Avrobio Hit by Mixed Data from Fabry Disease Gene Therapy Trial

Shares of Cambridge, Mass.-based AVROBIO plunged more than 50 percent on Monday after the company provided an updated look at its gene therapy for Fabry disease that showed promise for the treatment, but also raised some concern for investors.

Citing interim data, Avrobio announced that the first two patients in its Phase I study of its AVR-RD-01 gene therapy treatment continued to “demonstrate AGA enzyme activity above the diagnostic range for classic Fabry disease 18 months and six months.” The company said that the first patient is no longer receiving enzyme replacement therapy. For the patients on the treatment, that was the good news.

Geoff MacKay, president and chief executive officer of Avrobio, touted the results of the treatment for the first two patients.

“We are encouraged by the AGA enzyme activity we are seeing after treatment with AVR-RD-01 in the first two patients with Fabry disease in the Phase 1 study. Both of these patients have AGA activity that remains above the diagnostic range for males with classic Fabry disease, and all patients will continue to be followed for assessment of long-term durable response. We are especially pleased that patient 1 was taken off ERT in mid-July and remains off,” MacKay said in a statement.

Avrobio’s AVR‑RD‑01 is an ex vivo lentiviral gene therapy that is designed as a one-and-done treatment. The therapy works by inserting the GLA gene that encodes functional α‑galactosidase A (AGA), the enzyme that is deficient in Fabry disease. By inserting the GLA gene, the therapy should enable continued AGA production and distribution to tissues and organs. From the initial data, that appears to be happening with AVR‑RD‑01.

However, what has investors concerned is not the results of the AGA enzyme activity, rather it was the fact that four patients saw a drop in vector copy number in peripheral blood. VCN refers to the average number of copies of the lentiviral-vector inserted gene that are integrated into the genome of a cell. While Patient 1 has been taken off the enzyme replacement therapy, his VCN was 0.1. Patient 1 began the study with a VCN of .7. Patient 2 had a VCN of .4 and began with a 1.4. The other two patients also saw a similar decline. That’s what caused share prices to plunge on Monday – wiping out significant gains the company’s stock has made since its initial public offering this past spring when it brought in in $99.7 million.

On Monday, shares fell from Friday’s closing price of $51.80 per share to $25.13.

In separate news, Avrobio announced that it will initiate a Phase I/II trial in Canada to test its lentiviral gene therapy treatment AVR-RD-02 for Gaucher disease. This therapy is designed to permanently integrate the GBA gene that encodes functional glucocerebrosidase, the enzyme that is deficient in Gaucher disease, to enable continuous GBA production and distribution to tissues and organs.

Additionally, the company reported first-patient information from a Phase II trial testing AVR-RD-01, data from the first patient shows AGA plasma enzyme activity was 2.74, but the VVCN was .5.

https://www.biospace.com/article/avrobio-plunges-on-mixed-data-from-fabry-disease-gene-therapy-trial/

Cannabis-Based Med Firms Hope Epidiolex Paves Way for More Approvals

Following the U.S. Drug Enforcement Agency’s rescheduling of GW Pharmaceuticals‘ Epidiolex from a Schedule I to a Schedule V, other cannabis-based drug development companies believe there is momentum for their medications to gain regulatory approval.

In June the U.S. Food and Drug Administration (FDA) approved Epidiolex as a treatment for seizures associated with two rare forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome. The approval of Epidiolex marked the first time the FDA approved a drug that contains a purified drug substance derived from marijuana.

This morning Las Vegas-based GB Sciences, Inc. said the rescheduling and approval of Epidiolex “validates the commercial potential” of the company’s assets. Like U.K.-based GW Pharmaceuticals, GB Sciences is developing cannabinoid therapies for a number of medical conditions. GB’s lead asset is focused on Parkinson’s disease. GB Sciences noted that a significant consequence of the DEA’s rescheduling of Epidiolex, a treatment for a rare form of epilepsy, established that Epidiolex can be distributed to patients through standard pharmaceutical channels. That means, the company said, it will be easier for future cannabis-based medicines to get to patients should they pass regulatory muster.

Despite the DEA’s rescheduling of Epidiolex, other non-FDA-approved CBD preparations remain in Schedule I. That is a sore point for some other CBD drugmakers like GB Sciences.

John Poss, chief executive officer of GB Sciences said GB Sciences is not a “cannabis company that dabbles in science,” rather it is a “biopharmaceutical company that happens to grow cannabis.”

“Although the recent ruling by the DEA is a positive development, it falls short of giving researchers the tools required to rapidly advance cannabis-based drug research and development,” Poss said in a statement.

The hope for GW Pharma’s medication to pave the way for future CBD drugs to gain approval comes days after GB Sciences struck a deal with U.K.-based Catalent Pharma Solutions to provide oral delivery systems, formulation development, and clinical-scale oral dose manufacturing of GB Sciences’ CBD treatments, GBS101, GBS102, and GBS103, for Parkinson’s disease. The company’s assets are complex mixtures containing up to nine cannabinoid-containing complex mixtures. It’s that combination of components that the company said are “more potent than would have been predicted by combining the activity of each individual compound.”

