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Heat Biologics Provides Update on Its HS-410 Phase 2 Monotherapy Bladder Cancer Trial Arm

On February 25, 2016 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported that the company will no longer enroll new patients in its Phase 2 monotherapy trial arm evaluating HS-410 alone for the treatment of non-muscle invasive bladder cancer (NMIBC) (Press release, Heat Biologics, FEB 25, 2016, View Source [SID:1234509177]).

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Heat added the monotherapy trial arm in response to the intermittent global shortage of standard of care Bacillus Calmette-Guérin (BCG) in early 2015. The shortage has since then been resolved and as such, Heat will no longer enroll new patients in this trial arm based on discussions with the U.S. Food and Drug Administration (FDA). The decision does not relate to concerns regarding the safety profile of HS-410. The 16 patients currently enrolled, out of the anticipated 25 patients, can continue receiving HS-410 monotherapy per the study protocol. Heat anticipates reporting topline 6-month data from these 16 patients in the fourth quarter of 2016, contemporaneous with reporting data from the company’s BCG combination cohorts.

This decision does not impact the three additional randomized Phase 2 trial arms evaluating HS-410 in combination with BCG for the treatment of NMIBC. As previously announced, Heat completed enrollment of the 75 patients for these three combination trial arms in October 2015 and continues to expect to report one-year topline efficacy, immune-response and safety data in the fourth quarter of 2016.

About HS-410 (vesigenurtacel-L)

HS-410 is an investigational product candidate for NMIBC based on Heat’s proprietary ImPACT immunotherapy platform, designed to generate CD8+ "killer" T cells that attack cancer cells. HS-410 is currently being evaluated in a Phase 2, placebo-controlled NMIBC trial at multiple centers and has been granted U.S. FDA Fast Track Designation for the treatment of NMIBC.

Skin penetration and sun protection factor of five UV filters: effect of the vehicle.

To gain information about efficacy and safety of sunscreens, we compared the skin penetration of ultraviolet (UV) filters from two vehicles, i.e. an oil-in-water (O/W) emulsion gel and petrolatum jelly both in vitro and in vivo, as well as the corresponding pharmacological effect, i.e. the sun protection factor (SPF) in vivo. The UV filters studied were benzophenone-3 (BPH), ethylhexyl methoxycinnamate (EHM), butyl methoxydibenzoyl methane, ethylhexyl salicylate and homosalate. The human skin penetration of these five chemicals from the two vehicles was determined both in vitro using Franz cells and in vivo using a standardized tape-stripping method. The SPF of the two sunscreens was determined in vivo following the COLIPA guidelines. In vitro none of the filters permeated through the skin after 6 h of product application and very little could be found in the skin. BPH and EHM were the only UV filters found in the dermis (both after 30 min and 6 h). An effect of the vehicle could be noticed only for BPH after 30 min in the dermis and 6 h in both dermis and epidermis. In vivo, no differences in the amount of individual UV filters (in % of the applied dose) in the 15 first strips of the stratum corneum (SC) were found following 30 min of application of the formulations; however, the amount of UV filters that were retained in the SC was significantly higher (around 3 times) with the O/W emulsion gel than with the petrolatum jelly. This difference between the two vehicles was also of consequence for the SPF in vivo measured 30 min after application of the products (SPF congruent with 18 with the O/W emulsion gel compared to SPF congruent with 10 with the petrolatum jelly). By choosing the right vehicle or optimizing it, not only sunscreen products can be significantly improved in terms of pharmacological efficacy but the potential toxicological risk associated with the skin penetration of UV filters may be significantly reduced.
Copyright 2003 S. Karger AG, Basel

Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08).

Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin.
An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar’s matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%.
Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events.
Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Cancer stem cells: Genoscience Pharma welcomes Pharmacyclics founders to its board of directors

On February 24, 2016 Genoscience Pharma, a biopharmaceutical company dedicated to discovering and developing cancer treatment drugs, reported the arrival of four new members to its board of directors (Press release, GenoScience, FEB 24, 2016, View Source [SID:1234509200]). Dr Mahkam Zanganeh, Robert Duggan and Manmeet Soni, respectively the former chief operating officer, chief executive officer and chief financial officer of Pharmacyclics, are joining the board along with Chaim Hurvitz, who has worked in many management roles for Teva International Group. The new members will support the strategic and financial development of Genoscience, alongside existing board members – Antoine Béret, Jean-Marc Feryn, Vincent Fert and Chalom Sayada. Their arrival is accompanied by an increase in capital, the terms of which have not been disclosed.

