Year: 2016

8-K – Current report

On February 2, 2016 Array BioPharma Inc. (NASDAQ: ARRY) reported results for the second quarter ending December 31, 2015 of its fiscal year and provided an update on the progress of its key clinical development programs (Filing, 8-K, Array BioPharma, FEB 2, 2016, View Source [SID:1234508933]).

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Ron Squarer, Chief Executive Officer of Array, noted, "We were excited this quarter to share positive results from the first global Phase 3 trial of binimetinib in patients in NRAS-mutant melanoma. We plan to submit these results to regulators during 2016. In addition, we continue to make important progress with binimetinib and encorafenib in several other clinical trials, and expect to announce top-line results from COLUMBUS in BRAF-mutant melanoma in 2016."

KEY PIPELINE UPDATES
Binimetinib (MEK162) and encorafenib (LGX818)

NEMO meets primary endpoint; regulatory filing expected in 1H 2016
COLUMBUS top-line results expected in 1H 2016; regulatory filing expected in 2H 2016
New Phase 3 global registration trial in BRAF-mutant colorectal cancer expected to start in 2016

Update on Phase 3 trials
In December 2015, Array reported top-line results from the ongoing Phase 3 NEMO clinical trial of binimetinib in patients with advanced NRAS-mutant melanoma. The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment, with a hazard ratio of 0.62, [95% CI 0.47-0.80] and a p-value of less than 0.001. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm. In the trial, binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS melanoma patients.

Array plans to submit binimetinib to regulatory authorities for marketing approval in NRAS-mutant melanoma during the first half of 2016. Results from the NEMO trial including progression free survival, overall survival, objective response rate, safety and prespecified subgroup analyses including outcomes in patients who received prior treatment with immunotherapy will be presented at a medical conference in 2016.

In addition, Array expects top-line results from Part 1 of the COLUMBUS trial in the first half of 2016 and projects a regulatory filing of binimetinib and encorafenib in 2016. In October 2015, Part 2 of COLUMBUS achieved its target patient enrollment. The MILO Phase 3 study in patients with low-grade serous ovarian cancer continues to enroll patients, and Array estimates enrollment to be complete in 2016 with the availability of top-line data, along with a projected regulatory filing, in 2017.

Based on the strength of the Phase 2 combination data with encorafenib in patients with BRAF-mutant colorectal cancer shared at the 2015 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s (ESMO) (Free ESMO Whitepaper) World Congress of Gastrointestinal Cancer, Array plans to initiate a Phase 3 global registration trial in that patient population in 2016.

Collaboration with Pierre Fabre
In November 2015, Array and Pierre Fabre announced a collaboration agreement for binimetinib and encorafenib. Under the terms of the agreement, Array received an upfront payment of $30 million in January 2016 and retains exclusive commercialization rights for binimetinib and encorafenib in key territories, including the United States and Japan. Pierre Fabre will have exclusive rights to commercialize both products in other territories, including Europe, Asia and Latin America. Array is entitled to receive up to $425 million if certain development and commercialization milestones are achieved, and is eligible for robust, tiered double-digit royalties. Array and Pierre Fabre have agreed to split future development costs on a 60:40 basis (Array:Pierre Fabre) with initial funding committed for new clinical trials in colorectal cancer and melanoma. The agreement was reviewed and approved by the European Commission on Competition in December 2015. All currently active binimetinib and encorafenib clinical trials remain substantially funded through completion by Novartis.

Pierre Fabre Oncology, a business unit of the global 10,000-employee Pierre Fabre company, is supported by over 1,000 employees with a strong focus on European markets. In 2014, worldwide annual sales of Pierre Fabre Oncology products surpassed $200 million on the strength of the Oral Navelbine, Javlor and Busilvex brands. In addition, Pierre Fabre has a significant commitment and track record in pharmaceutical R&D, developing products for patients afflicted with lung, breast and other solid tumors and hematological cancers.

ARRY-797 (ARRY-371797) – Phase 2 trial on-going in patients with LMNA A/C-related dilated cardiomyopathy (DCM)
Array is conducting a 12-patient Phase 2 study to evaluate the effectiveness and safety of ARRY-797 in patients with LMNA A/C-related DCM, a serious, genetic cardiovascular disease. By age 45, approximately 70% of patients with LMNA A/C-related DCM will have died, suffered a major cardiac event, or will have undergone a heart transplant. Data on the primary endpoint of mean change in 6-minute walk test (6MWT) at 12 weeks relative to baseline exceeds benchmarks set by a number of drugs for rare diseases recently approved on the basis of the 6MWT as a primary endpoint. Secondary endpoints, including changes in N-Terminal pro-Brain-derived Natriuretic Peptide (NT-proBNP, a serum biomarker of heart failure severity), and patient reported outcomes, are directionally consistent with the primary endpoint. Enrollment in this trial is complete. Data for patients followed through 48 weeks supports the durability of effect. Taken together, the data to date suggest a path forward for this program. Results with additional patient follow-up will be presented at an appropriate medical conference in 2016.

