On December 16, 2019 Mauna Kea Technologies (Paris:MKEA) (OTCQX:MKEAY) (Euronext: MKEA) inventor of Cellvizio, the multidisciplinary probe and needle-based confocal laser endomicroscopy (p/nCLE) platform, reported a strategic equity investment of 7.5 million euro by Johnson & Johnson Innovation – JJDC, Inc. (JJDC) (Press release, Mauna Kea Technologies, DEC 16, 2019, View Source [SID1234552405]). Pursuant to the agreement, JJDC, the strategic venture capital arm of Johnson & Johnson, will subscribe to 5,357,142 new ordinary MKEA shares for €1.40 per share, representing a total equity value of 7.5 million euro.

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"We are very proud to announce a strategic equity investment agreement with Johnson & Johnson Innovation – JJDC, Inc.," said Robert L. Gershon, Chief Executive Officer of Mauna Kea Technologies. "This agreement represents a significant strategic inflection point for Mauna Kea Technologies, particularly in that it provides a capital infusion that will help us execute our strategic growth initiatives."

Mr. Gershon continued: "This strategic investment will advance our collaboration with the Lung Cancer Initiative at Johnson & Johnson, which is working to develop new diagnostic and therapeutic approaches for this disease with significant unmet need. Our Cellvizio platform and AQ-Flex 19 Confocal Miniprobe (nCLE) is designed to be used through existing bronchoscopes, transbronchial needles and other bronchoscopic accessories, which makes it a viable option for use with the new emerging robotic and existing advanced navigation platforms."

Transaction Summary

JJDC will invest in the share capital of the Company an amount of 7.5 million euro, in consideration for 5,357,142 new ordinary shares, corresponding to an issue price per ordinary share equal to approximately €1.40. The new ordinary shares will be fungible with the existing shares of the Company. JJDC will own approximately 17.5% of the total ordinary shares outstanding following this transaction. JJDC will not have any board representation rights.

As part of the investment, JJDC agreed to customary lock up and stand still obligations for a period of 12 months. Pursuant to an agreement entered into as part of the investment, Mauna Kea has granted, for 24 months, to JJDC and its affiliates, a right of first refusal with respect to a transaction (other than change of control of Mauna Kea) on its pCLE (probe CLE) or nCLE (needle CLE) variants for use in endoluminal robotic procedures for lung applications and to the application of machine learning and artificial intelligence for lung applications. Mauna Kea has also granted, for 24 months, to JJDC and its affiliates, a right of first negotiation with respect to a transaction (other than change of control of Mauna Kea) on its pCLE (probe CLE) or nCLE (needle CLE) variants for use in endoluminal robotic procedures for GI and urology applications. In connection with this transaction, Piper Jaffray is acting as strategic advisor and McDermott Will & Emery is acting as legal advisor to Mauna Kea Technologies.

Use of proceeds

The Company’s management team expects that the net proceeds of the issue will be used to meet the financing needs of the current business in order to further develop the Cellvizio platform, pursue clinical studies and intensify sales and marketing efforts in the United States.

Cash position

The Company’s available cash position as of October 31, 2019 was approximately €4.1 million. Based on the Company’s current development plans, the Company expects the net proceeds from the share capital increase, combined with its current operating capital, to enable the funding of its operations until the end of 2020.

Legal framework

The new ordinary shares will be issued through a capital increase reserved to specified categories of person under the provisions of Article L. 225-138 of the French Commercial Code, pursuant to the decisions of the Company’s Board of Directors (Conseil d’Administration) dated December 13, 2019. Such decision by the Board of Directors is authorized pursuant to the 8th resolution adopted at the extraordinary meeting of the Company’s shareholders (Assemblée Générale Extraordinaire) held on October 5, 2018.

The closing of the transaction is expected to occur on December 19, 2019.

Application to list such new ordinary shares on the regulated market of Euronext Paris will be made pursuant to a listing prospectus subject to the approval by the Autorité des marchés financiers ("AMF") and comprising (i) the 2018 universal registration document, including the risk factors, which is expected to be filed with the AMF at the latest on December 17, 2019 (document d’enregistrement universel 2018), which will incorporate by reference the 2018 registration document (document de référence 2018) and the 2019 half-year financial report (rapport financier semestriel 2019), and (ii) a Securities Note (Note d’opération), including (iii) a summary of the prospectus. As from such filing with the AMF, copies of the Company’s 2018 universal registration document will be available free of charge at the Company’s head office located at 9 rue d’Enghien – 75010 Paris – France. The listing prospectus will be published on the AMF’s website at www.amf-france.org.

