On April 5, 2019 UroGen Pharma Ltd. (Nasdaq: URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in uro-oncology, reported a new presentation from the pivotal Phase 3 OLYMPUS trial of UGN-101 (mitomycin gel) for instillation, an investigational formulation for the primary non-surgical treatment of patients with low-grade upper tract urothelial cancer (LG UTUC) (Press release, UroGen Pharma, APR 5, 2019, View Source [SID1234535020]). The analysis, which discusses the minimally invasive chemoablation approach of UGN-101 to potentially treat LG UTUC tumors, including those that are unresectable, will be presented on Sunday, May 5, 2019 in an oral presentation during the plenary session at the 114th American Urological Association (AUA) Annual Meeting in Chicago. The text for the abstract is available online through the Journal of Urology website.

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Details of AUA Oral Presentation
Abstract #: LBA-16
Session: Plenary Session, Next Frontier
Title: Nephron-sparing Management of Low Grade (LG) UTUC With UGN-101 (mitomycin gel) for Instillation: The Olympus Trial Experience
Presenter: Seth Paul Lerner, M.D., FACS, Professor of Urology, Baylor College of Medicine
Date and Time: Sunday, May 5, 2019; 3:17 – 3:26 PM CDT
Location: MCP: W375d

"The treatment of LG UTUC remains a technical challenge for urologists, given the anatomical complexity of the kidney and the physical limits of endoscopic instrumentation," said Mark P. Schoenberg, M.D., Chief Medical Officer of UroGen. "UroGen is committed to raising the standard of care for this typically elderly patient population whose current options consist of repetitive endoscopic surgical intervention or complete loss of a kidney. We look forward to presenting this UGN-101 analysis that further underscores the unmet need in patients with new and recurrent LG UTUC."

About UGN-101

UGN-101 (mitomycin gel) for instillation is an investigational drug formulation of mitomycin in Phase 3 development for the treatment of low-grade upper tract urothelial cancer (LG UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-101 is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-101 is delivered to patients using standard ureteral catheters. The Company initiated its rolling submission of the UGN-101 New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in December 2018. The FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to UGN-101 for the treatment of UTUC. If approved, UGN-101 would be the first drug approved for the non-surgical treatment of LG UTUC.

On April 5, 2019 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported that it has priced its concurrent underwritten public offerings of (i) 8,667,333 shares of its common stock and accompanying Class A warrants to purchase up to 1,951,844 shares of its common stock, at a combined price to the public of $7.50 per common share and accompanying Class A warrant and (ii) 666 shares of its Series A convertible preferred stock, which are convertible into 666,000 shares of its common stock, and accompanying Class A warrants to purchase up to 166,500 shares of its common stock, at a combined price to the public of $7,500 per Series A share and accompanying Class A warrant (Press release, Syros Pharmaceuticals, APR 5, 2019, View Source [SID1234535019]). Each Class A warrant will have an exercise price of $8.625 per share and will expire 3.5 years from the date of issuance. The Class A warrants sold in each offering will have the same terms. The gross proceeds of the offerings are expected to be approximately $70 million, prior to deducting the underwriting discounts and estimated offering expenses.

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The offerings are expected to close on or about April 9, 2019, subject to customary closing conditions.

Cowen and Piper Jaffray & Co. are acting as joint book-running managers for the offerings. JMP Securities is acting as lead manager and Roth Capital Partners is acting as co-manager.

The securities are being offered by Syros pursuant to a shelf registration statement that was filed with the Securities and Exchange Commission ("SEC") on July 20, 2017 and declared effective by the SEC on July 31, 2017. The offerings are being made only by means of the prospectuses and prospectus supplements that form a part of the registration statement.

Copies of the final prospectus supplements and the accompanying prospectuses relating to each offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies can also be obtained from Cowen and Company, LLC, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, or by telephone at (631) 274-2806; or Piper Jaffray & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, or by telephone: 800-747-3924, or by email: [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities 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 April 5, 2019 Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Medicines Agency (EMA) has granted priority drug status (PRIME) for experimental therapy at the JNJ -68284528 (JNJ-4528) on T cells carrying a chimeric antigen receptor (T-CAR) with B-cell maturation antigen (BCMA) (Press release, Johnson & Johnson, APR 5, 2019, View Source [SID1234535018]). The PRIME program simplifies interactions to optimize development and accelerate the evaluation of breakthrough scientific breakthroughs that address a critical medical need.