The four new members are all recognized biotechnology entrepreneurs. While at Pharmacyclics Pharmaceuticals, in less than seven years, Mahkam Zanganeh and Robert Duggan developed and brought to the market Imbruvica, a first-in-class compound treating patients with Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL) and Waldenstrom’s macroglobulinemia (WM). In May 2015, Abbvie acquired Pharmacyclics for $21Bn (€18.9Bn), one of the biggest buyouts for a biotechnology company to date.

Genoscience Pharma’s most advanced compound, GNS561, is in preclinical development for the treatment of liver cancer. It is a small active molecule that works against a new target. It is unique as it targets not only hepatic cancerous cells, but also the progenitors of the cancerous hepatocyte stem cells. GNS561 begins its regulatory process with the aim of starting the first-in-man phase 1b/2a trials in 2017. Preclinical studies have demonstrated GN561’s potential to become a major therapeutic breakthrough in the treatment of hepatocellular carcinoma.

"I am delighted to welcome this high caliber team to our board of directors. Robert Duggan and Mahkam Zanganeh’s experience in the development of anti-tumor molecules will be a credit to our company," said Prof. Philippe Halfon, president and founder of Genoscience Pharma. "It is an honor and a true mark of recognition to be joined by such a team, who participate very selectively in high potential projects. Their scientific expertise in pharmaceutical development will undoubtedly help us achieve our objectives and get to phase 2 quickly."

"The next challenge in oncology is to cure cancer patients by targeting the seed of the disease; cancer stem cells which cause cancer to recur," said Dr. Mahkam Zanganeh. "The strategy proposed by Genoscience Pharma is unique and will allow us to make a decisive step forward in curing cancer."

About cancer stem cells

Since 2012, Genoscience has been involved in an ambitious program to discover and develop compounds that target cancer stem cells. These stem cells, which are ultra-resistant to traditional chemotherapy and radiotherapy, form a minority subpopulation of the cells in a tumor and are responsible for tumor growth and metastases. They renew themselves indefinitely, differentiating themselves to form and maintain the tumor tissue. These cells do not respond to conventional chemotherapy that targets the majority of differentiated tumor cells. This explains the indefinite development of tumors as well as metastases and relapses. Consequently, eradicating cancer stem cells is essential in order to achieve lasting clinical remission and to improve the prognosis of cancer patients.

Genoscience is one of the pioneers in this emerging domain of cancer biology, which aims to revolutionize the traditional approach to treating cancer. Genoscience’s main candidate, GNS561, is also under evaluation for treating other cancers (kidney and colorectal), which could respond to its first-in-class action mechanism.

About liver cancer

Liver cancer (or HCC – hepatocellular carcinoma) is the third most common cause of death by cancer in the world[1]. The medical needs for treating it are considerable and not yet resolved. The only existing chemotherapy treatment for HCC is sorafenib, which slightly increases survival rates, but has many adverse effects[2].

New Publication Demonstrates the Utility of Nanomerics’ Molecular Envelope Technology (MET) in the Treatment of Experimental Brain Tumours

On February 24, 2016 Nanomerics’ scientists reported they have demonstrated that encapsulating chemotherapy drugs within Nanomerics’ MET nanoparticles diverts the drug from the bone marrow, while enabling higher levels of drug to access the brain (Press release, Nanomerics, FEB 24, 2016, View Source [SID:1234509184]). Animals intravenously dosed with Nanomerics’ MET – lomustine formulations showed significantly improved survival rates when compared to the drug in solution and the effect of the drug on the bone marrow was comparable to the drug in solution. The work is described in a new paper published in Pharmaceutical Research View Source This data demonstrates the further utility of Nanomerics’ MET via the intravenous route. The MET formulation worked by enabling a higher dose of the hydrophobic drug lomustine to be administered and this higher dose did not result in higher levels of drug in the bone and liver, whereas levels of the drug in the brain were increased. The bone marrow is a major site of toxicity for alkylating agents such as lomustine and dose limiting myelosuppression compromises brain tumour therapy significantly.

Nanomerics’ Chief Scientific Officer states, "this study provides evidence that Nanomerics’ MET nanoparticles are able to avoid the bone marrow and indeed the liver on intravenous administration and provide a method of administering a hydrophobic alkylating agent for the treatment of brain tumours."