Andrea Small-Howard, chief science officer of GB Sciences, said she was hopeful about the rescheduling of CBD medications to Schedule V, particularly in light of the announcement that Catalent will be formulating the cannabis-based Parkinson’s disease formulations in preparation for the company’s planned exploratory investigational new drug-filing

“This may be the best time in history to be developing cannabis-based medicines,” Small-Howard said in a statement.

To date, GB Sciences said it has filed four patent applications for its cannabinoid-containing complex mixtures for use in four disease categories: neurodegenerative disorders, cardiovascular diseases, inflammatory disorders, and chronic and neuropathic pain. The company said more than 60 potential medical conditions can be addressed by its cannabis-based formulations. CBD is a therapeutic component in about 20 percent of these formulations, the company said. Additionally, the company noted that less than 10 percent of its formulations contain delta-nine tetrahydrocannabinol (THC), the psychoactive component of cannabis.

https://www.biospace.com/article/cannabis-based-drug-companies-hopeful-epidiolex-will-pave-the-way-for-future-approvals/

5-Member GO Therapeutics Inks $195 Million Deal with Roche

GO Therapeutics, headquartered in Cambridge, Mass., signed a licensing deal with Swiss-based Roche to develop antibodies for cancer.

Under the terms of the deal, GO will receive upfront and near-term milestones of $9 million. GO is also eligible for up to $186 million in milestone payments in addition to mid-single-digit to low double-digit royalties on any products that might come out of the agreement.

GO Therapeutics focuses on advances in glycobiology to develop cancer drugs that are both more potent and less toxic. It develops cancer-specific antibodies that can be used as antibody-drug conjugates (ADC), bispecific T-cell engagers and immune-based cell therapies.

“We are excited about this collaboration to develop an innovative immune-redirected therapy to potentially improve the lives of patients suffering from cancer in the future,” said Constantine Theodoropulos, GO Therapeutics’ chief executive officer, in a statement. “GO’s glycoprotein targeting platform opens an exciting class of tumor-specific antigens that can help widen the therapeutic window for cancer therapies such as T-cell bispecific antibodies, CAR-T and ADCs (Antibody Drug Conjugates). Preclinical data show GO’s approach can provide superior specificity in targeting solid tumors over normal tissue and demonstrate clean in-vivo toxicity profiles in the context of potent immunotherapies.”

GO Therapeutics is a tiny company, which makes the size of the deal, relatively small for the industry, look huge in comparison. GO Therapeutics has a staff of five. It is operating out of shared laboratory space at LabCentral in Cambridge.

The company’s technology is designed to be more targeted, which would make the drugs more effective with fewer side effects since they have less impact on healthy cells. The company was founded by Theodoropulos, Hans Wandall and Thayer White.

Theodoropulos has been a business consultant in the life sciences and technology for about 20 years. Before GO, he was founder and president of Base Pair Group, a consultancy. He was head of strategic marketing for EBD Group, a life science partnering events company, where he worked on corporate strategy, product development and marketing. EBD Group was sold to Informa in 2014.

Wandall is the co-director of the center for glycobiology at the University of Copenhagen. His research focuses on the genetics of glycan function, creating epithelial tissue models used to dissect glycan functions in cancer and viral infection.

White earned his doctorate at the University of Washington. He has worked at The Pacific Northwest Research Foundation, The Fred Hutchinson Cancer Research Center, Imre Corporation, The Biomembrane Research Institute, and Cell Therapeutics. He was also the vice president of Research and Development at ZymeQuest.

About a year ago, Salubris Pharma, based in Shenzhen, China, invested $5 million into the company. At the time, Sam Murphy, vice president and head of International Business Development for Salubris, joined GO’s board of directors. “Novel, cancer-specific targets are imperative to widening the therapeutic window for powerful, cutting-edge cancer therapeutic modalities such as T-cell engagement and ADCs that offer tremendous promise for patients around the world,” Murphy stated at the time. “GO Therapeutics has the opportunity to generate significant value by opening an exciting new class of cancer-specific targets that will underpin transformative cancer therapeutics.”

The company expects to add on a couple key staffers, and is contemplating a Series B financing toward the end of the year, based on how close they feel they are to taking any compounds into the clinic.

https://www.biospace.com/article/5-member-go-therapeutics-inks-195-million-deal-with-roche/

Janssen Terminates Collaboration Deal with Aduro Biotech

Janssen Biotech, a Johnson & Johnson company, informed Aduro Biotech that it was terminating its research and license deals related to Aduro’s Listeria treatment for cancers.

The original deal was launched on October 13, 2014 and later amended on November 11, 2015. Under the deal, Aduro gave Janssen an exclusive, worldwide license to research, develop, manufacture, sell and “otherwise exploit” products that have ADU-214, ADU-741 and GVAX Prostate. The terms of the agreement provided Aduro with up to $365 million in upfront license fees and milestone payments, some of which have been paid out. The deal had a potential value of $766 million with high single-digit to low teen royalties. So far, Aduro had received a $30 million upfront payment and a $21 million milestone payment.

