On May 26, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an innovation-driven pharmaceutical company, reported it will host an investor conference call to discuss detailed results from the pivotal, Phase 3 BOSTON study evaluating once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy (Press release, Karyopharm, MAY 26, 2020, View Source [SID1234558443]). The conference call will follow the presentation of this data at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program. The investor conference call is scheduled for Friday, May 29, 2020 at 1:00 p.m. ET.

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As previously reported, the BOSTON study met its primary endpoint with a significant increase in progression-free survival in patients with multiple myeloma following one to three prior lines of therapy.

Details for the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program presentation are as follows:

Late-breaking Oral Presentation

Title: Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Patients with Multiple Myeloma (MM) After 1-3 Prior Therapies: Initial Results of the Phase 3 BOSTON
Presenter: Meletios A. Dimopoulos, National and Kapodistrian University of Athens School of Medicine
Abstract #: 8501
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Date and time: Friday, May 29, 2020, 8:00 a.m. – 11:00 a.m.
URL: View Source

Conference Call Information

Karyopharm will host a conference call Friday, May 29, 2020, at 1:00 p.m. Eastern Time, to discuss the detailed Phase 3 BOSTON study results. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 2049236. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor. A supplemental New Drug Application was accepted by the FDA seeking accelerated approval for selinexor as a new treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and selinexor has received Fast Track and Orphan designation and Priority Review from the FDA with a scheduled PDUFA date of June 23, 2020 for this patient population. 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), for which Karyopharm announced positive top-line results in March 2020. In May 2020, Karyopharm submitted a supplemental New Drug Application based on data from the Phase 3 BOSTON study. Additional, ongoing trials for selinexor include as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and 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 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.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

IMPORTANT SAFETY INFORMATION

Thrombocytopenia

XPOVIO can cause thrombocytopenia, leading to potentially fatal hemorrhage. Thrombocytopenia was reported as an adverse reaction in 74% of patients, and severe (Grade 3-4) thrombocytopenia occurred in 61% of patients treated with XPOVIO. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, clinically significant bleeding occurred in 5% of patients with thrombocytopenia and fatal hemorrhage occurred in <1% of patients.

Monitor platelet counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.

Neutropenia

XPOVIO can cause neutropenia, potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients, and severe (Grade 3-4) neutropenia occurred in 21% of patients treated with XPOVIO. The median time to onset of the first event was 25 days. Febrile neutropenia was reported in 3% of patients.

Obtain neutrophil counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures including antimicrobials for signs of infection and use of growth factors (e.g., G-CSF). Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.

Gastrointestinal Toxicity

Gastrointestinal toxicities occurred in patients treated with XPOVIO.

Nausea/Vomiting

Nausea was reported as an adverse reaction in 72% of patients, and Grade 3 nausea occurred in 9% of patients treated with XPOVIO. The median time to onset of the first nausea event was 3 days.

Vomiting was reported in 41% of patients, and Grade 3 vomiting occurred in 4% of patients treated with XPOVIO. The median time to onset of the first vomiting event was 5 days.

Provide prophylactic 5-HT3 antagonists and/or other anti-nausea agents, prior to and during treatment with XPOVIO. Manage nausea/vomiting by dose interruption, reduction, and/or discontinuation. Administer intravenous fluids and replace electrolytes to prevent dehydration in patients at risk. Use additional anti-nausea medications as clinically indicated.

Diarrhea

Diarrhea was reported as an adverse reaction in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients treated with XPOVIO. The median time to onset of diarrhea was 15 days.

Manage diarrhea by dose modifications and/or standard anti-diarrheal agents; administer intravenous fluids to prevent dehydration in patients at risk.

Anorexia/Weight Loss

Anorexia was reported as an adverse reaction in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. The median time to onset of anorexia was 8 days.

Weight loss was reported as an adverse reaction in 47% of patients, and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days.

Monitor patient weight at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Manage anorexia and weight loss with dose modifications, appetite stimulants, and nutritional support.

Hyponatremia

XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO experienced hyponatremia, 22% of patients experienced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.

Monitor sodium level at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clinical guidelines (intravenous saline and/or salt tablets), including dietary review. Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.

Infections

In patients receiving XPOVIO, 52% of patients experienced any grade of infection. Upper respiratory tract infection of any grade occurred in 21%, pneumonia in 13%, and sepsis in 6% of patients. Grade ≥3 infections were reported in 25% of patients, and deaths resulting from an infection occurred in 4% of patients. The most commonly reported Grade ≥3 infections were pneumonia in 9% of patients, followed by sepsis in 6%. The median time to onset was 54 days for pneumonia and 42 days for sepsis. Most infections were not associated with neutropenia and were caused by non-opportunistic organisms.

