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Genmab Announces Submission of Extension of Marketing Authorization to European Medicines Agency for Subcutaneous Formulation of Daratumumab

On July 19, 2019 Genmab A/S (CSE:GEN, Nasdaq:GMAB) reported that its licensing partner, Janssen Biotech, Inc., has submitted an application for the extension of the DARZALEX marketing authorization to the European Medicines Agency (EMA) (Press release, Genmab, JUL 19, 2019, View Source [SID1234537615]). This application seeks approval for the use of the subcutaneous (SubQ) formulation of daratumumab in multiple myeloma indications where the intravenous formulation of daratumumab is currently approved. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"Janssen has now submitted applications for approval of the subcutaneous formulation of daratumumab in both the U.S. and in Europe and we are looking forward to the possibility of multiple myeloma patients in both regions having access to this more convenient formulation of DARZALEX, which allows for both faster dosing and fewer infusion-related reactions according to recently presented data from the COLUMBA study," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The submission is based on data from two ongoing studies: the Phase III non-inferiority COLUMBA study, which is comparing the subcutaneous formulation of daratumumab to the intravenous formulation in patients with relapsed or refractory multiple myeloma and preliminary non-public data from the Phase II PLEIADES study, which is evaluating daratumumab in combination with certain standard multiple myeloma regimens. The topline results from the COLUMBA data were announced in February 2019 and subsequently presented in oral sessions at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 24th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

About the COLUMBA (MMY3012) study
The Phase III trial (NCT03277105) is a randomized, open-label, parallel assignment study that includes 522 adults diagnosed with relapsed and refractory multiple myeloma. Patients were randomized to receive either: SubQ daratumumab, as 1800 mg daratumumab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study; or 16 mg/kg IV daratumumab once weekly in Cycle 1 and 2, every two weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The co-primary endpoints of the study are overall response rate and Maximum trough concentration of daratumumab (Ctrough; defined as the serum pre-dose concentration of daratumumab on Cycle 3 Day 1).

About the PLEIADES (MMY2040) study
The Phase II trial (NCT03412565) is a non-randomized, open-label, parallel assignment study that includes 240 adults either newly diagnosed or with relapsed or refractory multiple myeloma. Patients with newly diagnosed multiple myeloma are being treated with 1,800 mg subcutaneous daratumumab in combination with either bortezomib, lenalidomide and dexamethasone (D-VRd) or bortezomib, melphalan and prednisone (D-VMP). Patients with relapsed or refractory multiple myeloma are being treated with 1,800 mg subcutaneous daratumumab plus lenalidomide and dexamethasone (D-Rd). An additional cohort of patients with relapsed and refractory multiple myeloma treated with daratumumab plus carfilzomib and dexamethasone (D-Kd) was subsequently added to the study. The primary endpoint for the D-VMP, D-Kd and D-Rd cohorts is overall response rate. The primary endpoint for the D-VRd cohort is very good partial response or better rate.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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.1 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 the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan.

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).1,2,3,4,5

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 refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

Atara Biotherapeutics Announces Pricing of $150.0 Million Public Offering

On July 19, 2019 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported the pricing of an underwritten public offering of 6,871,727 shares of its common stock at a price to the public of $15.28 per share (Press release, Atara Biotherapeutics, JUL 19, 2019, View Source [SID1234537614]). In addition, and in lieu of common stock, Atara Biotherapeutics is offering to certain investors pre-funded warrants to purchase 2,945,026 shares of its common stock at a purchase price of $15.2799 per pre-funded warrant, which represents the per share public offering price for the common stock, minus the $0.0001 per share exercise price of each such pre-funded warrant. The aggregate gross proceeds from the offering are expected to be approximately $150.0 million, before deducting the underwriting discounts and commissions and estimated offering expenses payable by Atara Biotherapeutics. The offering is expected to close on or about July 23, 2019, subject to customary closing conditions. In connection with the offering, Atara Biotherapeutics has granted the underwriters a 30-day option to purchase up to an additional 1,472,512 shares of its common stock at the public offering price, less the underwriting discounts and commissions.

Citigroup, Goldman Sachs & Co. LLC and Cowen are acting as joint book-running managers for the offering. Mizuho Securities and Canaccord Genuity are acting as co-managers.

The securities described above are being offered by Atara Biotherapeutics pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Atara Biotherapeutics with the Securities and Exchange Commission (the "SEC") and that became automatically effective on February 27, 2018. A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC, and a final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from: Citigroup, by mail at Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at 1-800-831-9146; Goldman Sachs & Co. LLC, by mail at Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at 1-866-471-2526, or by email at [email protected]; or Cowen, by mail at Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, by telephone at 1-631-592-5973, or by email at [email protected].

