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Foundation Medicine Adds New Immunotherapy Features to Its Market-Leading Products

On August 22, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported the addition of new clinical markers to its FoundationOne and FoundationOne Heme products, which are designed to enhance oncologists’ insight into potential response to immunotherapies (Press release, Foundation Medicine, AUG 22, 2016, View Source [SID:1234514660]). This ability to determine TMB and MSI from its assays is additional to the existing comprehensive profiling of genes provided by FoundationOne and FoundationOne Heme. Taken together, the molecular information provided by Foundation Medicine provides unique insights to physicians and enhances their ability to predict response to immunotherapies, identify targeted therapeutic options, and improve access to clinical trials all from a single assay.

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"Cancer immunotherapies are at the forefront of cancer treatment, and new, quantitative approaches are needed to predict clinical responses to this important, but also expensive, class of therapies," said Vincent Miller, M.D., chief medical officer of Foundation Medicine. "Prior to our ability to measure TMB and MSI with FoundationOne, these biomarkers could only be detected separately, either through tests such as immunohistochemistry, polymerase chain reaction (PCR) or whole exome sequencing. Importantly, high-quality, predictive TMB scoring can only be accurately performed with sophisticated algorithms developed to work with broad, hybrid capture-based platforms that can analyze all relevant alterations simultaneously. Integrating this capability to measure TMB and MSI with one tissue sample, and reported in one test, represents an important advance in clinical care."

A growing body of evidence, most recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting this year, validates the ability of a new independent marker, TMB, to predict the likelihood of response to cancer immunotherapies. TMB is reported as the total number of DNA mutations per megabase in a tumor sequence. This phenomenon has been validated across a wide range of tumor types, including advanced bladder cancer, lung cancer, breast cancer, colorectal cancer, advanced head and neck cancer and melanoma. Some tumors develop high TMB as a result of defective mismatch repair of DNA, a condition in which the length of certain DNA areas becomes more widely varied than normal. This condition, which is referred to as MSI-high and MSI-high tumors, almost always has a high TMB.

"The ability to accurately measure multiple biomarkers simultaneously, including TMB and MSI, is an important advance for the field of cancer immunotherapy, and one that is unique to Foundation Medicine," said Thomas George, M.D., GI oncology program director, University of Florida. "Foundation Medicine’s combination of advanced sequencing platforms and highly-specific algorithms gives me access to all relevant genomic biomarkers for my patients at once, helping to save both time and tissue."

"We were encouraged by the findings presented at ASCO (Free ASCO Whitepaper), including the possibility of identifying patients more likely to benefit from checkpoint inhibitor immunotherapy," said Dr. Miller. "Our goal is to empower doctors and patients with a full range of relevant, actionable genomic information, and we’re excited to offer our distinctive solution to estimate TMB and MSI simultaneously and with exceptional accuracy, supported by sophisticated algorithms and rooted in contextual insights from our knowledgebase FoundationCORE. This is something no other next-generation sequencing platform offers."

Independent of the FoundationOne and FoundationOne Heme assays, Foundation Medicine also offers testing for PD-1 and PD-L1 protein expression, providing, in combination with the FoundationOne assays, a full suite of cancer immunotherapy assays for oncologists.

Other events

As disclosed in its Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2016, on August 3, 2016, Momenta Pharmaceuticals, Inc. (the "Company") discontinued further accrual of its Part B, or Phase 2, portion of its Phase 1/2 clinical trial evaluating necuparanib in combination with nab-paclitaxel (ABRAXANE) and gemcitabine in patients with advanced metastatic pancreatic cancer. The decision to discontinue enrollment was based on the recommendation of the independent Data Safety Monitoring Board for the trial following the outcome of a planned interim futility analysis. On August 22, 2016, after confirming the results of the futility analysis and reviewing the unblinded safety and efficacy data and the results of various sensitivity and subgroup analyses, the Company decided to discontinue the necuparanib program.

On February 29, 2016, the Company filed with the Securities and Exchange Commission (the "Commission") a shelf registration statement on Form S-3 (File No. 333-209813) (the "Registration Statement"), which became immediately effective upon filing.

On September 1, 2016, the Company will be filing with the Commission a prospectus supplement, dated September 1, 2016, to the prospectus included in the Registration Statement in connection with the offer and sale of shares of the Company’s common stock from time to time through Stifel, Nicolaus & Company, Incorporated ("Stifel"), pursuant to an At-the-Market Equity Offering Sales Agreement, dated April 21, 2015, between the Company and Stifel, which was filed with the Commission as Exhibit 10.1 to the Company’s Current Report on Form 8-K on April 21, 2015.

In connection with the filing of the prospectus supplement, the Company is filing as Exhibit 5.1 hereto a copy of an opinion of its counsel, Latham & Watkins LLP, regarding the validity of the securities being registered under the prospectus supplement.