Neurological Toxicity

Neurological toxicities occurred in patients treated with XPOVIO.

Neurological adverse reactions including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state) occurred in 30% of patients, and severe events (Grade 3-4) occurred in 9% of patients treated with XPOVIO. Median time to the first event was 15 days.

Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes.

Embryo-Fetal Toxicity

Based on data from animal studies and its mechanism of action, XPOVIO can cause fetal harm when administered to a pregnant woman. Selinexor administration to pregnant animals during organogenesis resulted in structural abnormalities and alterations to growth at exposures below those occurring clinically at the recommended dose.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥20%) are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The treatment discontinuation rate due to adverse reactions was 27%; 53% of patients had a reduction in the XPOVIO dose, and 65.3% had the dose of XPOVIO interrupted. The most frequent adverse reactions requiring permanent discontinuation in 4% or greater of patients who received XPOVIO included fatigue, nausea, and thrombocytopenia. The rate of fatal adverse reactions was 8.9%.

On May 26, 2020 Exact Sciences Corp. (Nasdaq: EXAS) reported that company management will participate in the following conferences and invited investors to participate by webcast (Press release, Exact Sciences, MAY 26, 2020, View Source [SID1234558442]).

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Jefferies 2020 Healthcare Conference
Fireside Chat on Tuesday, June 2, 2020, at 2:30 p.m. EDT
William Blair 2020 Growth Stock Conference
Fireside Chat on Tuesday, June 9, 2020, at 3:40 p.m. EDT
The webcast can be accessed in the investor relations section of Exact Sciences’ website at www.exactsciences.com.

On May 26, 2020 Evogene Ltd. (NASDAQ: EVGN, TASE: EVGN.TA), a leading computational biology company targeting to revolutionize life-science product development across several market segments, reported its financial results for the first quarter, ended March 31, 2020 (Press release, Evogene, MAY 26, 2020, View Source [SID1234558441]).

Ofer Haviv, Evogene’s President and CEO, stated: "I would like to update that during the COVID-19 pandemic, the company and its employees have been working in compliance with the guidelines provided by the Israeli health authorities to ensure the health and safety of our employees. I would like to thank our employees for their great efforts and commitment during this period of time. I am pleased to share that Evogene’s operations were not significantly impacted and that, as of today, we have almost resumed full activity, in line with the official guidelines. The company has taken certain steps to strengthen its ability to withstand the impact of COVID-19 and I am pleased to share that, as of today, we have not found it necessary to change any of our main targets and goals for 2020 and we have even succeeded in decreasing our cash burn rate forecast for the year.

"Last week, we unveiled Evogene’s new branding, which we believe reflects the company’s expanded vision and new business model and will facilitate clearer communications with potential partners and investors. This re-branding is the outcome of an evolution the company underwent in recent years that led Evogene to broaden its vision beyond plant genomics and focus on new target markets outside of agriculture.

"Established as a spin-off from Compugen in 2002, Evogene was initially focused on applying its capabilities in computational biology in agriculture and more specifically, on improving seed traits via genomic modification. This focus shifted following changes in this market and in consumer tastes that led Evogene to broaden its vision and focus on several new target markets.

"In the past years, management took a series of steps that paved the path to its new value proposition. Two key decisions underlay this development; the first was expanding Evogene’s technological capabilities in computational biology to include the development of products based on microbes and small molecules, in addition to genomics, and the second was to expand Evogene’s focus in and beyond agriculture, to human health.

"These decisions led to the creation of the two main pillars of our new offering – our computational biology technology, the CPB platform, and our rapidly growing subsidiaries.

"With respect to the CPB platform, a deep understanding of biology, combined with disruptive computational technologies, including artificial intelligence and big data, have led to the birth of this powerful platform. The platform provides tailor-made solutions for the discovery and development of products based on microbes, small molecules and genetic elements for life-science based industries, including: human health, agriculture and industrial applications. With these new capabilities, we are ready to engage with world leading companies across diverse market segments focusing on different product types.
"Before elaborating on our subsidiaries, I would like to note that in parallel to the establishment of our powerful technology, we utilized the CPB platform in certain market segments to internally build product pipelines. The subsidiaries established over the past few years were built on these internal product pipelines to advance existing and future product candidates towards commercialization in a defined market segment, using the CPB platform through an exclusive license for its field. Each subsidiary may decide to develop and commercialize its products independently or through strategic collaborations.