On December 16, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), reported that it has commenced an underwritten public offering of its common shares (the "Offering") (Press release, Aptose Biosciences, DEC 16, 2019, View Source [SID1234552390]). In addition, Aptose intends to grant the Underwriters a 30-day option to purchase up to an additional 15% of the common shares offered in the Offering. The Offering is subject to market and other conditions, and there can be no assurance as to whether or when the Offering may be completed, or as to the actual size or terms of the offering. All of the common shares to be sold in the proposed offering will be sold by the Company.

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Aptose intends to use all or a portion of the net proceeds to (i) accelerate and expand clinical trials for CG-806; (ii) accelerate and expand our clinical trials for APTO-253; (iii) acquire and fund (including through partnerships and in-licensing) additional clinical assets; and (iv) for working capital and general corporate purposes relating to (i), (ii) or (iii) above.

Piper Jaffray & Co. is acting as the sole active book-running manager and Canaccord Genuity is acting as passive book-running manager for the Offering.

No common shares will be offered or sold in Canada as part of this Offering. The Offering is subject to the approval of the Toronto Stock Exchange ("TSX") and Nasdaq. For the purposes of TSX approval, the Company is relying on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as Nasdaq.

The securities described above are being offered by Aptose pursuant to a shelf registration statement on Form S-3 (File. No. 333-230218), including a base prospectus, that was previously filed by Aptose with the Securities and Exchange Commission ("SEC") and declared effective on April 25, 2019. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. Before you invest, you should read the prospectus supplement and the accompanying prospectus and other documents the Company has filed with the SEC for more complete information about the Company and this offering. You may get these documents for free by visiting EDGAR on the SEC Web site at www.sec.gov. Alternatively, copies of the the prospectus supplement and the accompanying prospectus may be obtained, once available, from Piper Jaffray & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by email at [email protected] or by phone: 1-800-747-3924.

This press release does not constitute an offer to sell or the solicitation of offers to buy any securities of Aptose, and shall not constitute an offer, solicitation or sale of any security in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 16, 2019 Organovo Holdings, Inc. ("Organovo") (Nasdaq: ONVO) and Tarveda Therapeutics, Inc. ("Tarveda"), a privately-held, clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin miniature drug conjugates, reported that they have entered into a definitive merger agreement under which Tarveda would merge with a wholly-owned subsidiary of Organovo in an all-stock transaction (Press release, Organovo, DEC 16, 2019, View Source [SID1234552406]). Upon completion of the merger, the merged company would operate under the name Tarveda Therapeutics, Inc. and trade on the Nasdaq Stock Market LLC under the ticker symbol "TVDA."

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Tarveda is primarily focused on the development of its pipeline of Pentarin miniature drug conjugates designed to selectively accumulate and retain anti-cancer payloads in solid tumor malignancies. Following the closing of the merger, Tarveda intends to continue to focus on advancing its two clinical stage oncology programs, PEN-866 and PEN-221, and on further development of novel conjugates from its proprietary miniature drug conjugate platform. At the closing of the merger, it is estimated that the combined company will have approximately $35 million of cash on hand that is expected to provide sufficient funding into the second half of 2021 to achieve key upcoming clinical data milestones on both clinical programs.

"After completing an extensive and thorough review of strategic alternatives, we are extremely pleased to announce this transaction with Tarveda, which we believe is in the best interest for our stockholders," said Taylor J. Crouch, President and Chief Executive Officer, Organovo. "Tarveda is advancing an innovative pipeline of clinical stage cancer therapies derived from the company’s proprietary miniature drug conjugate platform. Tarveda is supported by a strong syndicate of investors including Novo A/S, Versant Ventures and ND Capital (NanoDimension) and a highly seasoned management team with prior public company experience."