Puma Biotechnology Announces European Medicines Agency Validation of Marketing Authorization Application for PB272 (Neratinib) as Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer in Europe

On August 22, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that the Marketing Authorization Application (MAA) for neratinib has been validated by the European Medicines Agency (EMA) (Press release, Puma Biotechnology, AUG 22, 2016, View Source [SID:1234514664]). Validation of the MAA confirms that the submission is complete and starts the EMA’s formal review process. The potential indication for neratinib is for the extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with trastuzumab (Herceptin)-based adjuvant therapy. The MAA submission is based upon the ExteNET Phase III study, which reached its primary endpoint whereby neratinib demonstrated a statistically significant reduction of risk of invasive disease recurrence or death versus placebo.

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"Although the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need for further improvement in outcome in order to attempt to further reduce this risk of recurrence following trastuzumab therapy," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "Neratinib may be able to provide this type of improvement to further help the patients with this disease. We look forward to working with the CHMP/EMA during their review of this submission."

In the ExteNET study, treatment with neratinib resulted in a 33% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The 2-year invasive disease free survival (DFS) rate for the neratinib arm was 93.9% and the 2-year DFS rate for the placebo arm was 91.6%. For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 49% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). For the patients with hormone receptor positive disease, the 2-year DFS rate for the neratinib arm was 95.4% and the 2-year DFS rate for the placebo arm was 91.2%. Results of the study were published online in The Lancet Oncology on February 10, 2016.

The most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). Patients who received neratinib in the ExteNET trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. Interim results of a Phase II study of neratinib monotherapy in patients with HER2-positive early stage breast cancer who have previously been treated with adjuvant trastuzumab, where patients received anti-diarrheal prophylaxis with loperamide, demonstrated that treatment with prophylactic loperamide reduced the rate of grade 3 or higher diarrhea to between 13.0% and 18.5%.

About ExteNET

The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in women with early stage HER2-positive breast cancer. The trial randomized 2,840 patients in 41 countries with early stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of two years after randomization in the trial. The primary endpoint of the trial was DFS.

Pfizer To Acquire Medivation

On August 22, 2016 Pfizer Inc. (NYSE:PFE) and Medivation, Inc. (NASDAQ:MDVN) reported that they have entered into a definitive merger agreement under which Pfizer will acquire Medivation, a biopharmaceutical company focused on developing and commercializing small molecules for oncology, for $81.50 a share in cash for a total enterprise value of approximately $14 billion (Press release, Pfizer, AUG 22, 2016, View Source [SID:1234514656]). The Boards of Directors of both companies have unanimously approved the merger, which is expected to be immediately accretive to Pfizer’s Adjusted Diluted EPS upon closing, approximately $0.05 accretive in the first full year after close with additional accretion and growth anticipated thereafter. Pfizer does not expect the transaction to impact its current 2016 financial guidance.

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"The proposed acquisition of Medivation is expected to immediately accelerate revenue growth and drive overall earnings growth potential for Pfizer," said Ian Read, chairman and chief executive officer, Pfizer. "The addition of Medivation will strengthen Pfizer’s Innovative Health business and accelerate its pathway to a leadership position in oncology, one of our key focus areas, which we believe will drive greater growth and scale of that business over the long-term. This transaction is another example of how we are effectively deploying our capital to generate attractive returns and create shareholder value."

Medivation’s portfolio includes XTANDI (enzalutamide), an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. XTANDI is the leading novel hormone therapy in the United States today and generated approximately $2.2 billion in worldwide net sales over the past four quarters, as recorded by Astellas Pharma Inc., with whom Medivation entered an agreement in 2009 to develop XTANDI globally and commercialize jointly in the U.S. Since its approval for advanced metastatic prostate cancer by the U.S. Food and Drug Administration in 2012, XTANDI has treated 64,000 men to date in the U.S. alone. Medivation and Astellas have built a robust development program for XTANDI, including two Phase 3 studies in non-metastatic prostate cancer and another Phase 3 study in hormone-sensitive prostate cancer. It is also being further developed in Phase 2 studies for the potential treatment of advanced breast cancer and hepatocellular carcinoma.

In addition, Medivation has a promising, wholly-owned, late-stage oncology pipeline, which includes two development-stage oncology assets, talazoparib and pidilizumab. Talazoparib, currently in a Phase 3 study for the treatment of BRCA-mutated breast cancer, has the potential to be a highly potent PARP inhibitor and could be efficacious across several additional tumors. Pidilizumab is an immuno-oncology (IO) asset being developed for diffuse large B-cell lymphoma and other hematologic malignancies and has the potential to be combined with IO therapies in Pfizer’s portfolio.

