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.

https://www.biospace.com/article/releases/oncosec-announces-advanced-therapy-medicinal-product-classification-from-the-ema-for-tavo-in-refractory-metastatic-melanoma/

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.

https://www.biospace.com/article/ironwood-pharma-announces-spin-off-of-cyclerion-therapeutics/

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.

https://www.biospace.com/article/astellas-xospata-provides-strong-os-benefits-in-phase-iii-trial/

Pfizer Spinout SpringWorks Nabs $125M to Move Candidates to Late-Stage Trials

SpringWorks Therapeutics snagged $125 million in a Series B funding round that will help it accelerate its two late-stage cancer treatments into late-stage trials and toward potential regulatory approval, as well as support the continued expansion of the company’s emerging targeted oncology programs.

The Series B round was backed by stalwart investors in the pharma arena, including ArrowMark Partners, Samsara BioCapital, GlaxoSmithKline and Laurion Capital Management. SpringWorks also saw continued financial support from long-time investors that includes Pfizer, OrbiMed, Bain Capital and LifeArc.

SpringWorks is driving toward potential approval with nirogacestat, a gamma-secretase inhibitor for the treatment of desmoid tumors and PD-0325901, a MEK inhibitor for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas. Both of these late-stage drugs were part of Pfizer’s pipeline when SpringWorks was spun out of that company in 2017. When SpringWorks was launched, the company secured $103 million in a Series A. The company was launched in order to provide some hope for the development of medicines across therapeutic areas where there is an urgent need.

Saqib Islam, SpringWorks chief executive officer, said the latest financing round “underscores the progress” the company has made in advancing its late-stage programs toward pivotal studies.

We are well positioned to continue to execute on our strategy to build a leading rare disease and targeted oncology company that brings promising science to underserved patient communities,” he said in a statement.

In November, SpringWorks received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for PD-0325901. PD-0325901 inhibits MEK, a key signaling protein for cellular survival and proliferation. The investigational therapeutics has been shown to block MEK phosphorylation in clinical biopsies. That blocking causes the cells to die. Neurofibromatosis type 1, or NF1, is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. The company is currently evaluating PD-0325901 as a monotherapy for NF1. But, the company said that given the critical role that the MAPK pathway plays in the growth and proliferation of a large number of tumor types, SpringWorks is also pursuing PD-0325901 in combination with other rational anti-cancer agents across a range of solid tumors. The company anticipates initiating Phase III trial this year. In September, just ahead of the Orphan Drug Designation approval, SpringWorks and Beigene teamed up to develop treatments with PD-0325901. The two companies will pair PD-0325901 with BeiGene’s investigational RAF dimer inhibitor, lifirafenib (BGB-283) in patients with advanced solid tumors.

Also in November, SpringWorks received Fast Track designation from the FDA for nirogacestat, for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. Desmoid tumors are rare and debilitating soft-tissue tumors that can occur in both children and adults. Depending on their size and location, desmoid tumors can cause severe morbidities such as pain, internal bleeding, disfigurement, and limited range-of-motion. In June 2018, the U.S. FDA granted Orphan Drug designation for nirogacestat for the treatment of desmoid tumors. SpringWorks will launch a Phase III trial for nirogacestat this year.

https://www.biospace.com/article/pfizer-spin-out-springworks-nabs-125-million-to-advance-candidates-into-late-stage-trials/

Lonza to Launch H2OBioEV™ Bioactive Functional for Skin Rejuvenation

At in-cosmetics Global 2019, Lonza today launches the newest in its portfolio of bioactives, H2OBioEV™ Bioactive, a multifunctional cosmetic ingredient that revitalizes, rejuvenates and moisturizes skin. In-cosmetics Global 2019 takes place 2-4 April in Paris (FR). Lonza will be at Stand L88.

‘H2OBioEV™ Bioactive moisturizes by replenishing essential humectants, which provide an optimal environment for epidermal proteins to form and maintain a strong barrier, thus restoring a smooth and radiant appearance,’ said Vanessa Arruda, PhD, Global Market Development Manager, Bioactives. ‘It is an evolution in moisturization, to refresh and revitalize skin.’

H2OBioEV™ BioActive is unique because it offers three different biophysical and biochemical approaches to address dry skin from a single ingredient. H2OBioEV™ bioactive rejuvenates skin by:

• Depositing an invisible film that locks moisture in the skin
• Replenishing essential humectants and providing a stabilizing environment for functional skin proteins
• Stimulating the expression of proteins essential to forming and maintaining an optimal skin barrier function

‘The modern consumer has different needs and expectations, which change the way she or he chooses products,’ Dr. Arruda said, referring to a recent Euromonitor survey.¹‘Rather than looking for a specific type of product, consumers are looking for cutting-edge technologies that provide particular functionalities. They recognize five categories of functionality in cosmetic products: rejuvenating, age defying, age reversing, beauty enhancing and imperfection correcting.’

https://www.marketscreener.com/LONZA-GROUP-2956013/news/Lonza-to-Launch-H2OBioEV-trade-Bioactive-Functional-for-Skin-Rejuvenation-at-in-cosmetics-Global-28330604/

Syndax updates findings from melanoma, NSCLC cohorts of ENCORE 601 trial

Syndax Pharmaceuticals (SNDX) announced the presentation of updated findings from the melanoma and non-small cell lung cancer, or NSCLC, cohorts of ENCORE 601, the company’s Phase 1b/2 trial evaluating the efficacy and safety of entinostat, its once-weekly, oral, small molecule, class I HDAC inhibitor, in combination with Keytruda, Merck’s (MRK) anti-PD-1 therapy. The data were presented during oral presentations at the American Association of Cancer Research Annual Meeting. The company presented results from the ENCORE 601 melanoma cohort that enrolled patients whose disease had progressed on or after anti-PD-1 therapy. Of 53 patients treated, a confirmed objective response was observed in 19% of patients per irRECIST criteria, with a clinical benefit rate of 36%. Median duration of response is 13 months. Four responders, all of whom have been on study therapy for over a year, currently remain on treatment. Efficacy results in patients who also received prior Yervoy therapy were consistent with the overall population. The entinostat-pembrolizumab combination was well tolerated with a manageable toxicity profile. Briggs Morrison, M.D., CEO of Syndax, said, “Both indications represent areas of high unmet need and we believe that available data warrant consideration to move the entinostat-pembrolizumab combination into one or more registration trials. As previously communicated, we look forward to determining next steps for the combination program following availability of overall survival results from E2112, our Phase 3 registration trial of entinostat plus exemestane in HR+, HER2- breast cancer, the next interim readout of which is expected in the second quarter of this year.”

https://thefly.com/landingPageNews.php?id=2886830

Bayer resumed with a Hold from Buy at Berenberg

Berenberg transferred coverage of Bayer to analyst Sebastian Bray and downgraded the stock to Hold from an under review designation. The analyst sees downside from legal settlements following the unfavorable glyphosate verdicts. He has a price target of EUR 67 for the shares.

https://thefly.com/landingPageNews.php?id=2886453