Shares of NewLink Genetics are higher ahead of the tomorrow’s presentation at the American Association for Cancer Research’s annua; meeting. Results of a Phase II study of NLG207 combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer has been posted online. The conclusion reads, “NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian cancer including those who have become resistant to platinum therapy. AE profile of this combination is consistent with that seen for paclitaxel as a single agent except for cystitis, hematuria and UTI. It was well-tolerated in combination with weekly paclitaxel in heavily pre-treated patients. NLG207 warrants further investigation in combination therapy regimens for recurrent ovarian, fallopian tube or primary peritoneal cancer, particularly in platinum resistant patients.” Shares of NewLink Genetics are up 9%, or 18c, to $2.11 in afternoon trading.
Monday, April 1, 2019
CareDx CEO says company preparing for more competition
CareDx (CDNA), a molecular diagnostics company focused on the discovery, development and commercialization of diagnostic solutions for transplant recipients, joined The Fly for an exclusive interview. In the interview, CareDx CEO Peter Maag discussed competition and the company’s lawsuit against Natera (NTRA): “Natera is trying to cut corners in bringing their solution to the market. We have worked for 7/8 years to build and make this technology available to transplant patients. And now, I think they’re trying to adopt a fast follower strategy. I think it’s very important to realize that CareDx has relevant IP in the state and that we have established relationships with transplant centers. We’re making sure that we are linking ourselves with these 250 transplant centers in the country, being part of their workflow and caring for patients versus being a company that says, ‘oh I have one more test and I can do that as well.’ This is very critical as we are preparing for more competition in a market, in heart transplant, where we used to be the only company and now there might be other companies coming in the future. So, we are embracing competition.” “Meet the Company” is The Fly’s recurring series of exclusive short interviews with Executive Officers to offer a deeper look inside the company. https://thefly.com/landingPageNews.php?id=2886949
Turning Point Kinase Inhibitors Potent v. Targeted Oncogene Drivers, Mutations
Turning Point Therapeutics, Inc., a clinical-stage precision oncology company designing and developing novel drugs to address treatment resistance, presented data from four studies at AACR 2019, highlighting potent activity of its kinase inhibitors, including repotrectinib against targeted oncogene drivers and many of their resistance mutations, and TPX-0022, a novel MET/CSF1R/SRC inhibitor.
Two studies highlighted the higher potency of repotrectinib as compared to other proxy investigational and the currently approved ROS1 and TRK tyrosine kinase inhibitors (TKIs), Xalkori and Vitrakvi, against fusion ROS1s, wildtype TRK, and many resistance mutations, including solvent front, gatekeeper, and compound mutations.
Alexander Drilon, M.D., Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and an investigator in the Phase 1 portion of the ongoing TRIDENT-1 study of repotrectinib, said, “As physicians adopt next-generation sequencing to identify genomic alterations in different cancers, there is an increased need for precision therapies that target specific oncogenes, such as TRK and ROS1. Repotrectinib was found to have 10-fold or higher increased potency when compared to proxy investigational and the currently approved TRK inhibitors against wildtype (WT) TRK fusions and solvent-front mutations. The findings — while early — are significant and warrant continued clinical study.”
Data for TPX-0022, a novel, internally developed MET/CSF1R/SRC inhibitor approaching IND submission in 1H 2019, were presented for the first time at the conference. TPX-0022 was designed to target MET-driven tumor cells, but also modulate the tumor microenvironment by inhibition of CSF1R. This dual modulation has demonstrated significant tumor growth inhibition in preclinical models.
The data shown in two posters highlighted the ability of TPX-0022 to potently inhibit MET-driven cancer cells and the associated signaling of known cancer pathways, inhibiting tumor growth and reducing tumor associated macrophages. This dual mechanism of action showed tumor regression and growth inhibition in multiple xenograft tumor models harboring METamplification or MET exon 14 skipping mutations.
OncoSec Gets EMA Advanced Therapy Medicinal Tag for Melanoma Candidate
OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing novel cancer immunotherapies, announced today that it has received Advanced Therapy Medicinal Product (ATMP) classification for the Company’s lead investigational product candidate, TAVO™ (DNA plasmid vector expressing IL-12 gene), as a potential treatment for refractory metastatic melanoma from the European Medicines Agency (EMA).