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"The PRIME status of this innovative CAR-T BCMA therapy illustrates the importance of regulatory innovation in the European Union," says Sjaak Bot, vice president of regulatory affairs for EMEA at Janssen. Biologics BV "We hope to be able to offer patients this significant breakthrough as quickly as possible. This PRIME status, the first obtained by Janssen, is an essential step towards a possible approval of marketing.

The PRIME status is based on the results of the LEGEND-2 Phase 1/2 study ( NCT03090659 ) evaluating CAR-T cells LCAR-B38M, sponsored by Nanjing Legend Biotech Co., 2 and on the CARTITUDE-1 study of Phase 1b / 2 ( NCT03548207 ) evaluating JNJ-4528, sponsored by Janssen and carried out in collaboration with Legend Biotech USA Inc. 3 The results of the LEGEND-2 study were presented at the 2018 annual conference of the American hematology (ASH) (Free ASH Whitepaper). 4 The results of the CARTITUDE-1 study will be presented shortly.

"CAR-T therapy is a promising therapeutic platform that builds on the patient’s immune system to attack tumor cells," says Sen Zhuang, MD, Ph.D., Janssen’s vice president of clinical oncology development. Research & Development, LLC. "We continue to advance this CAR-T therapy targeting BCMA through international clinical trials. We work tirelessly to be able to offer it to multiple myeloma patients around the world. "

JNJ-4528 is currently being evaluated for the treatment of patients with multiple myeloma who have previously followed at least three therapeutic regimens, containing a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 antibody, and who have presented progression of the disease within 12 months of the start of the most recent therapy, or being dual refractory to IMiD and proteasome inhibitor. 3 Patients have few therapeutic options, and often face an adverse prognosis. 5

In December 2017 , Janssen entered into a worldwide collaboration and license agreement with Legend Biotech to jointly develop and commercialize LCAR-B38M for the treatment of multiple myeloma. 6 In China, CARTIFAN-1 Phase 2 Confirmation Test ( NCT03758417 ), sponsored by Nanjing Legend Biotech Co. Ltd. and registered with the Center for Drug Evaluation (CTR20181007), is in the active recruitment phase to further evaluate LCAR-B38M in patients with relapsed or refractory multiple myeloma. 7

About LEGEND-2

LEGEND-2 ( NCT03090659 ) is an ongoing, open-label, single-group, Phase 1/2 study in four participating hospitals in China to evaluate the efficacy and safety of LCAR-B38M in the treatment of multiple myeloma recurrent or refractory. 2

About CAR-T and BCMA

CAR-T cells are an innovative approach to eradicating cancer cells by harnessing the power of the patient’s immune system. BCMA is a highly expressed protein in myeloma cells. 8 By targeting the BCMA via this approach, CAR-T therapies could redefine the multiple myeloma treatment paradigm.

About multiple myeloma

Multiple myeloma (MM) is an incurable blood cancer that originates in the bone marrow and is characterized by excessive proliferation of plasma cells. 9 In 2018, a diagnosis of MM was made in more than 48,200 people in Europe and more than 30,800 patients died. 10 For nearly 40 percent of patients with multiple myeloma, the survival rate is less than five years. 11

Although treatment may offer remission, recurrence is unfortunately very likely because there is currently no cure. 12 MM is refractory when the disease stops responding or progresses within 60 days of the patient’s last treatment. 13,14 Recurrent myeloma occurs when the disease recurs after a period of initial, partial or complete remission and can not be described as refractory. 15 While some MM patients have no symptoms, most of them are diagnosed because of symptoms that may include bone problems, low blood counts, elevated calcium levels, kidney problems or infections. 16 The prognosis for patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, is unfavorable. Few therapeutic options are available. 17

