On May 24, 2018 Bristol-Myers Squibb Company (NYSE:BMY) reported it will hold an investor event on Monday, June 4, 2018 at 8:30 p.m. EDT (7:30 p.m. CDT) to discuss data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Press release, Bristol-Myers Squibb, MAY 24, 2018, View Source [SID1234526883]). Company executives will provide an overview of data presented from the company’s oncology portfolio, and address questions from investors and analysts.

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Investors and the general public are invited to listen to a live webcast of the event at investor.bms.com. Materials related to the event will be available at the same website prior to the event. A replay of the event will be available and can be accessed at investor.bms.com.

On May 24, 2018 Splash Pharmaceuticals, Inc. ("Splash"), a closely held private biopharmaceutical company that develops novel cancer therapies, reported the successful completion of the first safety cohort of patients and initiation of dose escalation in its ongoing clinical trial in platinum-resistant ovarian cancer patients (Press release, Splash Pharmaceuticals, MAY 24, 2018, View Source [SID1234526884]). The Phase I trial is being conducted at Rutgers Cancer Institute of New Jersey, a National Cancer Institute-designated Comprehensive Cancer Center.

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SPL-108 has been examined in multiple Phase I and II clinical trials in over 100 human subjects with documented clinical activity and excellent safety and tolerability. SPL-108 has also demonstrated significant activity in animal models for a variety of cancers including ovarian, breast, endometrial, prostate, liver and brain. The current clinical trial is testing the safety and efficacy of SPL-108 in conjunction with paclitaxel in platinum-resistant ovarian cancer patients.

"The target, mechanism of action, and clinical data all support the idea of further testing SPL-108 and paclitaxel in ovarian cancer patients," said Dr. David Nelson, President and CEO of Splash. "We believe that SPL-108 will be synergistic with other anti-tumor drugs as well and could be applicable in many different tumor types including breast and endometrial cancers. We are pleased that the first patients have cleared this critical safety hurdle."

"Ovarian cancer is often first diagnosed in advanced stages and treated with platinum-based chemotherapy. For many patients, their disease will become resistant to this treatment. As a researcher, I am happy to have an opportunity to translate the discoveries in my laboratory and use SPL-108 in the clinic to further identify much needed therapy alternatives for this population," said Dr. Lorna Rodriguez, Principal Investigator and Chief of the Gynecologic Oncology Program at Rutgers Cancer Institute.

On May 24, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI) (Karyopharm) and Antengene Corporation (Antengene), reported their entry into an exclusive license agreement for the development and commercialization of four of Karyopharm’s novel, oral drug candidates, including selinexor, Karyopharm’s lead SINE compound, eltanexor, Karyopharm’s second-generation SINE compound, verdinexor, Karyopharm’s lead compound in development for viral and other non-oncology indications, and KPT-9274, Karyopharm’s dual inhibitor of PAK4 and NAMPT (Press release, Karyopharm, MAY 24, 2018, View Source [SID1234526885]).The agreement includes the development and commercialization of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in China and Macau. The agreement also includes the development and commercialization of KPT-9274 in all human oncology indications and verdinexor in human non-oncology indications in mainland China, Macau, Taiwan, Hong Kong, South Korea, and the ASEAN countries.

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Under the terms of the agreement, Karyopharm will receive a one-time upfront payment of $12 million (USD) from Antengene. Karyopharm is eligible to receive up to an additional $150 million (USD) if certain future prespecified development, regulatory and commercial milestones are achieved by Antengene. Karyopharm is also eligible to receive tiered double-digit royalties based on future net sales of selinexor and eltanexor in China and Macau, and tiered single- to double-digit royalties based on future net sales of verdinexor and KPT-9274 in the relevant territories. In exchange, Antengene will receive exclusive rights to develop, manufacture and commercialize the compounds in the agreed to territories, at its own cost and expense. Antengene will also have the ability to participate in any global clinical study of selinexor, eltanexor, verdinexor or KPT-9274, and will bear the cost and expense for patients enrolled in clinical studies in the agreed to territories.

"This agreement with Karyopharm brings to our pipeline four promising, clinical-stage product candidates with broad applicability across multiple disease areas, with a particular focus in oncology, with the potential to help patients in a number of Asian territories. To complement the ongoing clinical development efforts by Karyopharm, Antengene may initiate additional clinical trials in diseases with high incidence in Greater China and other Asian regions," said Jay Mei, MD, PhD, Chairman and Chief Executive Officer of Antengene. "At Antengene, we are driven by a higher purpose and our goal is to become a market leader in developing innovative therapies that address unmet medical needs in the Asia Pacific region. We are delighted to partner with Karyopharm, a pioneering oncology company with a strong track record in the research and development of novel, targeted compounds, and we believe this transaction underscores our strong focus on and commitment to healthcare innovation."