"It is important for me to note, that each subsidiary has several upcoming milestones, which mark their development roadmap and these can be viewed in the presentation filed last week. I am happy to share that during the first quarter of 2020 AgPlenus reached one of these milestones with the announcement of their collaboration with Corteva for the co-development of new Mode-of-Action herbicides, based on herbicidal candidates discovered by AgPlenus. We see this collaboration to hold great promise." – Continued Mr. Haviv.

Additional announcements made by subsidiaries during the first quarter of 2020:

Biomica entered an agreement with Biose Industrie for scale-up and GMP production of drug candidates BMC121 & BMC127 for its immuno-oncology program, which is intended to support the preparation towards anticipated first-in-man proof-of-concept clinical trials.

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Canonic entered into an agreement with Hadassah Medical Center for pre-clinical studies to support the development of Canonic’s medical cannabis products, focusing on inflammatory indications at Prof. Reuven Or’s laboratory.
"I am very pleased with the progress we’ve made so far as a company and am confident that we have a solid strategy that will prove fruitful over the next few years. We will continue to develop the CPB platform and each subsidiary will be accountable to their milestones, while at the same time we will support them in any way possible. We are ready to continue to harness our technology, forging new strategic partnerships, and to benefit as a shareholder from our subsidiaries as their value is unlocked and becomes increasingly apparent." – Mr. Haviv concluded.

Evogene’s new investor presentation can be viewed at: www.evogene.com

Consolidated financial results for the period ending March 31, 2020:

Cash usage: For the full year of 2020, the company has provided an update on its estimated cash usage, excluding cash usage of Lavie Bio, from the range of $14-$16 million to $13-$15 million. The expected decrease in cash usage is due to adjustments in the company’s expenditures to better accommodate the impact of COVID-19, including a temporary reduction in salary-based expenditures and a cut-back in secondary activities that are not directly connected to the company’s near-term milestones, as well as an expected increase in revenues for the remainder of 2020, following the collaboration agreement AgPlenus signed with Corteva in March 2020. Reduced cash usage is expected to begin to take effect in the results of the second quarter of 2020.

Cash position: As of March 31, 2020, Evogene had approximately $40.6 million in consolidated net cash, short-term bank deposits and marketable securities. Approximately $16 million of Evogene’s consolidated cash is attributed to its subsidiary, Lavie Bio. The company’s consolidated cash usage amounted to $6.3 million during the first quarter of 2020. Excluding the cash usage of Lavie Bio, the company’s cash usage amounted to $4.6 million during the first quarter of 2020. Cash usage during the first quarter of 2020 included pre-paid expenses and non-recurring payments of approximately $0.8 million.

Evogene does not have bank debt.

Revenues for the first quarter of 2020, were $0.1 million versus $0.3 million in the same period the previous year. Revenues primarily consist of third-party research and development payments. These revenues represent R&D cost reimbursement and milestone payments under our various collaboration agreements. The majority of these agreements also provide for royalties or other forms of revenue sharing from successfully developed products.

Gross profit for the first quarter of 2020 was $36 thousand in comparison to $277 thousand in the first quarter of 2019.

R&D expenses for the first quarter of 2020 were $4.6 million (including a non-cash expense of $0.9 million for amortization of share-based compensation), in comparison to $3.5 million (including a non-cash expense of $0.1 million for amortization of share-based compensation) in the first quarter of 2019. R&D expenses in this quarter were attributed to product development activities of the Company and its subsidiaries, including fermentation, lab work and pre-clinical studies carried out by third parties as well as expenses relating to computational work.

Business Development (BD) expenses for the first quarter of 2020 were $1 million (including a non-cash expense of $0.7 million for amortization of share-based compensation), in comparison to $0.5 million (including a non-cash expense of $0.1 million for amortization of share-based compensation) in the first quarter of 2019.

G&A expenses for the first quarter of 2020 were $1.3 million (including a non-cash expense of $0.3 million for amortization of share-based compensation), in comparison to $0.9 million (including a non-cash expense of $31 thousand for amortization of share-based compensation) in the first quarter of 2019.

Operating loss for the first quarter of 2020 was $ 6.9 million (including a non-cash expense of $1.9 million for amortization of share-based compensation), in comparison to $ 4.7 million (including a non-cash expense of $0.2 million for amortization of share-based compensation) in the first quarter of 2019. This is mainly due to an increase of $1.7 million in non-cash expenses related to the amortization of share-based compensation, mainly attributed to options granted to Lavie Bio employees.