"We believe the combination with Pfizer is the right next step in our growth trajectory and is a testament to the passion and dedication by which the Medivation team has delivered on our mission to profoundly transform patients’ lives through medically innovative therapies," said David Hung, M.D., founder, president and CEO of Medivation. "This compelling transaction will deliver significant and immediate value to our stockholders and provides new opportunities for our employees as part of a larger company. We believe that Pfizer is the ideal partner to extend the reach of our blockbuster XTANDI franchise and take our promising, late-stage assets – talazoparib and pidiluzimab – to their next stages of development so that they can be made available to patients as quickly as possible."

"The proposed acquisition of Medivation will build upon Pfizer’s success with our IBRANCE (palbociclib) launch in HR+/HER2- metastatic breast cancer and with our strong immuno-oncology portfolio, and will transform Pfizer into a leading oncology company," said Albert Bourla, group president, Pfizer Innovative Health. "IBRANCE and XTANDI are anchor brands in breast and prostate cancer respectively, giving Pfizer leadership in two hormone-driven cancers. Similar to IBRANCE in the breast cancer setting, XTANDI is being explored for its potential to move from metastatic prostate cancer to treat earlier stages of non-metastatic prostate cancer. In addition, Medivation’s portfolio within prostate cancer and across diverse tumors will complement Pfizer’s broad IO portfolio. Finally, Medivation adds commercial scale to better compete with other top tier oncology companies in advance of the potential emergence of Pfizer’s IO pipeline expected in the next few years. Together, we believe Pfizer and Medivation can bring the full force of our combined research and resources to combat two of the most common cancers, as well as speed cures and make accessible breakthrough medicines to patients, redefining life with cancer."

Cancer remains the second leading cause of death in the U.S. and a "Top 10" killer worldwide. According to the American Cancer Society, breast cancer and prostate cancer are among the top three cancers by annual incidence in the U.S. There are several parallels between breast and prostate cancer, including the incidence of prostate cancer in the U.S., which is similar to that of breast cancer with approximately 280,000 cases per year.

Pfizer expects to finance the transaction with existing cash.

Under the terms of the merger agreement, a subsidiary of Pfizer will commence a cash tender offer to purchase all of the outstanding shares of Medivation common stock for $81.50 per share, net to the seller in cash, without interest, subject to any required withholding of taxes. The closing of the tender offer is subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of the outstanding shares of Medivation common stock. The merger agreement contemplates that Pfizer will acquire any shares of Medivation that are not tendered into the offer through a second-step merger, which will be completed promptly following the closing of the tender offer. Pfizer expects to complete the acquisition in the Third- or Fourth-Quarter 2016.

Pfizer’s financial advisors for the transaction were Guggenheim Securities and Centerview Partners, with Ropes & Gray LLP acting as its legal advisor. J.P. Morgan Securities and Evercore served as Medivation’s financial advisors, while Cooley LLP and Wachtell, Lipton, Rosen & Katz served as its legal advisors.

Interim Report for Kancera AB (publ) Q2 2016 January 1 – June 30, 2016

On August 19, 2016 Kancera reported results for Q2 2016 January 1 – June 30, 2016 (Press release, Kancera, AUG 19, 2016, View Source;releaseID=1182172 [SID:1234514645]).

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As a consequence of the acquisition of the subsidiary Kancera Förvaltning AB on 2016-06-16, the present Interim Report, Q2 2016, is prepared in accordance with IAS 34 and related parts of the Annual Accounts Act. The consolidated financial statements have been prepared in accordance with International Financial Reporting Standards (IFRS) as adopted by the EU and the Swedish Annual Accounts Act. The accounting of the parent company has been prepared in accordance with the Annual Accounts Act and the Swedish Financial Reporting Board’s recommendation RFR 2, including a number of new or revised standards, interpretations and improvements adopted by the EU and apply from 1 January 2016. The transition to the new accounting standards was voluntary and did not affect the income statement or balance sheet for the period January 1 – March 31, 2016 accounted for using the previous principles, or the comparison figures used below in the comments from the previous year regarding the parent company Kancera AB (for comparison between the accounting policies, see Note 1).

The period January to March 2016 in brief

R&D expenses for the period amounted to SEK 8.7m (SEK 8.8m) of which the second quarter constituted SEK 4.4m (SEK 4.6m).
Operating income for the period amounted to SEK -10.5m (SEK -10.4m) of which the second quarter constituted SEK -5.5m (SEK -5.4m).
Income after financial items for the period amounted to SEK -10.5m (SEK -10.3m) of which the second quarter constituted SEK -5.5m (SEK -5.4m).
Earnings per share for the period were SEK -0.10 (SEK -0.10) of which the second quarter constituted SEK -0.05 (SEK -0.05).
Cash flow from operating activities for the period amounted to SEK -9.4m (SEK -10.9m) of which the second quarter constituted SEK -3.1m (SEK -5.8m).
Equity as of June 30, 2016 amounted to SEK 71.1m (SEK 31.2m) or SEK 0.68 (SEK 0.30) per share. The equity/assets ratio as of June 30, 2016 was 86 percent (76 percent).
Cash and cash equivalents as of June 30, 2016 amounted to SEK 68.7m (SEK 25.4m). Unpaid share issue expenses amount to approximately SEK 2.2m.
Significant events during the period

Kancera has from the 1st of January 2016 extended the lease of the company’s laboratories within the Karolinska Science Park for three years through an agreement with Humlegården Fastigheter.
Kancera has provided an update of the small molecule patent portfolio.
– A patent covering small molecule PFKFB3 inhibitors has been approved in the USA.