Aduro’s LADD platform uses live-attenuated double-deleted Listeria monocytogenes strains of bacteria engineered to stimulate an innate immune response and to express tumor-associated antigens that stimulate tumor-specific T cell-mediated immunity. Its GVAX is a family of vaccines made up of human cancer cell lines genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune-stimulatory cytokine. The GVAX portfolio includes vaccines for pancreatic, prostate, colon and breast cancers in addition to multiple myeloma.

Overall, Aduro has three specific tech platforms, all designed to exploit the body’s natural immune system. They are LADD, TING and the B-select monoclonal antibody platform.

On June 7, Aduro initiated a Phase Ib clinical trial of ADU-214 in combination with Opdivo (nivolumab) to treat advanced lung cancer. ADU-214 is based on the LADD tech platform. Janssen was conducting the global trial.

The trial was designed to evaluate the safety and efficacy of ADU-214 in combination with Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, Opdivo (nivolumab). The trial was focused on patients with mesothelin-positive, relapsed/refractory Stage IIIB or Stage IV adenocarcinoma of the lung.

At the time, Stephen T. Isaacs, chairman, president and chief executive officer of Aduro stated, “Based on single agent data from a Phase I dose-escalation study in patients with advanced-stage relapsed or refractory non-small cell lung presented at the 2017 International Association for the Study of Lung Cancer’s World Conference, Janssen made the decision to advance ADU-214 in combination with an anti-PD-1 checkpoint inhibitor. The initial data demonstrated that five out of nine patients treated with single-agent ADU-214 achieved a best response of stable disease, with one patient having received 25 cycles of treatment at the time of data cut off.”

According to Aduro’s 8-K filing with the United States Securities and Exchange Commission (SEC), the termination will be effective on December 24, 2018.

Although the Janssen partnership appears to be over, Aduro still has existing deals with Novartis, Merck, Johns Hopkins University and the University of California, Berkeley (CAL)for its products targeting the STING pathway. STING is a central mediator of innate immunity. When stimulated, it causes the expression of type I interferon, cytokines and T cell recruitment factors, which then active macrophages and dendritic cells, natural killer (NK) cells, and prime tumor-specific T cells.

https://www.biospace.com/article/3-months-after-launching-a-phase-ib-trial-janssen-terminates-collaboration-deal-with-aduro-biotech/

Intersect ENT strength attributed to Sinuva appearance on Anthem drug list

Intersect ENT’s (XENT) Sinuva nasal implant appears on Anthem’s (ANTM) national drug list, which is being pointed to as the reason for the stock’s early strength, according to contacts. Intersect ENT shares are up about 5% to $30.08 in early trading.
https://thefly.com/landingPageNews.php?id=2798559

Bausch unit announces publication of Phase 3 data on Bryhali Lotion

Ortho Dermatologics and its parent company, Bausch Health Companies, announced that the Journal of Drugs in Dermatology has published results of two Phase 3 randomized controlled trials examining the safety and efficacy of BRYHALITM Lotion, 0.01%, an investigational potent to superpotent** corticosteroid, in the treatment of moderate-to-severe plaque psoriasis. BRYHALI Lotion has a Prescription Drug User Fee Act action date of October 5, 2018. In the studies, BRYHALI Lotion was consistently more effective than vehicle in achieving treatment success, which was defined as at least a two-grade improvement from baseline in an Investigator Global Assessment score, and ‘clear’ or ‘almost clear’ skin. By week eight, 36.5% and 38.4% of BRYHALI Lotion patients had achieved treatment success, compared to 8.1% and 12% of patients receiving vehicle. At four weeks post treatment, no rebound of symptoms was observed in patients using BRYHALI Lotion. BRYHALI Lotion was also found to be well-tolerated, with a similar number of patients in the BRYHALI Lotion and vehicle groups reporting adverse events (21.5% and 23.9%, respectively). The most common adverse reactions were upper respiratory tract infection, application site dermatitis and hyperglycemia. The U.S. Food and Drug Administration has accepted the New Drug Application for BRYHALI Lotion with a Prescription Drug User Fee Act action date of October 5, 2018.

https://thefly.com/landingPageNews.php?id=2798249

Pacira price target raised to $49 from $45 at Canaccord

Canaccord analyst Dewey Steadman maintained a Hold rating on Pacira Pharmaceuticals (PCRX) and raised his price target to $49 from $45. Recently reported IQVIA monthly data for August show a major acceleration of volume and revenue growth vs. a year ago as well as substantial alignment in growth trends with Symphony Health data, Steadman tells investors in a research note. Longer term, however, he remains concerned about the potential advent of competition from Heron’s (HRTX) HTX-011 with what some consider to be a superior clinical data set to Exparel, and expects Pacira shares could be rangebound for the near future following strong recent performance.

https://thefly.com/landingPageNews.php?id=2798301