Net financing expenses for the first quarter of 2020 were $0.4 million in comparison to net financing income of $0.9 million in the first quarter of 2019. The increase in the net financing expenses during the quarter is due to the translation of Israeli Shekel denominated cash and marketable securities to U.S. Dollars.

Loss for the first quarter of 2020 was $7.2 million in comparison to a loss of $3.8 million during first quarter of 2019. The increase in loss is attributed to an increase of $1.7 million in non-cash expenses related to the amortization of share-based compensation, as described above, and to net financing expenses in comparison to net financing income in the first quarter of 2019.

On May 26, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) and BeiGene, Ltd. ("BeiGene") (Nasdaq: BGNE; HKEX: 06160) reported that they have entered into a clinical collaboration agreement to evaluate the safety, tolerability and efficacy of combining two of Chi-Med’s drug candidates, surufatinib and fruquintinib, with BeiGene’s anti-PD-1 antibody tislelizumab, for the treatment of various solid tumor cancers, in the U.S., Europe, China and Australia (Press release, Hutchison China MediTech, MAY 26, 2020, https://www.chi-med.com/chi-med-and-beigene-collaboration-to-evaluate-surufatinib-and-fruquintinib-with-tislelizumab-combinations/ [SID1234558440]).

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Under the terms of the agreement, Chi-Med and BeiGene each plan to explore development of the combination of surufatinib with tislelizumab or fruquintinib with tislelizumab in different indications and regions. The companies have agreed to provide mutual drug supply and other support.

"We are very pleased to enter into this clinical collaboration with BeiGene, a company with which we share a vision to discover, develop and commercialize innovative targeted therapies and immunotherapies worldwide," said Dr. Marek Kania, Senior Vice President and Chief Medical Officer, Hutchison MediPharma International.[1]

"By working together with a partner like Chi-Med, we hope to understand and develop innovative combination therapies that may bring meaningful treatments to cancer patients around the world. Through this collaboration we plan to further evaluate tislelizumab in combination with oral VEGFR inhibitors to target a variety of solid tumor cancers," said Lai Wang, Ph.D., Senior Vice President, Head of Global Research, Clinical Operations & Biometrics and APAC Clinical Development, at BeiGene.

Each of these three compounds are currently in late-stage global clinical development across many countries outside of China. Tislelizumab is a humanized IgG4 anti-programmed death-1 ("PD-1") monoclonal antibody specifically designed to minimize binding to Fc receptor gamma ("FcγR"), which is believed to play an essential role in activating phagocytosis in macrophages, to minimize its negative impact on T effector cells. Fruquintinib is designed to improve kinase selectivity against vascular endothelial growth factor receptors ("VEGFR") in order to minimize off-target toxicities, and thereby provide consistent coverage and better tolerability, which is very important in combinations. Surufatinib, a VEGFR inhibitor, inhibits colony stimulating factor-1 receptor ("CSF-1R") additionally, thereby blocking the accumulation of tumor associated macrophages and promoting infiltration of T effector cells into tumors, leading to possible synergistic anti-tumor activity with PD-1 inhibitors.

Tislelizumab and fruquintinib have both been approved by the China National Medical Products Administration ("NMPA"), which is also currently reviewing the New Drug Application ("NDA") for surufatinib that was submitted late last year.

About Tislelizumab
Tislelizumab (BGB-A317) is a humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

Tislelizumab is approved by the China NMPA as a treatment for patients with classical Hodgkin’s lymphoma ("cHL") who received at least two prior therapies and for patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Currently, 15 potentially registration-enabling clinical trials are being conducted in China and globally, including 11 Phase 3 trials and four pivotal Phase 2 trials.

Tislelizumab is not approved for use outside of China.

About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR 1/2/3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may be highly suitable for combinations with other anti-cancer therapies.

Fruquintinib was approved for marketing in China by the NMPA in September 2018 and commercially launched by Eli Lilly and Company ("Lilly") in late November 2018 under the brand name Elunate. Elunate is for the treatment of patients with metastatic colorectal cancer that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with colorectal cancer ("CRC") in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).

Chi-Med retains all rights to fruquintinib outside of China and is partnered with Lilly in China.

Global development of fruquintinib in CRC: We intend to initiate a Phase III registration study, known as the FRESCO-2 study, in the U.S., Europe and Japan in CRC. FRESCO-2 is expected to start enrolling patients in mid-2020. Based on our agreement with the U.S. Food and Drug Administration (FDA), the FRESCO and FRESCO-2 studies, if positive, could support our NDA application.

