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PharmaMar and Specialised Therapeutics Asia sign licensing and marketing agreement for APLIDIN® (plitidepsin) covering several Asian countries

On February 2, 2016 PharmaMar (MSE:PHM) reported an agreement with Singapore-based Specialised Therapeutics Asia Pte, Ltd (STA) to market marine-based anti-tumour compound APLIDIN (plitidepsin) for the treatment of haematological tumours in 12 Asian countries: Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Papua New Guinea, Philippines, Singapore, Thailand and Vietnam (Press release, PharmaMar, FEB 2, 2016, View Source [SID:1234508936]).

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APLIDIN (plitidepsin), the second anti-tumour compound to be developed by PharmaMar from a marine organism, is currently undergoing development for the treatment of haematological tumours. A number of clinical trials are currently under way in relapsed/refractory multiple myeloma, such as the ADMYRE Phase III trial, as well as a Phase II trial in T-cell lymphoma. Plitidepsin has been granted orphan drug status by the regulatory agencies in Europe (EMA) and the US (FDA).

José María Fernández Sousa-Faro, Chairman of PharmaMar, commented, "We are proud to enter into agreements with laboratories such as STA that enable us to ensure that all patients who need plitidepsin will have access to it. We are firmly committed to advancing in the development of innovative oncology therapies."

Carlo Montagner, CEO of Specialised Therapeutics Asia: "We look forward to working with PharmaMar to ensure this valuable multiple myeloma therapy is available as soon as possible to patients in key South East Asia regions, as well as in Australia and New Zealand". He added "Aplidin may be highly valuable as a new therapeutic for this difficult to treat cancer. While multiple myeloma remains relatively rare, it is an insidious disease with one of the lowest survival rates in oncology".

Under the terms of the agreement, PharmaMar is entitled an upfront payment, recurring payments for sales, and additional remuneration for sales and regulatory milestones attained by APLIDIN (plitidepsin). PharmaMar will retain exclusive 2 production rights and will supply the product to STA for sale in those 12 Asian countries.

Targeted DEP™ shows sustained superior performance

On February 2, 2016 Starpharma (ASX: SPL, OTCQX: SPHRY) reported the final results of the preclinical study of its HER2-targeted DEP conjugate, which achieved complete tumour regression at the last study time point of 120 days post dosing (Press release, Starpharma, FEB 2, 2016, View Source [SID:1234508928]). These results are an extension of the previously announced findings that showed complete tumour regression at 60 days post dosing with the HER2-targeted DEP conjugate.

Starpharma’s HER2-targeted DEP conjugate also significantly outperformed all other treatment groups, including Kadcyla (Trastuzumab-DM1), a Herceptin antibody-drug conjugate (ADC) currently marketed by Roche, with respect to both tumour regression and survival.

In the study, 100% of mice treated with Starpharma’s HER2-targeted DEP conjugate were tumour-free within three weeks of the commencement of treatment and remained that way for the total duration of the study. In contrast, only tumour stasis was observed during treatment in the Kadcyla group, with a maximum tumour volume inhibition of 32%1 with significant tumour regrowth occurring soon after the completion of dosing.

Starpharma Chief Executive, Dr Jackie Fairley, commented, "We are very excited by these latest results for our Targeted DEP conjugates and the feedback from commercial parties on the study data has been very positive indeed. Both the extent and the sustained nature of the anticancer effect seen with Starpharma’s DEP candidate have been considered most impressive. Discussions are now underway with a number of leading pharmaceutical companies in relation Targeted DEP conjugates and the application of Starpharma’s Targeted DEP platform to their proprietary drugs."

This study was conducted for Starpharma by an internationally recognised cancer organisation, as part of a wider program of studies to assess various Targeted DEP conjugates. The study was conducted using a well-established ovarian cancer model for assessing efficacy of therapies against HER2-positive cancer cell lines.

The results from this study clearly demonstrate significant and long term survival benefits for the Targeted DEP conjugate compared to other treatment groups, including Kadcyla.

The top 3 antibody based treatments in cancer (Rituxan, Avastin and Herceptin) had total sales in excess of $US20 billion in 2014. Targeted therapies for cancer, such as the ADCs Kadcyla and Adcetris, had combined sales in excess of US$1 billion in 2014, with Kadcyla sales growing at 144% versus the previous year. The market for ADCs is expected to grow to US$9 billion annually by 2023. 2

About the Study
These latest results are an extension of the previously announced 16th November 2015 xenograft study results at 60 days post dosing with the HER2-targeted DEP conjugate.

Groups of animals were dosed once per week for 3 weeks with the HER2-targeted DEP conujgate, Kadcyla, or a saline control. Another group of animals was treated with Herceptin twice a week for 3 weeks.

The animals treated with the HER2-targeted DEP conjugate showed vastly superior anticancer effectiveness compared with the saline, Kadcyla and Herceptin treated control groups, demonstrating significant ablation of the tumours even after the first dose. Subsequent dosing resulted in 100% of mice being completely tumour-free within three weeks after the commencement of treatment and remained such for the total duration of the study. All mice in the HER2-targeted DEP conjugate group remained within the acceptable body weight range during dosing and gained weight post dosing.

In contrast, only tumour stasis was observed during treatment in the Kadcyla group, with a maximum tumour volume reduction, as measured at study day 12, of 32% compared with the saline control group, with significant tumour regrowth occurring soon after the completion of dosing. In accordance with ethical requirements the Kadcyla and other control groups were discontinued at 42 days post dosing due to body weight loss and extensive tumour growth.