– A patent application covering new chemical series in the HDAC6 project has been filed.

– An international patent application covering ROR inhibitors has been strengthened by adding examples of additional highly potent ROR inhibitors.

Kancera reported that the company has developed a new series of ROR inhibitors that show improved pharmaceutical properties which will allow preclinical studies of their effect on e.g. solid tumors. These results have prompted Kancera to concentrate the investments in the ROR project to small molecule inhibitors and terminate the product development of a ROR-based vaccine. Furthermore, Kancera reported results from the Fractalkine project showing that KAN0440567 after oral administration to mice effectively blocks the function of the Fractalkine receptor.
Kancera announced that the company according to plan has received another payment of about SEK 2.8 million in January, 2016 from the EU for the A-PARADDISE project, which aims to develop drugs against parasitic diseases.
Kancera reported that ROR inhibitors have been tested against human triple negative breast cancer transferred to zebra fish. The experiments showed that Kancera’s small molecule ROR inhibitors are able to both reduce tumor size and metastases (spread) of this aggressive tumor form. Further, Kancera reported that the company´s PFKFB3 inhibitors are active in the same model of triple negative breast cancer and that a patent application has been filed covering the discovery that PFKFB3 inhibitors enhance the effect of radiation treatment.
Kancera reported that the Company due to positive efficacy data in disease models of cancer and pain has decided to exercise the exclusive option to acquire the Fractalkine project. The acquisition will be carried out in connection with the completion of the ongoing transfer of results and know-how from Acturum and AstraZeneca to Kancera. Payment for the project to Acturum Life Science AB will be made into three steps by a total of 6 million shares, of which the first payment is due at the submission of the application for authorization of a clinical trial after an approval by Kancera´s shareholders. In parallel, the company intends to validate a broader use of the drug candidate (KAN0440567) in order to demonstrate its full commercial potential.
With the authorization of the extraordinary general meeting on 22 April 2016, Kancera AB carried out an issue of units with preferential rights for the shareholders, as well as an issue of units in the form of over-allotment space through a separate directed share issue without preferential rights. The rights issue, which was fully subscribed in May 2016, concerned 20,785,072 units and an over-allotment space of 4,000,000 units consisting of one share and one warrant at a price of SEK 2.50 per unit. On top of this compensation to underwriters and financial advisors was added. After registration of the issuance of the over-allotment option and compensation to underwriters and financial advisors, the number of shares in Kancera AB amounts to 131,486,720 and the number of warrants to 27 561 356. The new issue has brought Kancera AB approximately SEK 61.9 million before issue costs. The issue assets will be used for Kancera’s drug development, clinical studies and the further development of the Company’s capacity to commercialize products. The majority of Kancera’s resources are now concentrated on taking at least one of Kancera’s drug candidates in the ROR and Fractalkine projects to clinical trial for chronic lymphocytic leukemia and pancreatic cancer, respectively. In parallel, the Company intends to validate a broader use of the drug candidates from these projects in order to demonstrate their full commercial potential.
Kancera provided the following operational update of the fractalkine and ROR projects:
– the Fractalkine antagonist KAN0440567 is able to eliminate pain resulting from inflammation of the pancreas. This type of pain is similar to the pain resulting from cancer in the pancreas and therefore these results support the continued development of KAN0440567 towards clinical trials against cancer.

– the ROR inhibitor KAN0439834 has been shown to effectively kill resistant cancer cells from the bone marrow of multiple myeloma (MM) patients. MM originates in the bone marrow and is an incurable chronic disease today. Further studies are now focused on translating these findings to effects in animal models of MM which will provide a basis for decisions on future clinical trials evaluating Kancera’s ROR inhibitors.

Kancera AB announced that VINNOVA has paid an additional SEK 358,451 to the HDAC6 project as part of the grant totaling SEK 2 million which has been designated by VINNOVA for the further development of Kancera’s HDAC6 inhibitors against cancer. This payment was made following the approval of Kancera’s third progress report for the project.
Kancera AB hereby announces that its subsidiary Kancera Förvaltning AB has been formed. The operations of the subsidiary include mainly financial management including Kancera’s stock option plan.
Significant events after the end of the reporting period

Kancera AB has not reported any significant events after the end of the period.