Gastric Cancer in China: In October 2017, we initiated the FRUTIGA study, a randomized, double-blind, Phase III study in China to evaluate the efficacy and safety of fruquintinib combined with paclitaxel (Taxol) compared with paclitaxel monotherapy in the treatment of patients with advanced gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier: NCT03223376). Over 540 patients are expected to be enrolled into the FRUTIGA study at a 1:1 ratio with the primary endpoint of this study being overall survival (OS). In April 2019, we conducted the first interim analysis of the FRUTIGA study for futility. Following the analysis of safety and efficacy of the first 100 patients, the Independent Data Monitoring Committee ("IDMC") recommended to continue the study without changes. We expect to conduct a second interim analysis in mid-2020 and complete enrollment of the study in 2020.

Immunotherapy combinations: In November 2018, we entered into two collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with Tyvyt (sintilimab) and geptanolimab (GB226, genolimzumab).

Fruquintinib is not approved for use outside of China.

About Surufatinib
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and CSF-1R, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Chi-Med currently retains all rights to surufatinib worldwide.

Neuroendocrine tumors ("NET") in the U.S., Europe and Japan: We are preparing for regulatory interactions in the U.S., Europe and Japan to confirm clinical development and path to registration, based on the robust data from the two positive Phase III studies of surufatinib in NET in China, and the ongoing multi-cohort Phase Ib study in the U.S. (clinicaltrials.gov identifier: NCT02549937). In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019.

Non-pancreatic neuroendocrine tumors in China: In November 2019, a New Drug Application ("NDA") for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the China NMPA and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic patients in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the IDMC to determine that the study met the pre-defined primary endpoint of progression-free survival ("PFS") and should be stopped early. The positive results of this trial were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress (clinicaltrials.gov identifier: NCT02588170).

Pancreatic neuroendocrine tumors in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET is being prepared for submission, following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821). Study results will be submitted for presentation at an upcoming scientific conference.

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival ("OS") (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: In November 2018 and September 2019, we entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with Tuoyi (toripalimab) and Tyvyt, which are approved in China.

On May 26, 2020 FUJIFILM Corporation (President: Kenji Sukeno) reported that it will collaborate with Merck & Co., Inc., Kenilworth, N.J., U.S.A. (NYSE: MRK), known as MSD outside the United States and Canada (Press release, Fujifilm, MAY 26, 2020, View Source [SID1234558439]). It signed a clinical collaboration agreement with MSD International GmbH, effective May 25, for the implementation of a clinical trial that evaluates a combination therapy with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, and Fujifilm’s drug candidate FF-10832, a liposome drug candidate. The liposome formulation is designed to utilize drug delivery system (DDS) technology to deliver drugs to affected sites.

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Based on this agreement, Fujifilm plans to initiate a U.S. clinical trial in the fiscal year 2020 ending March 2021 to evaluate combination therapy using its FF-10832, a liposome formulation drug candidate, and KEYTRUDA (pembrolizumab). The goal of the study will be to confirm the combination tolerability, pharmacokinetics and preliminary estimates of clinical activity of FF-10832 with Keytruda in selected tumor types.

A liposome formulation is a preparation that encapsulates active ingredients in liposomes, which are artificially constructed vesicles made from an organic substance such as phospholipids which make up cell and biological membranes. Liposomes are expected to deliver active ingredients efficiently to affected sites.

Fujifilm’s drug candidate, FF-10832, is a liposome formulation which encapsulates gemcitabine*, an approved anti-cancer agent indicated for the treatment of a variety of solid tumors including pancreatic cancer. The clinical phase I study of FF-10832 targeting advanced solid tumors is currently underway in the U.S. Preclinical studies in mice have demonstrated that a combination** of FF-10832 and immune checkpoint inhibitors increased CD8-positive cytotoxic T cells***, leading to longer survival compared to monotherapy.

Fujifilm will leverage its established proprietary technologies to tackle the development of new drugs responding to unmet medical needs, and also develop new DDS technologies, thereby creating new value and enhancing medical care worldwide.

*An anti-cancer agent developed by Eli Lilly and Company (generic name: gemcitabine; brand name: Gemzar). It is used as the first-line drug for pancreatic cancer, and is also being used for treating a wide range of other cancers such as lung and ovarian cancers.
**Combined administration of FF-10832 and anti-CTLA-4 antibody. Anti CTLA-4 antibody and anti PD-1 antibody are immune checkpoint inhibitors which inhibit the mechanism that weakens the actions of immune cells ("immune checkpoint") and activated immune cells attack cancer cells.
***A type of T-cell that makes immune responses. It recognizes cells that become a foreign body to the host, and destroys them.