Only innovative investigational product candidates that are based on gene, tissue or cell therapy are qualified for classification as advanced therapy medicinal products. The classification of TAVO as an ATMP is a significant step toward its potential accelerated approval in Europe. The ATMP classification qualifies TAVO to take advantage of a specific EMA regulatory framework designed to facilitate the accelerated review, approval, and access to innovative products in the European market. Further, OncoSec intends to avail itself of the numerous benefits and incentives for medicinal products undergoing clinical testing and marketing approval processes in Europe. Such incentives include fee reductions and exemptions in pre- and post-marketing authorization phases; administrative, procedural and scientific advice and eligibility for funding.
“The ATMP designation confirms TAVO as an innovative gene therapy potentially offering a groundbreaking new opportunity for the treatment of refractory metastatic melanoma,” said Robert Ashworth, PhD, Senior Vice President of Regulatory and Quality at OncoSec.
“Similar to TAVO’s existing FDA Fast Track Designation in the United States, the ATMP designation allows OncoSec to take advantage of a specific European regulatory framework designed to facilitate the accelerated review and approval of TAVO in the European market,” said Daniel J. O’Connor, OncoSec’s President and CEO. “Obtaining this important designation delivers on one of OncoSec’s key objectives for 2019.”
The Committee for Advanced Therapies (CAT) at the EMA is responsible for classifying and assessing the quality, safety and efficacy of products designated as ATMP. The CAT is a multidisciplinary committee of the best available experts in Europe. The main responsibility of the CAT is to prepare a draft opinion on each ATMP application submitted to the EMA before the Committee for Medicinal Products for Human Use (CHMP) adopts a final opinion on granting a marketing authorization for the product. During drug development, CAT also reviews and certifies the acceptability of quality and non-clinical data.
In February 2017, the U.S. Food and Drug Administration (FDA) designated the investigation of OncoSec’s TAVO in combination with KEYTRUDA® (pembrolizumab) to stop or cause the regression of the tumor of patients with Stage III/IV melanoma who are progressing on either KEYTRUDA® (pembrolizumab) or OPDIVO® (nivolumab) treatment as a Fast Track Development Program. Fast Track designation is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. A drug that receives Fast Track designation is eligible for Accelerated Approval if relevant criteria are met.
Ironwood Spins off Cyclerion With 5 Orphan Disease Compounds
In late-February, Cambridge, Mass.-based Ironwood Pharmaceuticals announced it had entered into a private placement deal of up to $175 million that would be used to support its spinoff of Cyclerion Therapeutics. Today, Cyclerion has been launched on the second floor of a 200,000-square-foot, 3-story space on Binney Street, in Cambridge.
After the separation, no ongoing funding between Ironwood and Cyclerion is expected aside from some shorter-term transition expenses and other services. Ironwood isn’t expected to retain equity in the new company and did not invest in the private placement.
Cyclerion plans to utilize the power of sGC pharmacology to discover, develop and commercialize breakthrough treatments for serious and orphan diseases. It has a portfolio of five differentiated sGC stimulator programs each designed for unique target tissues.
These programs all have milestones expected this year. They include olinciguat in Phase II development for sickle cell disease, praliciquat in Phase II for heart failure with preserved ejection fraction (HFpEF) and for diabetic nephropathy. IW-6463 is in Phase I for serious and orphan central nervous system diseases, and two late-stage discovery programs target serious liver and lung diseases.
At the time of the private placement, Peter Hecht, Ironwood’s then chief executive officer and expected chief executive of Cyclerion, stated, “We are grateful for the strong support from the outstanding and experienced group of investors who are participating in this financing. We look forward to launching Cyclerion and Ironwood less than one year since our initial announcement of the separation, and to advancing our efforts to create innovative new medicines for patients and generate value for our shareholders.”
Ironwood was founded in 1998 and developed Linzess to treat irritable bowel syndrome with constipation, which launched commercially in 2012 with Allergan. Ironwood has two experimental compounds in mid- and late-stage clinical trials for gastrointestinal disorders.
Mark Mallon, who recently took over as Ironwood’s chief executive officer after 24 years at AstraZeneca, told the Boston Globe, “These two companies are particularly well-positioned, post the spin[off], to really do great things. It was the right strategy at the right time.”