"Our growing portfolio of miniature drug conjugates has the potential to represent much needed new treatment options for patients with solid tumor malignancies," said Drew Fromkin, President and Chief Executive Officer of Tarveda. "We are encouraged by the activity and tolerability demonstrated in Phase 1 human studies of our two clinical programs, PEN-866 and PEN-221. Our Pentarin miniature drug conjugates are designed to incorporate the best properties of small molecule drugs and antibody drug conjugates to form miniature drug conjugates that are effective at rapidly and deeply penetrating solid tumors while minimizing damage to healthy tissue. We are excited about this merger with Organovo and believe that this is the right point in Tarveda’s trajectory to move forward as a publicly traded company given several upcoming clinical data milestones that we expect to be achieved in 2020 and 2021."

Tarveda expects the merger to provide the capital required to advance its two lead programs through the next set of clinical milestones and to generate novel conjugates from its Heat Shock Protein 90 (HSP90) binding miniature drug conjugate platform. PEN-866, the initial clinical program from Tarveda’s HSP90 binding miniature drug conjugate platform, is designed to bind to the activated form of HSP90 in solid tumors to accumulate and retain its potent topoisomerase 1 inhibitor (SN-38) payload. PEN-866 is completing the Phase 1 dose escalation and safety portion of its "all comers" trial in various types of solid tumors and has shown to be well tolerated and demonstrated early clinical activity in heavily treated, advanced patients with a range of solid tumor malignancies. Beginning in early 2020, it is expected that PEN-866 will be evaluated in a Phase 2a study both as a single agent and as a combination therapy across a range of solid tumors that are sensitive to topoisomerase 1 inhibitors. PEN-221 is a miniature drug conjugate in clinical evaluation for the treatment of patients with solid tumors expressing somatostatin receptor 2 (SSTR2) on the cell surface and is linked to the potent tubulin inhibitor payload, DM1. In a Phase 1 study, PEN-221 was well tolerated and demonstrated early clinical activity. PEN-221 is currently being evaluated in a Phase 2a study for the treatment of patients with neuroendocrine tumors and small cell lung cancer.

About the Proposed Merger

Under the terms of the merger, it is anticipated that Tarveda stockholders will own approximately 75% of the combined company and current Organovo stockholders will own approximately 25% of the combined company on a fully-diluted basis. The exchange ratio is based on valuation assumptions for both companies subject to potential adjustments for certain financial metrics prior to the completion of the merger.

The transaction has been approved by the boards of directors of both companies. The merger is anticipated to close in the first quarter of 2020, subject to the approval of Organovo and Tarveda stockholders as well as other customary closing conditions.

Roth Capital Partners served as financial advisor, and Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP served as legal counsel to Organovo. Canaccord Genuity served as financial advisor, and Cooley LLP served as legal counsel, to Tarveda.

Management and Organization

Following the merger, the combined company will be led by the current Tarveda management team, including Drew Fromkin as President, Chief Executive Officer and Chairman; Jeffrey D. Bloss, M.D., Chief Medical Officer; Brian Roberts, Chief Financial Officer; Mark Bilodeau, Ph.D., Chief Scientific Officer; and Sudhakar Kadiyala Ph.D., Executive Vice President, Strategy.

The Board of Directors of the combined company will be comprised of eight directors, including six directors to be named by Tarveda and two directors to be named by Organovo. The corporate headquarters will be located in Watertown, MA.

Conference Call

Organovo and Tarveda will host a conference call at 8:30 a.m. ET on December 16, 2019, to discuss the proposed transaction. The conference call may be accessed by dialing (866) 405-4577 (domestic) or (602) 563-8680 (international) and using the conference ID 3679123. To help ensure the conference call begins in a timely manner, please dial in five minutes prior to the scheduled start time. The conference call will also be simultaneously webcast at View Source

Non-Solicitation

This communication does not constitute an offer to sell or solicitation of an offer to buy any securities, nor will there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

Important Information and Where to Find It

This communication may be deemed to be solicitation material in respect of the proposed transaction between Organovo and Tarveda. In connection with the proposed transaction, Organovo intends to file relevant materials with the SEC, including a registration statement on Form S-4 that will contain a proxy statement/prospectus/information statement. BEFORE MAKING ANY VOTING OR INVESTMENT DECISION, INVESTORS AND STOCKHOLDERS ARE URGED TO READ THESE MATERIALS CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTIONS. Stockholders may obtain, free of charge, copies of the definitive proxy statement and any other documents filed by Organovo with the SEC in connection with the proposed transactions at the SEC’s website (View Source) and at Organovo’s website.

