SAN FRANCISCO – In delivering the Alliance for Regenerative Medicine's (ARM) 2016 state of the industry briefing at the Biotech Showcase event, chair of the international advocacy organization representing the regenerative medicine and advanced therapies (RM/AT) community, Edward Lanphier, said 2015 had been a great year for the sector, exemplified by excellent clinical data readouts that have helped attract significant investments and big pharma validation through major partnerships.

The sector continues to evolve and grow and ARM has identified 672-plus companies, including those involved in gene and cell therapies, around the world that are active in the space. That represents a 30 percent increase from the 517 companies identified in 2014. (See BioWorld Insight, Jan. 20, 2015.)

Approximately 52 percent, or 349 companies, are located in U.S., with 185 (27 percent) in Europe and 112 (17 percent) in Asia. Lanphier was particularly enthusiastic about the growing value creation in the sector through the approval of 20 new products and expanding number of ongoing clinical trials. In fact, since the year-earlier report there has been an almost doubling of clinical trial activity, with more than 631 trials identified in 2015; 70 percent of those have progressed to the phase II and phase III stages. More than 40 percent of those are targeting oncology indications.

Taking off

There is no doubt that oncology trials "have really taken off," Lanphier noted, "particularly with the explosion in cell-based immuno-oncology."

CAR T and other cell-based therapies are being advanced by a host of major companies and research institutions. For example, at the American Society of Hematology (ASH) meeting in December, Novartis AG presented the latest findings from an ongoing phase II study of CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy, which further support its potential in the treatment of children and young adults with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). The study found that 55 of 59 patients (93 percent) experienced complete remissions (CR) with CTL019. Overall survival was 79 percent at 12 months.

Juno Therapeutics Inc. also reported clinical data from separate trials for CAR T cell product candidates, JCAR015 and JCAR014, demonstrating encouraging clinical responses in patients with r/r ALL. The JCAR014 data showed the addition of fludarabine to cyclophosphamide-based lymphodepletion improves CAR T-cell expansion, persistence and disease-free survival in r/r B-cell adult ALL patients treated with a defined cell product.

In the area of gene therapy there are also a number of mature programs in progress. Lanphier referenced Uniqure NV, which reported that four of five patients suffering from severe or moderately severe hemophilia B have been able to discontinue prophylaxis with recombinant factor IX, following treatment with its AMT-060 gene therapy, and Spark Therapeutics Inc.'s phase III top-line data with its compound, SPK-RPE65, for blindness-causing, RPE65-mediated, inherited retinal dystrophies has impressed. That trial demonstrated a highly statistically significant improvement in the intervention group compared to the control group in the primary endpoint, the change in bilateral mobility testing (MT) between baseline and one year. The first two secondary endpoints – full-field light sensitivity threshold testing and MT for the assigned first eye – also showed highly statistically significant improvement. (See BioWorld Today, Jan. 8, 2016, Oct.6, 2015.)

Separately, at the J.P. Morgan Healthcare conference, Spark outlined its comprehensive three-year vision for expanding the company's portfolio through 2018 and launching its first commercial product in 2017.

In all, the Philadelphia-based company will advance a total of 10 total programs across three therapeutic franchises by 2018, including one commercially approved therapy, two in pivotal-stage trials and at least seven additional programs in clinical proof-of-concept trials.

Those are just a few examples where significant value is being created, and it bodes well for a number of new approvals to come in the not too distant future, Lanphier explained.

Value inflection points

Those value inflection points served to drive the establishment of key corporate partnerships that were inked during the year.

For example, Crispr Therapeutics AG announced in December that Leverkusen, Germany-based Bayer AG is investing a total of $335 million in order to establish a long-term alliance that will leverage promising CRISPR-Cas9 gene-editing technology. The deal followed the Basel, Switzerland-based company inking a four-year collaboration with Vertex Pharmaceuticals Inc. in late October to discover and develop treatments for genetic diseases, including cystic fibrosis and sickle cell disease. (See BioWorld Today, Dec. 22, 2015, and Oct. 27, 2015.)

In April, Uniqure and Bristol-Myers Squibb Co. signed a potential $2 billion-plus deal to develop treatments for cardiovascular diseases. At the heart of that agreement is a gene therapy for congestive heart failure, in which it is proposed a one-off treatment would restore the heart's ability to synthesize S100A1, a calcium-binding protein which acts as a master regulator of myocardial function. In addition, BMS will nominate nine other targets. (See BioWorld Today, April 7, 2015.)

Those deals are an important validation by big pharma and represent the interest they are exhibiting in the technology, Lanphier said.

They are also providing confidence for investors, and the statistics bear that out. In terms of fundraising, 2015 was another great year, with $10.3 billion raised by regenerative medicine and advanced therapies companies, representing a year-over-year growth of 112 percent. Of that amount, M&As, follow-on offerings and up-front payments from corporate partnerships contributed a combined $7 billion.

Companies in the field collectively raised almost $1.7 billion from IPOs. There were seven companies that successfully generated more than $100 million from their IPOs.

Topping the list in terms of money raised was Cardiff-by-the-sea, Calif.-based Nantkwest Inc., riding a wave of investor passion for immuno-oncology to gross $238 million. The company is developing several types of natural killer (NK) cells. Activated NKs (aNKs) make up a cell-based "off-the-shelf" treatment that's been tested in phase I trials. Unlike normal NK cells, Nantkwest's do not express killer inhibitory receptors, which are often exploited by diseased cells to escape the work done by NK cells. The aNK cells also are said to carry a bigger payload of granzyme and perforin-containing granules, so they can aim more of the lethal enzymes at multiple targets. The company also is working on high-affinity NKs, so named because they express high-affinity CD17, which mean they could ramp up therapeutic efficacy of antibodies targeting cancer cells. (See BioWorld Today, July 29, 2015.)

Not far behind was the Cellectis SA IPO, which raised $228 million to advance its CAR T pipeline.

Enthusiasm for gene therapy saw Spark complete an upsized IPO to bank $185 million in February to support its lead candidate, SPK-RPE65, as well as a follow-on candidate targeting choroideremia and other programs that join a growing list of treatments addressing disease at the genetic level.

Also in the gene therapy space, Voyager Therapeutics Inc. graduated to the public ranks thanks to an $80.5 million offering to help movie along a partnered gene therapy Parkinson's disease candidate that has reached the phase I stage.

Building on that momentum early in 2016, Editas Medicine Inc., which is developing gene-editing therapies based on CRISPR technology, filed to raise up to $100 million in an IPO; and gene therapy specialist Audentes Therapeutics Inc., which is developing treatments for X-linked myotubular myopathy, filed to raise up to $86 million from an IPO.

As good as 2015 was for the sector, Lanphier emphasized that the organization needs to continue to play an important leadership role in communicating the value that companies are creating in bringing effective new medicines to patients. In parallel, it will continue to work on global reimbursement issues, payment, coverage and coding policies for RM/AT products.

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