ASH Roundup: Immunotherapy Stars, Gene Therapy Leaps Ahead

Xconomy San Francisco — 

Cancer immunotherapy and gene therapy grabbed many of the headlines from this past weekend’s American Society of Hematology meeting in San Francisco, and a number of the companies those fields look primed to cash in with big offerings in the coming weeks.

Two such companies are already prepping to do so: Juno Therapeutics of Seattle, a developer of cellular immunotherapies, revealed Wednesday that it’s shooting to raise as much as $191 million in its upcoming IPO, which looks to be the biggest biotech offering of the year. Juno is expected to price next week.

Houston’s Bellicum Pharmaceuticals, another T-cell therapy player, set a range for its IPO Tuesday, saying it aims to sell 6.25 million shares at $15-$17 apiece. It also could begin trading on the Nasdaq next week.

Others have already cashed in. Agios Pharmaceuticals (NASDAQ: AGIO), for instance, just raised a whopping $220 million last night, selling almost 2 million shares at $110.75 apiece. It’s the latest step in a big run for Agios, which, for reference, was worth $18 a share when it went public a year ago.

The raise comes after a series of recent data updates from Agios. Most recently, at ASH, Agios showed it’s already on the precipice of a pivotal trial—the last required before filing for FDA approval—just two years after dosing the first patient in its first trial. Its acute myeloid leukemia drug, AG-221, continues to maintain a roughly 56 percent overall response rate as more patients participate in the trial; those responses, in some cases, have lasted as long as eight months. Agios also gave investors the first look at a drug called AG-348, for a rare, inherited form of anemia.

It wouldn’t be surprising, meanwhile, to see Bluebird Bio (NASDAQ: BLUE) soon tap Wall Street for cash as well. Bluebird showed at ASH that the first four beta-thalassemia patients given its gene therapy are free of the frequent blood transfusions they would otherwise require to fend off anemia. The data are a leap ahead for the gene therapy field, which has undergone a renaissance over the past few years. They’ve also nearly doubled Bluebird’s value since: shares are worth $82.71 apiece post-ASH, up from $48.89 before the meeting.

On the ground at the conference (where the notable number of attendees smoking outside on the San Francisco sidewalks gave an extra layer of meaning to the acronym ASH), we covered discussions of the two main types of cancer immunotherapy: cell-based methods and antibody-based treatments. The cell-based methods, the likes of which are being pursued by Juno, Novartis (via a collaboration with the University of Pennsylvania), Bellicum, Kite Pharma (NASDAQ: KITE), and others, continued to show very promising results in early studies. Kite used that momentum to raise about $188 million in a follow-on offering on Wednesday.

The so-called PD-1 checkpoint inhibitors, meanwhile, proved they just might have a place in treatment regimens for various lymphomas—just not multiple myeloma, a disappointment to some of the experts in attendance.

We also outlined the uphill battle of Sunesis Pharmaceuticals (NASDAQ: SNSS) to gain approval for its leukemia drug, vosaroxin. The drug failed a Phase 3 trial earlier this year; Sunesis contends that certain subgroups of patients in that study had a statistically significant benefit, and will head to the FDA to file for approval of the drug in the first quarter of 2015.

But there was much more that we couldn’t get to from companies around the Xconomy network, from Boston to San Francisco. So we’ve decided to round up some of those tidbits below.

—Bluebird wasn’t the only company to report encouraging beta-thalassemia data at ASH. Shares of Cambridge-based Acceleron Pharma (NASDAQ: XLRN) climbed more than 13 percent Monday after positive results from mid-stage trials of two drugs, sotatercept and luspatercept (formerly ACE-536), for beta-thalassemia and myelodysplastic syndrome (a disease of the bone marrow). Both drugs helped increase patients’ hemoglobin levels and reduce some patients’ transfusion burdens. We profiled Acceleron’s efforts, and its prospective battle with Bluebird, back in July.

—Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY) saw its shares rise five percent following two ASH releases. One highlighted interim Phase 1 data from ALN-AT3, a subcutaneous RNA interference drug for hemophilia and other rare bleeding disorders. Full data from the trial is due in mid-2015. The company also filed an application with U.K. regulators to begin a Phase 1/2 trial for ALN-CC5 in paroxysmal nocturnal hemoglobinuria, the ultra-rare disease treated by eculizumab (Soliris) from Alexion Pharmaceuticals (NASDAQ: ALXN). Assuming Alnylam gets clearance, initial data are expected next year.

Amgen (NASDAQ: AMGN) followed up last week’s FDA approval of the antibody blinatumumab (Blincyto) by releasing long-term survival data for adult patients with acute lymphoblastic leukemia. Of 36 treated, 10 have survived nearly 30 months, and seven of them were relapse-free. Amgen could also report that for multiple myeloma, carfilzomib (Kyprolis) in combination with two other drugs delivered a median progression-free survival of 26.3 months, which bests the previous top figure of 19 months, according to the Mayo Clinic investigator who presented the Phase 3 results.

—One of ASH’s biggest winners: Summit, NJ-based Celgene (NASDAQ: CELG). Several of its partners and equity investments—Agios, Acceleron, and Bluebird—rolled out positive data and saw shares climb. And the so-called PD-1 checkpoint inhibitors disappointed in multiple myeloma, kneecapping a potential threat to Celgene’s franchise.

—French firm Cellectis—which is partnered with New York-based Pfizer (NYSE: PFE)—said it plans to start human trials with its CAR-T immunotherapy platform that does not require a patient’s own T cells as the basis for the treatment. The firm says it has developed an “off the shelf” procedure for manufacturing genetically engineered donor cells; its first trial will include patients with CD19-positive B cell leukemia.

—Cambridge, MA-based Foundation Medicine (NASDAQ: FMI) kept building the case for its FoundationOne Heme, a diagnostic that analyzes the genomic profile of blood cancers. (Its other test, FoundationOne, does the same for solid tumors.) Foundation presented three studies: In a 112-patient study, 96 percent had genetic alterations with “therapeutic relevance”—meaning, a marketed or experimental drug exists that targets those genetic abnormalities. In a second study, 42 of 84 patients with various blood cancers had relevant genetic alterations; 12 of those cases (14 percent) led to a change in the patient’s diagnosis. Foundation added a third study purporting to show that FoundationHeme led to a clinical benefit for patients with relapsed multiple myeloma. The company is conducting studies like these to convince insurers to cover its tests.

—Cambridge-based Epizyme (NASDAQ: EPZM) provided an early look at preclinical data for its third drug, a PRMT5 inhibitor it’s developing with GlaxoSmithKline (NYSE: GSK). Shares trended downward last month after Epizyme released the abstract for a Phase 1 study one of its two lead compounds, EPZ-5676. It updated that data this week as well, revealing one additional partial response to the drug, though investors have shown more interest in another drug—EPZ-6438—that is also in early studies. Epizyme is one of the few recently public, Celgene-partnered biotechs that hasn’t taken off yet. It priced at $15 last year, and currently trades at roughly $21.

—Investigators affiliated with Juno presented or updated five Phase 1 or 1/2 clinical trials. The results included 24 of 27 complete remissions in adults with acute lymphoblastic leukemia after CD19 CAR-T cell therapy; and six of six patients with relapsed/refractory B cell non-Hodgkin’s lymphoma remained alive and in remission at a median follow-up of 9 months after high-dose chemotherapy, autologous stem cell transplant, and CD19 CAR-T cell therapy. Juno lists all five updates here.

—Shares of Newton, MA-based Karyopharm Therapeutics (NASDAQ: KPTI) have roughly doubled in 2014 on the strength of data for the company’s prospective blood cancer drug selinexor. At ASH, Karyopharm released results from a study testing the drug in combination with carfilzomib and dexamethasone, plus more results from a non-Hodgkin’s lymphoma study. Karyopharm’s drugs are supposed to work by keeping the body’s tumor suppressor proteins in the nucleus of cells. You can read more about the approach here.

—Lexington, MA-based Promedior updated numbers from the Phase 2 trial it’s running for PRM-151, a myelofibrosis drug prospect. It’s the latest data from the trial we detailed back in May, and privately-held Promedior said patients’ overall response rate of 43 percent after six months were good enough to move forward.

Alex Lash contributed to this report.