Organovo and its directors and executive officers and Tarveda and its directors and executive officers may be deemed to be participants in the solicitation of proxies from the stockholders of Organovo in connection with the proposed transaction. Information regarding the special interests of these directors and executive officers in the merger will be included in the proxy statement/prospectus/information statement referred to above. Additional information regarding the directors and executive officers of Organovo is included in Organovo’s Definitive Proxy Statement on Schedule 14A relating to the 2019 Annual Meeting of Stockholders, filed with the SEC on July 26, 2019. This document is available free of charge at the SEC website (www.sec.gov) or at Organovo’s website.

On December 16, 2019 Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for XTANDI (enzalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) (Press release, Astellas, DEC 16, 2019, View Source [SID1234552391]). In 2019, it is estimated that just over 40,000 men in the United States are living with mCSPC, a form of prostate cancer that has spread to other parts of the body and still responds to a medical or surgical treatment that lowers testosterone.1,2,3

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With this approval, XTANDI is now the first and only oral treatment approved by the FDA in three distinct types of advanced prostate cancer – non-metastatic and metastatic castration-resistant prostate cancer (CRPC) and mCSPC. The approval is based on results from ARCHES, a randomized Phase 3 study which evaluated 1,150 men with mCSPC and met its primary endpoint of radiographic progression-free survival (rPFS).

"Men with metastatic castration-sensitive prostate cancer face complex treatment decisions and it is critical for physicians and patients to have as much information as possible when deciding on all of the options available," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers and lead investigator of ARCHES. "The research supporting the FDA approval and updated treatment guidelines provide physicians and patients with compelling evidence to consider enzalutamide as a treatment option for men with this disease."

Data from the ARCHES trial demonstrated that the use of XTANDI plus androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death by 61 percent compared to placebo plus ADT (n=1,150; hazard ratio [HR]: 0.39 [95% confidence interval (CI): 0.30-0.50]; p<0.0001). Overall survival data were not mature at the time of final rPFS analysis.

The safety analysis of the ARCHES trial is generally consistent with the safety profile of XTANDI in previous clinical trials in CRPC. In ARCHES, common adverse reactions (Grade 1 to 4 ARs; occurring in at least 5% of patients) that were reported more frequently in patients treated with XTANDI plus ADT vs placebo plus ADT included hot flush (27% vs 22%), asthenic conditions (24% vs 20%), hypertension (8.0% vs 5.6%), fractures (6.5% vs 4.2%), and musculoskeletal pain (6.3% vs 4.0%).

"XTANDI has been established as a standard of care for men with castration-resistant prostate cancer and has been prescribed to more than 420,000 patients worldwide since it was first approved in 2012," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas. "This approval in metastatic castration-sensitive prostate cancer means physicians can now offer XTANDI to men earlier in their advanced prostate cancer treatment journey."

"Today’s approval adds to over a decade of global clinical research aimed at better understanding the potential benefit of XTANDI for men with advanced prostate cancer," said Andy Schmeltz, Global President, Pfizer Oncology. "The FDA approval marks continued progress to help meet the needs of patients, including men living with metastatic castration-sensitive prostate cancer."

Pfizer and Astellas are committed to helping patients access XTANDI by providing them with access and reimbursement support resources, including information regarding patient healthcare coverage options and financial assistance options that may be available to help patients with financial needs. Patients can visit www.XTANDI.com or call XTANDI Support Solutions at 1-855-898-2634 to learn more.

About Metastatic Castration-Sensitive Prostate Cancer
Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as the bones, lymph nodes, bladder, and rectum.2 Men are considered castration- (or hormone-) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.1 The prevalence of mCSPC in the U.S. in 2019 is estimated to be just over 40,000.3

ARCHES Trial
The company-sponsored, Phase 3, randomized, double-blind, placebo-controlled, multi-national ARCHES trial (NCT02677896) enrolled 1,150 patients with mCSPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients in the trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy.

The primary endpoint of the trial was rPFS assessed by blinded independent central review. Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. Radiographic disease progression was defined by identification of two or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease. Patients were stratified by volume of disease (low vs high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, 1-5 cycles, or 6 prior cycles).