On April 5, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, taking a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported updated data following its presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Trovagene, APR 5, 2019, View Source;additional-patients-achieve-complete-response-at-two-highest-dose-levels-of-onvansertib-300825206.html [SID1234535017]). Additional data from its ongoing Phase 1b/2 study evaluating onvansertib in combination with standard-of-care chemotherapy in Acute Myeloid Leukemia (AML) demonstrates response to treatment in patients in the dose-escalation phase of the trial who received onvansertib at 27mg/m2 and 40mg/m2. The trial is now enrolling patients at the dose level of 60mg/m2 (approximately a 50% increase) in combination with either LDAC or decitabine.

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The greatest anti-leukemic activity, to-date, has been observed in the onvansertib + decitabine arm, now with 3 of 6 (50%) evaluable patients treated at the two highest dose levels tested to-date (27mg/m2 and 40mg/m2) achieving a complete response (2CR and 1CRi). The first patient in the onvansertib + LDAC arm has achieved a complete response at the highest dose level of 40mg/m2 of onvansertib.

"We are pleased with the response to treatment that we are seeing with onvansertib, as well as how safe and well tolerated it appears to be in this difficult-to-treat relapsed or refractory patient population," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "As we continue advancing our AML trial to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), we look forward to sharing additional readouts on the efficacy and safety of onvansertib and the potential opportunity to bring a much-needed new treatment option to relapsed or refractory AML patients."

About the Ongoing Onvansertib Phase 1b/2 Acute Myeloid Leukemia Trial

The Phase 1b/2 trial (NCT03303339) is a multi-center, open-label trial to evaluate the safety and efficacy of Onvansertib in combination with standard-of-care chemotherapy in AML patients who are ineligible for intensive induction therapy or whose disease is relapsed or refractory. In Phase 1b dose-escalation segment of the trial, the primary objective is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), using a traditional 3+3 design. In Phase 2 the MTD or RP2D will be administered to 32 patients to evaluate preliminary antitumor activity and to continue to evaluate the safety and tolerability of onvansertib in combination with standard-of-care chemotherapy. This trial is being led by Amer Zeidan, MBBS, MHS, assistant professor of Medicine at Yale School of Medicine, and Hematology expert at Yale Cancer Center, and Jorge Cortes, M.D., Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. The trial is being conducted at nine sites in the U.S.

About Onvansertib

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2. Trovagene has an ongoing Phase 1b/2 clinical trial with onvansertib in AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.

Onvansertib targets the PLK1 isoform, only (not PLK2 or PLK3), is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Colorectal Cancer, Triple Negative Breast Cancer (TNBC), as well as other types of cancer.

On April 5, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that Janssen Pharmaceutical K.K. has submitted a supplemental new drug application (sNDA) to the Ministry of Health, Labor and Welfare (MHLW) in Japan, for the use of daratumumab (DARZALEX) in combination with lenalidomide and dexamethasone (Rd) as treatment for patients newly diagnosed with multiple myeloma who are not candidates for high-dose chemotherapy and autologous stem cell transplant (ASCT) (Press release, Genmab, APR 5, 2019, View Source [SID1234535016]). The MHLW will grant a priority review of the application, based on the Orphan Drug Designation given to DARZALEX for patients with newly diagnosed multiple myeloma. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"This marks the third major regulatory submission based on the MAIA data, following similar submissions earlier this year in the U.S. and Europe. The regulatory approvals will make daratumumab plus lenalidomide and dexamethasone a viable option for newly diagnosed multiple myeloma patients in these three major markets," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The submission is based on data from the Phase III MAIA study of daratumumab in combination with Rd as treatment for patients newly diagnosed with multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from the study was presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which took place in San Diego, California in December 2018.

About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high-dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide is administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue Rd until disease progression or unacceptable toxicity. The primary endpoint of the study is PFS.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Approximately 6,313 new patients were expected to be diagnosed with multiple myeloma and approximately 4,338 people were expected to die from the disease in Japan in 2018.2 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.3 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.4

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).5,6,7,8,9

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.