Targeted DEP Conjugates
Starpharma’s proprietary targeted DEP conjugate in this experiment consists of a dendrimer scaffold, a targeting group (in this case the monoclonal antibody, trastuzumab (Herceptin)) and a "payload" of anticancer drug.

Targeted DEP conjugates have a number of important advantages over standard ADCs including higher drug loading and manufacturing advantages.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

(Filing, 10-K, HedgePath Pharmaceuticals, FEB 1, 2016, View Source [SID:1234508943])

EISAI ACQUIRES EXCLUSIVE LICENSE FROM HUYA BIOSCIENCE INTERNATIONAL TO DEVELOP AND MARKET HDAC INHIBITOR HBI-8000 IN JAPAN AND OTHER ASIAN COUNTRIES

On February 1, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that Eisai has entered into an exclusive license agreement with HUYA Bioscience International, LLC (Headquarters: San Diego, California, United States, President, CEO, Executive Chairman & Founder: Dr. Mireille Gillings, "HUYA") to develop and market the oral histone deacetylase (HDAC) inhibitor HBI-8000 in Japan, South Korea, Thailand, Malaysia, Indonesia, Philippines, Vietnam and Singapore (Press release, Eisai, FEB 1, 2016, View Source [SID:1234508935]).

HBI-8000 is an oral HDAC inhibitor approved in China for use in the treatment of peripheral T-cell lymphoma (PTCL). Non-clinical data suggest HBI-8000 has epigenetic properties that work to regulate tumor cell growth, and the agent is believed to have immunomodulatory properties as well. HBI-8000 is at the clinical stage of testing in Japan as a treatment for PTCL, a type of non-Hodgkin’s lymphoma, under orphan drug designation from the regulatory authority in Japan. Meanwhile, a Phase I clinical study of the agent in solid tumors has been completed in the United States.

Under the agreement, Eisai has exclusive rights to develop and market HBI-8000 in the licensed territories. However, for PTCL and adult T-cell leukemia-lymphoma, HUYA will complete development of the agent for these indications and Eisai will be responsible for commercialization. According to the agreement, Eisai will pay HUYA upfront, development and commercial milestone payments as well as royalties over the term of the license, respectively.

Eisai positions oncology as a key franchise area, and is committed to providing new treatment options for patients with cancer in order to further contribute to addressing unmet medical needs that exist in the treatment of cancer as well as increase the benefits provided to patients and their families.

2About HBI-8000
HBI-8000 is a member of the benzamide class of histone deacetylase (HDAC) inhibitors designed to block the catalytic pocket of Class I HDACs. HBI-8000 is an orally bioavailable, low-nanomolar inhibitor of cancer-associated HDAC enzymes with favorable pharmacology and safety profiles. HBI-8000 inhibits cancer-associated Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10 at nanomolar concentrations and stimulates accumulation of acetylated histones H3 and H4 in tumor cells. Studies with human-derived tumor cell lines suggest that HBI-8000 inhibits the growth of many tumor cell lines via multiple mechanisms of action, including epigenetic regulation of tumor cell growth and apoptosis as well as immunomodulatory effects regulating antitumor activity.
To date, HBI-8000 has been dosed in various types of hematological and solid tumors in several clinical trials, including a Phase I trial completed in the United States. HBI-8000 is approved for the treatment of peripheral T-cell lymphoma (PTCL) in China. A Phase I clinical study of the agent in non-Hodgkin’s lymphoma is underway in Japan under orphan drug designation as a treatment for PTCL by the regulatory authority in Japan.

About HDAC
Removing acetyl groups from lysine amino acids on histones to encourage stronger binding of chromatin structures to suppress gene transcription, and adding acetyl groups to weaken binding of chromatin structures to promote transcriptional activity play an important role in regulation of gene transcription on histones. HDAC are enzymes that remove acetyl groups from lysine amino acids on histones, and it is thought that by inhibiting HDAC to allow acetyl groups to accumulate on histones and relax chromatin structures promotes gene transcription activity. In tumor cells, inhibiting HDAC suppresses tumor growth by facilitating the transcriptional activity of cancer suppressing genes and inducing both apoptosis in tumor cells as well as cell cycle arrest.

Aduro Biotech Receives $22.4 Million in Clinical Development Milestone Payments From Janssen

On February 01, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the company received $22.4 million in clinical development milestone payments from Janssen Biotech, Inc., the company’s license partner for ADU-214, ADU-741 and other products using Aduro’s LADD technology platform for the treatment of specific cancers(Press release, Aduro BioTech, FEB 1, 2016, View Source;p=RssLanding&cat=news&id=2133977 [SID:1234508932]). Janssen is responsible for all clinical development for the product candidates within the license agreements.

"Our relationship with Janssen has been exceptionally productive, with ADU-214 for the treatment of lung cancer and ADU-741 for the treatment of prostate cancer advancing in clinical studies," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "We believe these therapeutics may offer important alternatives for patients suffering from these aggressive cancers."

In May 2014 and October 2014, Aduro entered into two separate agreements with Janssen, granting exclusive, worldwide licenses to ADU-741 and other product candidates engineered for the treatment of prostate cancer, and ADU-214 and other product candidates engineered for the treatment of lung cancer and certain other cancers, based on its novel LADD immunotherapy platform.