About XTANDI (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

Important Safety Information for XTANDI

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in seven randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in seven randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on XTANDI versus 0.7% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 10% of patients treated with XTANDI and in 4% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Adverse Reactions (ARs)
In the data from the four randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to adverse events (AEs) were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to AEs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AE as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher AEs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, and hypercalcemia.

Hypertension: In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of XTANDI patients and 5% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.

About the Enzalutamide Development Program
As part of Pfizer and Astellas’ ongoing commitment to the clinical development of enzalutamide, XTANDI is also being evaluated in the EMBARK trial, in men with high-risk non-metastatic CSPC. Details about EMBARK (NCT02319837) are available on www.clinicaltrials.gov.

The European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan are currently evaluating XTANDI for men with metastatic hormone-sensitive prostate cancer.

On December 16, 2019 NANOBIOTIX (Paris:NANO) (Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported receipt of the French 2019 Prix Galien Award for Most Innovative MedTech (Press release, Nanobiotix, DEC 16, 2019, View Source [SID1234552407]). The Company’s lead product, HENSIFY (NBTXR3) brand name for the treatment of locally advanced Soft Tissue Sarcoma (STS), was recognized after receiving European market approval (CE marking, DM class III, on April 2, 2019) earlier this year. The Prix Galien Award recognizes outstanding biomedical and medical technology product achievements that improve the human condition.

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HENSIFY is a first-in-class "radioenhancer" consisting of an aqueous suspension of crystalline hafnium oxide nanoparticles. The product is administered only once, directly into the tumor, before a patient’s first radiotherapy session. After intratumoral injection, the nanoparticles penetrate the tumor cells and, when activated by ionizing radiation, deliver a larger energy deposit within the tumor where the nanoparticles are present, thereby increasing the tumor-killing effect of treatment without increasing damage to surrounding healthy tissues. HENSIFY has a universal, physical mode of action and is inert within the human body outside of the presence of ionizing radiation.

The product is approved in Europe for the treatment of Soft Tissue Sarcoma (STS). Positive results from the Company’s phase III STS study were featured the August 2019 edition of The Lancet Oncology.

Moving forward, the Company is engaged in global clinical development of the product across fifteen (15) clinical trials in STS and other indications with a primary focus on global registration for the treatment of Head and Neck cancers. These trials include the expansion phase of a European phase I evaluating the safety and feasibility of NBTXR3 activated by radiation therapy(Study NBTXR3-102); an immuno-oncology (I/O) basket trial (Study NBTXR3-1100) which evaluates NBTXR3 in combination with anti-PD-1 in the United States (US); phase I trials evaluating NBTXR3 activated by radiation therapy for the treatment of liver and prostate cancer; a partnership with PharmaEngine in Asia evaluating NBTXR3 in combination with cisplatin; and a clinical collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) including nine (9) trials across several indications.

About the PRIX GALIEN

Created in France in 1970, the Prix Galien is the most prestigious award in the field of pharmaceutical research and innovation. Referred to as the "Nobel Prize of pharmaceutical research, it recognizes the efforts and achievements of pharmaceutical research and development.

About NBTXR3

NBTXR3 is a first-in-class product designed to destroy tumors through physical cell death when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide standards of radiation care. The physical mode of action of NBTXR3 makes it applicable across solid tumors such as lung, prostate, liver, glioblastoma, and breast cancers.

NBTXR3 is actively being evaluated in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or oropharynx in elderly and frail patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I/II trial regarding local control. In the United States, the company has started the regulatory process in regard to the clinical authorization to the phase II/III in locally advanced head and neck cancers.

Nanobiotix is also running an Immuno-Oncology development program. The Company received approval FDA to launch a clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 antibodies in locoregional recurrent (LRR) or recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) and lung or liver metastasis (mets) with HNSCC not amenable to re-irradiation or non-small cell lung cancer (NSCLC) as the primary tumor.

The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma. Furthermore, the company has a large-scale, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center (9 new phase I/II clinical trials in the United States) to evaluate NBTXR3 across head and neck, pancreatic, thoracic, lung, gastrointestinal and genitourinary cancers.