"Antengene is dedicated to developing novel, cutting-edge therapies and has strong clinical and regulatory expertise and capabilities in China and the other licensed Asian regions," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "This strategic alliance adds to the impressive consortium of global Karyopharm partners who are actively advancing our novel oral drug candidates in these important markets, while allowing us to focus our internal resources on executing our late-phase selinexor trials and pursue regulatory approval in the United States and the European Union. In particular, this collaboration for additional territories in Asia complements our existing partnership with Ono Pharmaceutical for selinexor and eltanexor in Japan, Taiwan, South Korea, Hong Kong and the ASEAN countries."

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,400 patients have been treated with selinexor. In April 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the second half of 2018, with a request for accelerated approval for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON) and as a potential backbone therapy in combination with approved therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

About Eltanexor

Eltanexor is a second generation oral SINE compound. Eltanexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. Eltanexor has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects. A Phase 1/2 clinical study is currently ongoing evaluating eltanexor in myelodysplastic syndrome, colorectal cancer and castrate-resistant prostate cancer.

About Verdinexor

Verdinexor (KPT-335) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound being investigated across a variety of non-oncology indications in humans with an initial focus as a potential broad-spectrum treatment for viral diseases. Verdinexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), which is believed to be responsible for the movement of critical host cell and pathogen encoded cargoes across the nuclear membrane into the cytoplasm. Inhibition of this process with verdinexor results in accumulation of these cargoes in the nucleus, where they promote an anti-inflammatory state and prevent key steps in pathogen replication from occurring. Prior preclinical research showed efficacy of verdinexor in several viral models, including HIV and promising pre-clinical data has also been observed in multiple additional non-oncology indications. In a previously conducted randomized, double-blind, placebo-controlled, dose-escalating Phase 1 clinical trial in healthy human volunteers, verdinexor was found to be generally safe and well tolerated, with adverse events occurring in similar number and grade as placebo.

About KPT-9274

KPT-9274 is a first-in-class, orally bioavailable, small molecule immunometabolic modulator that works through non-competitive dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). NAMPT and NAPRT (Nicotinate Phosphoribosyltransferas) are the two main pathways for production of the NAD (nicotinamide dinucleotide). About 15-30% of all solid tumors are deficient in NAPRT, making them reliant on NAMPT for NAD production. Co-inhibition of PAK4 and NAMPT is believed to lead to synergistic anti-tumor effects through suppression of ß-catenin by blocking PAK4, leading to both immune cell activation and inhibition of tumor growth, blockade of DNA repair, cell cycle arrest, and energy depletion through NAMPT inhibition, and ultimately apoptosis. KPT-9274 may therefore have both immune-activating and direct antitumor effects. Tumors deficient in NAPRT may be particularly susceptible to KPT-9274’s actions. In contrast, normal cells are less sensitive to inhibition by KPT-9274 due in part to their relative genomic stability and lower metabolic demands. KPT-9274 is currently being evaluated in a Phase 1 clinical study in advanced solid tumors and non-Hodgkin’s lymphoma

On May 23, 2018 Sun Pharmaceutical Industries Ltd. (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715, "Sun Pharma" and includes its subsidiaries and/or associate companies) and Churchill Pharmaceuticals, LLC. (Churchill) reported that one of Sun Pharma’s wholly owned subsidiary companies has received approval from the U.S. Food and Drug Administration (FDA) for YONSA (abiraterone acetate), a novel formulation in combination with methylprednisolone, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Sun Pharma, 23 23, 2018, View Source [SID1234526869]).

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Churchill is eligible to receive upfront and sales-linked milestone payments, and royalties on sales from Sun Pharma pursuant to an agreement between the two companies to commercialize YONSA in the U.S.

"We are pleased to add YONSA to our growing oncology portfolio and continue to deliver on Sun Pharma’s commitment for enhanced patient access to innovative cancer therapies," said Abhay Gandhi, CEO – North America, Sun Pharma.

YONSA in combination with methylprednisolone was filed as a New Drug Application (NDA) under the 505(b)(2) regulatory pathway and will be promoted as a branded product in the U.S.

About YONSA (abiraterone acetate) tablets

YONSA is a CYP17 inhibitor which uses proprietary SoluMatrix Fine Particle Technology to create a micronized (smaller particle size) formulation of abiraterone acetate tablets – for the treatment of metastatic castration-resistant prostate cancer, in combination with methylprednisolone. The active ingredient is converted in vivo to abiraterone, an androgen biosynthesis inhibitor that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). The CYP17 enzyme is expressed in testicular, adrenal and prostatic tumor tissues and is required for androgen biosynthesis.