Selumetinib (partnered with AstraZeneca) – Three registration trials advancing in NSCLC (SELECT-1), thyroid cancer (ASTRA) and neurofibromatosis type 1
AstraZeneca continues to advance selumetinib in three registration trials: SELECT-1 in patients with KRAS-mutant non-small cell lung cancer, a registration trial in patients with neurofibromatosis type 1 and ASTRA in patients with differentiated thyroid cancer. AstraZeneca expects to share top-line results from SELECT-1 in mid-2016.

FINANCIAL HIGHLIGHTS
Cash, cash equivalents, marketable securities and accounts receivable totaled $185.4 million at the end of the quarter. Accounts receivable primarily consist of receivables expected to be paid by Novartis within three months and the $30.0 million license fee from Pierre Fabre, which was received in January 2016. In March 2015, binimetinib and encorafenib became wholly-owned assets, which prompted changes to the classification of revenue and expenses for the programs. The new expense classifications were included in the fourth quarter of fiscal 2015 financial results and, beginning in the first quarter of fiscal 2016, Array reports revenue from Novartis reimbursements under its agreements with Novartis for binimetinib and encorfenib as a separate line item called "reimbursement revenue."

Second Quarter of Fiscal 2016 Compared to First Quarter of Fiscal 2016 (Sequential Quarters Comparison)
Revenue for the second quarter of fiscal 2016 was $35.4 million, compared to $16.2 million for the prior sequential quarter. The $19.2 million increase in revenue was primarily due to higher reimbursement revenue from Novartis. Cost of partnered programs for the second quarter of fiscal 2016 was $5.7 million, compared to $6.2 million for the prior quarter. Research and development expense was $41.4 million, compared to $21.0 million in the prior quarter. The increase in research and development expense is primarily related to the ongoing transition of binimetinib and encorafenib trials from Novartis to Array. Net loss for the second quarter was $24.2 million, or ($0.17) per share, and was $21.0 million, or ($0.15) per share in the prior quarter.

Second Quarter of Fiscal 2016 Compared to Second Quarter of Fiscal 2015 (Prior Year Comparison)
Compared to the same quarter of fiscal 2015, revenue for the second quarter of fiscal 2016 increased $8.5 million primarily due to $27.3 million in reimbursement revenue from Novartis. Cost of partnered programs decreased $7.4 million compared to the second quarter of fiscal 2015 primarily due to binimetinib development costs being presented as research and development expense instead of cost of partnered programs upon becoming wholly-owned programs. Research and development expense increased $29.5 million compared to the second quarter of fiscal 2015 due to the categorization of binimetinib costs, as well as new spending on encorafenib. Net loss for the second quarter of fiscal 2016 was $24.2 million, or ($0.17) per share, and was $8.6 million, or ($0.06) per share, for the same quarter in fiscal 2015.

Six Months of Fiscal 2016 Compared to Six Months of Fiscal 2015 (Prior Year Comparison)
For the six months ended December 31, 2015, revenue was $51.6 million, compared to $33.0 million for the same period in fiscal 2015. Net loss for the six months ended December 31, 2015, was $45.2 million, or ($0.32) per share, compared to a net loss of $36.2 million, or ($0.27) per share, in the comparable prior year period.

MISSION THERAPEUTICS RAISES £60 MILLION TO PROGRESS DEVELOPMENT OF NOVEL DUB INHIBITORS FROM INNOVATIVE DRUG PLATFORM

On February 2, 2016 MISSION Therapeutics, a drug discovery and development company focused on selectively targeting deubiquitylating enzymes to treat cancer, neurodegenerative and other diseases, reported that it has raised £60 million (Press release, Cancer Research Technology, FEB 2, 2016, View Source [SID1234523506]). The financing was jointly led by Imperial Innovations Businesses LLP ("Innovations") and new investor Woodford Patient Capital Trust Plc ("WPCT"), with follow-on investment from existing shareholders Sofinnova Partners, SR One, Roche Venture Fund and Pfizer Venture Investments.

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The £60 million will enable MISSION to maximize the potential of its world leading DUB platform and advance a series of first-in-class small molecule drugs candidates targeting specific DUBs into clinical development.

Anker Lundemose, Chief Executive Officer, MISSION Therapeutics commented: "MISSION Therapeutics has attracted one of the highest profile investor syndicates in Europe. We welcome WPCT and thank our existing investors for their continued support. This is strong endorsement of our unique discovery platform and will enable us to maximize the potential of multiple lead compounds for diverse therapeutic indications. 2016 will see us progress our advanced programs into regulatory preclinical development and deepen our pipeline, from a position of increased financial strength."