As part of the tax-free spinoff, today Ironwood shareholders will receive one share of Cyclerion stock for every 10 shares of Ironwood stock. Cyclerion also begins trading on the Nasdaq Tuesday.
David Nierengarten, an analyst for Wedbush Securities, wrote in a note that the spinoff was a “reasonable strategy” that leverages the two executives’ strengths. In the case of Hecht, research and development; in the case of Mallon, marketing gastrointestinal franchises.
Per the Boston Globe, “Ironwood announced it would split into two independent publicly traded firms last May, three weeks after it took the unusual step of telling shareholders that an activist investor, Alex Denner, was seeking to join its board.”
Denner is the chief investment officer of a Greenwich, Conn.-based hedge fund, Sarissa Capital Management. Prior to launching Sarissa in 2012, Denner ran biotech investments for Carl Icahn. In interviews with the Boston Globe last spring, Denner indicated he wasn’t pleased with Ironwood’s stock price and didn’t like the way the company launched drugs for common diseases like irritable bowel disease while also developing drugs for rare diseases. He did, however, endorse the spinoff.
Hecht, on his part, indicates he had been discussing the idea of splitting up the company for several years and that Denner was “not a key protagonist in the story.” He instead, gives credit to other investors.
The spinoff also marks a much smaller company for Ironwood. At year-end 2017, Ironwood had 730 staffers, but under its new identity, will have 330. About 140 moved to Cyclerion and about 260 jobs were eliminated in January 2018. Most of those job cuts came from a decision to stop marketing lesinurad, a drug for gout it had licensed from AstraZeneca in 2016. Sales were disappointing.
Astellas’ Xospata Provides Strong OS Benefits in Phase III Trial
Astellas’ blood cancer drug Xospata continues to demonstrate impressive results in the acute myeloid leukemia setting. During a presentation at the American Association for Cancer Research meeting over the weekend, Astellas touted new overall survival data for Xospata.
Japan-based Astellas said the Phase III ADMIRAL trial comparing Xospata (gilteritinib) to salvage chemotherapy in adult patients with relapsed or refractory AML with an FLT3 mutation showed that patients treated with Xospata had “significantly longer” overall survival data than those who only received standard salvage chemotherapy. The Phase III ADMIRAL trial was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The 371-patient trial randomized the subjects in a 2:1 ratio to receive Xospata or salvage chemotherapy. Results from the ADMIRAL trial show the median OS for patients who received Xospata was 9.3 months compared to 5.6 months for patients who received salvage chemotherapy. One-year survival rates were 37 percent for patients who received Xospata compared to 17 percent for patients who received salvage chemotherapy.
“Overall survival is a benchmark clinicians often rely upon to select treatments for patients with life-threatening diseases,” Andrew Krivoshik, senior vice president and Oncology Therapeutic Area Head at Astellas Pharma told BioSpace over the weekend. “The positive data presented at AACR underscore the important role that Xospata may play in the treatment of patients with relapsed/refractory FLT3mut+ AML.”
The U.S. Food and Drug Administration approved Xospata in November for this AML indication, a rare and life-threatening disease mutation. It was the first FLT3-targeting therapy to be approved for these patients. Of the 19,000 people in the United States who are estimated to be diagnosed with AML this year, nearly 40 percent will have an FLT3 mutation. The Astellas drug has shown itself to be effective against two FLT3 mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).
Alexander Perl, an associate professor of Hematology-Oncology in Penn’s Perelman School of Medicine and an Astellas trial researcher, said the findings of the Phase III ADMIRAL trial are encouraging for this patient population. Perl said patients with relapsed/refractory FLT3 mutation-positive AML generally have a poor prognosis and short survival.
“Until just recently, they had few treatment options. These findings change the treatment paradigm for this patient population,” Perl said in a statement.
The most common treatment-emergent adverse events that occurred in more than 10 percent of patients included anemia, increased alanine aminotransferase, increased aspartate aminotransferase, febrile neutropenia, thrombocytopenia, constipation, fatigue, nausea, cough, headache and diarrhea.
Astellas is currently investigating Xospata in various FLT3 mutation-positive AML patient populations through several Phase III trials. In addition to its approval in the United States, Xospata has also been cleared for use in Japan. A Marketing Authorization Application was submitted in Europe in February.
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