INDICATION

YONSA (abiraterone acetate) in combination with methylprednisolone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Administration Instructions

To avoid substitution errors and overdose, be aware that YONSA tablets may have different dosing and food effects than other abiraterone acetate products. Patients receiving YONSA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

YONSA can cause fetal harm and potential loss of pregnancy.

WARNINGS AND PRECAUTIONS

Hypertension, Hypokalemia, and Fluid Retention Due to Mineralocorticoid Excess: YONSA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with YONSA.

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. The safety of YONSA in patients with left ventricular ejection fraction < 50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) was not established because these patients were excluded from these randomized clinical trials.

Adrenocortical Insufficiency (AI): AI was reported in patients receiving abiraterone acetate in combination with corticosteroid, following an interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of AI, particularly if patients are withdrawn from corticosteroids, have corticosteroid dose reductions, or experience unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with YONSA. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity: In postmarketing experience, there have been abiraterone acetate-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths. Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with YONSA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced YONSA dose of 125 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt YONSA treatment and closely monitor liver function.

Re-treatment with YONSA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN.

Permanently discontinue treatment with abiraterone acetate for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

The safety of YONSA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

ADVERSE REACTIONS

The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

DRUG INTERACTIONS:

Based on in vitro data, YONSA is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during YONSA treatment. If a strong CYP3A4 inducer must be co-administered, increase the YONSA dosing frequency only during the co-administration period.

Abiraterone is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8.

Avoid coadministration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug.

In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with an abiraterone acetate single dose equivalent to YONSA 500 mg. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with abiraterone acetate.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential: Advise male patients with female partners of reproductive potential to use effective contraception.
Do not use YONSA in patients with baseline severe hepatic impairment (Child-Pugh Class C).
Please see Full Prescribing Information for YONSA at www.YonsaRx.com/Yonsa-pi

Disclaimer:

Statements in this "Document" describing the Company’s objectives, projections, estimates, expectations, plans or predictions or industry conditions or events may be "forward looking statements" within the meaning of applicable securities laws and regulations. Actual results, performance or achievements could differ materially from those expressed or implied.

On May 23, 2018 RenovoRx, Inc., a medical technology company developing an innovative catheter-based approach to treating pancreatic cancer, reported a $10 million financing round of which the company closed $7 million in an initial tranche (Press release, Renovorx, MAY 23, 2018, View Source [SID1234526870]). The round is led by Boston Scientific and joined by new investors including btov Partners and existing investors Astia Angels, the Angels’ Forum, the Halo Fund III, L.P., Golden Seeds, and Acorn Campus Taiwan.

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RenovoRx is developing a new approach to treating solid tumors – the RenovoCath System, a novel drug-device combination designed to deliver chemotherapy directly to tumors. The financing will be used to support ongoing product development and clinical trials of RenovoCath for the treatment of patients with locally advanced pancreatic cancer.

Pancreatic cancer is one of the deadliest types of cancer. Despite several FDA-approved treatments, it is projected to become the second-leading cause of cancer-related death in the United States around 20201, in part due to challenges in diagnosing and treating the disease. Pancreatic cancer is often not detected until it is advanced and considered inoperable. Standard treatments are often ineffective because they cannot be delivered directly to the tumor and are unable to penetrate the tumor tissue.

Based upon early studies of people with locally advanced pancreatic cancer and the potential to address a significant unmet need, the FDA recently granted RenovoCath an Orphan Drug Designation and approved an Investigational New Drug (IND) application for the company to advance directly to a pivotal Phase III clinical study.

"There are significant challenges in treating pancreatic cancer and our aim is to overcome these barriers by using a catheter-based, targeted approach to delivering chemotherapy. This funding, along with our FDA Orphan Drug Designation and approval of our IND are three important milestones in bringing this new therapy option to patients," said Shaun R. Bagai, CEO of RenovoRx. "We are excited to begin enrollment in our pivotal Phase III trial of the RenovoCath System and advance this technology in an area of significant patient need."

RenovoCath is a dual-balloon infusion catheter that reaches pancreatic tumors using a proprietary, catheter-based approach to deliver chemotherapy directly to the tumor inside the pancreas, without the need to identify blood vessels locally at the treatment site. An early feasibility study using this targeted approach suggested an improved survival benefit for people with advanced pancreatic cancer compared to historical controls.

Enrollment has begun in a randomized, Phase III study designed to compare intra-arterial chemotherapy via RenovoCath to systemic chemotherapy in approximately 300 patients with locally advanced pancreatic cancer at up to 20 sites across the United States. The primary endpoint is overall survival (OS) with secondary endpoints including safety and quality of life.