting this submission enrolled patients with chemorefractory diffuse large B-cell lymphoma, transformed follicular lymphoma and primary mediastinal B-cell lymphoma, three subtypes of aggressive NHL. The company said it expected to complete its submission by the end of the first quarter.

Also in December the FDA gave the green light to Vericel Corp.’s MACI (autologous cultured chondrocytes on porcine collagen membrane) to repair symptomatic single or multiple full-thickness cartilage defects of the knee, with or without bone involvement, in adults.

Corporate partnerships

The sector continued to be extremely active in business development during the year with a host of corporate partnerships being signed. Among those were Biogen Inc’s broad collaboration and alliance with the University of Pennsylvania to advance gene therapy and gene editing technologies. The research and translational development collaboration will primarily focus on the development of therapeutic approaches that target the eye, skeletal muscle and the CNS. Another important aspect will be the validation of next-generation gene transfer technology using adeno-associated virus (AAV) gene delivery vectors. Under the terms of the agreement, UPenn may receive up to $2 billion in research funding, options and milestone payments, with Biogen making an up-front payment of $20 million with an additional $62.5 million committed to fund R&D costs extending over the next three to five years in seven distinct preclinical research and development programs.

Pfizer Inc. partnered with Bamboo Therapeutics Inc., paying $150 million up front and committing to 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 Pfizer. (See BioWorld Today, Aug. 2, 2017.)

The acquisition provides Pfizer with access to Bamboo’s vector design technologies, including chimeric rAAV, self-complementary and dual glycan receptor rAAV. The technologies are designed to improve the efficiency of delivering therapeutic genes into host cells. Medigene AG signed an alliance with Bluebird Bio Inc. to develop T-cell receptor-based immunotherapies, in which it is getting $15 million up front plus more than $1 billion in potential milestone payments covering preclinical and clinical development, regulatory approval and product sales. The deal covers four TCR-based therapies across several undisclosed cancer indications. Medigene will also receive research funding over the three-to-four year term of its active R&D collaboration with Bluebird Bio and tiered royalties on eventual sales, ranging from single to double digits.

Positive fundraising

From a financial perspective, Preti pointed out that the regenerative medicine sector has received sustained investor support. As a result, it performed very well in what was a down year for the industry as a whole. In total, the sector generated $5.3 billion in 2015. Although that total was about half of the $10.3 billion raised by regenerative medicine and advanced therapies companies in 2015, it still was a substantial haul. Up-front payments from corporate partnerships and M&A transactions contributed about $1.7 billion of the total raised in 2016.

There were nine companies in the sector that collectively raised $577 million from IPOs. Topping the list in terms of money raised was Intellia Therapeutics Inc., a gene editing startup that raised $124 million from its IPO in May. Editas Medicine Inc., which is also developing gene editing therapies based on CRISPR technology, scored $104 million from its IPO.

Gene therapy specialist Audentes Therapeutics Inc., which is developing treatments for X-linked myotubular myopathy, raised $85 million from its IPO.

Summing up, Preti said the sector continues to exhibit momentum with a clinical pipeline that is robust and growing. It is poised to deliver on a number of late-stage data events this year and beyond.

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