This press release shall 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 jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

Light Chain Bioscience – A brand of Novimmune SA

On July 18, 2019 NovImmune reported that it is excited to be launching the all new company website and branding (Press release, Light Chain Bioscience, JUL 18, 2019, View Source [SID1234573675]).

Following the successful divestment of EmaCo AG, a newly established company owning emapalumab and related assets to Sobi on 18 July 2019, NovImmune underwent major rebranding activities.

NovImmune SA will continue the successful legacy of 20+ years of antibody expertise and focus on its bispecific technology and associated programs and will rebrand as:

«Light Chain Bioscience – A brand of Novimmune SA»

The brand Light Chain Bioscience brings to life the research and development of novel multi-specific antibodies that rely on their light chain for their function.

A key distinctive feature of these multispecific antibodies is their native human structure, making them well tolerated and easy to develop.

Moleculin Announces Annamycin in Acute Myeloid Leukemia in Poland Advances to 3rd Cohort

On July 18, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported additional positive interim safety and efficacy data from its ongoing open label, single arm Phase 1/2 study of Annamycin in Poland (Press release, Moleculin, JUL 18, 2019, View Source [SID1234537617]). Three patients were treated at dose level of 150 mg/m2 with no drug-related adverse events, including no signs of cardiotoxicity. The results for all 3 patients were reviewed by the Drug Safety Review Committee, which determined that the trial could progress to the next higher dose level of 180 mg/m2. To date in Poland, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. One patient has completed treatment in the 120 mg/m2 (second) cohort in the Company’s parallel US clinical trial (the US trial started at a lower initial dose of 100 mg/m2).

"Recruitment in Poland continues to move rapidly," commented Walter Klemp, Moleculin’s Chairman and CEO. "And, moving beyond the 150 mg/m2 dosing level is quite significant, as the prior developer of Annamycin was unable to dose beyond this level. We remain optimistic that new methods for reducing the onset of mucositis (the dose limiting toxicity for Annamycin in prior clinical trials) will allow us to safely increase dosing to 180 mg/m2 or potentially even higher."

Mr. Klemp continued: "It’s also important to remind people that one of the advantages we believe Annamycin will offer is a lack of cardiotoxicity. We continue to see no evidence of cardiotoxicity in any of the patients treated thus far. We intend to advance the clinical study of Annamycin with the goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in both the US and European Union."

Study Design

The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. Both the US and Polish trials have the same study design, providing for a Phase 1 intended to establish a "Recommended Phase 2 Dose," ("RP2D") with cohorts of 3 patients each where the first cohort starts at a low beginning dose and each successive cohort receives the next higher dose level until "dose limiting toxicities" prevent further increases. In the case of cohort 1 in the US, one patient did not complete the evaluation protocol, so a fourth patient was added to complete that cohort.

A key difference in the US is that the starting dose was 100 mg/m2, whereas, in Poland, the starting dose was 120 mg/m2. Having completed the first cohort in the US, the Company is seeking patients for the second cohort at a dose level of 120 mg/m2 and 1 of the 3 patients required to fill the cohort has now been treated. Now that 3 patients have completed the safety evaluation period of the second cohort in Poland,

the third cohort will begin there at a dose level of 180 mg/m2. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial will assist in the FDA’s review of cardiac safety.

Atara Biotherapeutics Announces Proposed Offering of Common Stock

On July 18, 2019 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that it has commenced an underwritten public offering of $125,000,000 of shares of its common stock (Press release, Atara Biotherapeutics, JUL 18, 2019, View Source [SID1234537613]). In connection with the proposed offering, Atara Biotherapeutics expects to grant the underwriters a 30-day option to purchase up to an additional $18,750,000 of shares of its common stock at the public offering price, less the underwriting discounts and commissions. All of the shares in the proposed offering will be sold by Atara Biotherapeutics. The proposed offering is subject to market and other conditions, and there can be no assurances as to whether or when the proposed offering may be completed, or as to the actual size or terms of the proposed offering.

Citigroup, Goldman Sachs & Co. LLC and Cowen are acting as joint book-running managers for the proposed offering. Mizuho Securities and Canaccord Genuity are acting as co-managers.

The shares described above are being offered by Atara Biotherapeutics pursuant to a shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Atara Biotherapeutics with the Securities and Exchange Commission (the "SEC") and that became automatically effective on February 27, 2018. A preliminary prospectus supplement and accompanying prospectus relating to the proposed offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the proposed offering, when available, may be obtained from: Citigroup, by mail at Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at 1-800-831-9146; Goldman Sachs & Co. LLC, by mail at Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at 1-866-471-2526, or by email at [email protected]; or Cowen, by mail at Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, by telephone at 1-631-592-5973, or by email at [email protected]. The final terms of the proposed offering will be disclosed in a final prospectus supplement to be filed with the SEC.