Rob Woodman, Director of Healthcare Ventures, Imperial Innovations added: "We believe MISSION’s world-class DUB platform has the potential to deliver innovative treatments in indications of high unmet need including neurodegenerative diseases and cancer. The investor group are pleased to support the creative management team in realising the full potential of the ground-breaking discovery chemistry as MISSION enters its next, clinically-centred stage of growth."

DUBs are involved in multiple cellular processes, including DNA damage and cell proliferation, and the inhibition of these enzymes has considerable potential for the generation of novel drugs for treating cancer and other unmet medical needs, including neurodegenerative disease, muscle wasting and infectious disease. Despite significant efforts within the pharmaceutical sector, there is a lack of DUB inhibitors in clinical development.

Adaptimmune and GSK expand Strategic Immunotherapy Collaboration

On February 2, 2016 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in the use of T- cell receptor (TCR) engineered T-cell therapy to treat cancer, and GlaxoSmithKline plc (LSE/NYSE: GSK) reported that the companies have expanded the terms of their strategic collaboration agreement to accelerate Adaptimmune’s lead clinical cancer program, an affinity enhanced T-cell immunotherapy (GSK3377794) targeting NY-ESO-1, toward pivotal trials in synovial sarcoma(Press release, Adaptimmune, FEB 2, 2016, View Source [SID:1234508937]).

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Adaptimmune and GSK announced a strategic collaboration and licensing agreement in June 2014 for up to five programs, including the lead NY-ESO TCR program. GSK has an option on the NY-ESO-1 program through clinical proof of concept and, on exercise, will assume full responsibility for the program.

"We are delighted to broaden our collaboration with GSK, which is also fully committed to the development of this revolutionary T-cell therapy," commented James Noble, Adaptimmune’s Chief Executive Officer. "We believe that our affinity enhanced T-cell programs have the potential to deliver important clinical benefit to cancer patients, and it is therefore essential that we accelerate our efforts to meet their needs. We are working closely with GSK to expedite development of our affinity enhanced T-cell therapy targeting NY-ESO, and if we succeed in generating pivotal data consistent with that of our ongoing studies, we believe it has the potential to be the first engineered T-cell therapy to reach the market."

Dr. Axel Hoos, SVP Oncology R&D GSK said, "At GSK we’re progressing a pipeline of immuno-oncology therapies to stimulate anti-tumor immunity in patients. As we highlighted to investors at our R&D event last year, this Adaptimmune collaboration is a key element of that pipeline and is part of a comprehensive program for cell and gene therapy. With this expanded collaboration, we have the opportunity to accelerate the lead program in synovial sarcoma toward pivotal trials and also to investigate several other tumor types and combine the T-cell therapy with immune-modulating therapies such as checkpoint inhibitors."

Under the terms of the expanded agreement, the companies will accelerate the development of Adaptimmune’s NY-ESO therapy into pivotal studies in synovial sarcoma and will explore development in myxoid round cell liposarcoma. Additionally, the companies may initiate up to eight proof-of-principle studies exploring combinations with other therapies, including checkpoint inhibitors. According to the expanded development plan, the studies will be conducted by Adaptimmune with GSK effectively funding the pivotal studies and sharing the costs of the combination studies via a success based milestone structure.

Previous guidance relating to the collaboration disclosed potential cash payments to Adaptimmune of approximately $350m over the first 7 years from 2014 in relation to NY-ESO and two further programs. Given the changes announced today, and the advances made across the collaboration, Adaptimmune is updating and expanding this disclosure. Under the terms of the expanded agreement, the potential development milestones Adaptimmune is eligible to receive solely in relation to the NY-ESO program could amount to approximately $500 million, excluding previously received payments, if GSK exercises its option and successfully develops NY-ESO in more than one indication and more than one Human Leukocyte Antigen (HLA) type. In addition, Adaptimmune would receive tiered sales milestones and, as previously disclosed, mid-single to low double digit royalties on worldwide net sales. GSK has the right to nominate up to four additional targets in due course and Adaptimmune is eligible to receive further significant undisclosed milestone payments in relation to these earlier stage target programs.

Adaptimmune has also reiterated its prior cash burn guidance, which remains unchanged as the majority of the expansion and acceleration costs will be funded by GSK. For the full year 2016, the company expects its cash burn to be between $80 and $100 million, excluding cash burn associated with business development activities, and expects its cash position at December 31, 2016, including cash, cash equivalents, and short term deposits, to be at least $150 million.

About affinity enhanced T-cell candidates

Adaptimmune’s affinity enhanced T-cell candidates are novel cancer immunotherapies that have been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. Using its proprietary technology, Adaptimmune has created a pipeline of affinity enhanced T-cell therapies targeting certain antigens, including cancer testis antigens such as NY-ESO. NY-ESO-1 is one of the bestcharacterized and most immunogenic cancer testis antigens, and is frequently expressed by tumors of different origins and in advanced tumors. The company’s trials in the NY-ESO-1 program in multiple myeloma, melanoma, sarcoma and ovarian cancer continue to generate encouraging results.

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.

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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.