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Genmab Announces Positive Topline Results in Phase III Study of Daratumumab in Combination with Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma

On September 13, 2019 Genmab A/S (Nasdaq: GMAB) reported topline results from the Phase III CANDOR study, sponsored by Amgen, of daratumumab in combination with carfilzomib and dexamethasone (Kd) versus Kd alone in patients with multiple myeloma who have relapsed after one to three prior therapies (Press release, Genmab, SEP 13, 2019, View Source [SID1234539492]). The study met the primary endpoint of improving progression free survival (PFS). The regimen resulted in a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with Kd (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS for patients treated with daratumumab in combination with Kd had not been reached by the cut-off date compared to a median PFS of 15.8 months for patients who received Kd alone.

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There was a higher frequency of adverse events reported with daratumumab plus Kd, a three-agent regimen, than with Kd, a two-agent regimen. The types of observed adverse events were consistent with the known safety profiles of the individual agents. The most frequently reported treatment-emergent adverse events (greater than or equal to 20%) in the daratumumab plus Kd arm were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea.

The CANDOR data will be submitted to a future medical meeting and Amgen will discuss the data with health authorities in preparation for regulatory submissions.

"We are very pleased that daratumumab has shown efficacy in yet another combination regimen – in this case with carfilzomib, a newer member of the proteasome inhibitor class. We look forward to the potential for this combination to provide an additional regimen for patients diagnosed with relapsed multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

About the CANDOR study
The Phase III trial (NCT03158688) is a randomized, open-label study that includes approximately 460 patients with multiple myeloma who have relapsed after 1 to 3 prior therapies. Patients were randomized to receive either daratumumab in combination with carfilzomib (a proteasome inhibitor) and dexamethasone (a corticosteroid) or carfilzomib and dexamethasone alone. In the daratumumab treatment arm, patients received 8 milligrams per kilogram (mg/kg) on days 1 and 2 of cycle 1, then 16 mg/kg once weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. In both treatment arms carfilzomib was dosed twice weekly (20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter) and dexamethasone was given weekly (40 mg orally or via IV infusion). 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 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 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.5

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.6 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 and 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. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. 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).6,7,8,9,10

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.

Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin showed non-inferiority when compared to intravenous formulations for people with HER2-positive breast cancer

On September 13, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the phase III FeDeriCa study met its primary endpoint (Press release, Hoffmann-La Roche, SEP 13, 2019, View Source [SID1234539487]). The study showed a new investigational fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab), administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy, demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) compared to standard IV infusion of Perjeta plus Herceptin and chemotherapy in people with HER2-positive early breast cancer (eBC). The safety profile of the FDC of Perjeta and Herceptin was consistent with that of Perjeta and Herceptin administered intravenously.1,2

"With this single injection under the skin, people with HER2-positive breast cancer receiving Perjeta and Herceptin can have a faster treatment option," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Our medicines have helped millions of people living with HER2-positive breast cancer and this latest development is particularly exciting as, for the first time, we have combined two therapeutic antibodies as a single subcutaneous formulation."

SC administration of the FDC takes approximately 8 minutes for the initial loading dose, and approximately 5 minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions for the combination.1,2,3

Full data from the FeDeriCa study will be submitted for presentation at an upcoming medical meeting and to health authorities around the world.

About the FeDeriCa study
FeDeriCa is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy in people with HER2-positive eBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings.4 The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumour tissue detectable at the time of surgery.4

About the FDC of Perjeta and Herceptin
The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.

Trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin and pertuzumab is the same monoclonal antibody as in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but to different places.5 The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.5

The standard IV formulation of Perjeta in combination with IV Herceptin and chemotherapy (the Perjeta-based regimen) is approved in over 100 countries for the treatment of both early and metastatic HER2-positive breast cancer. In the neoadjuvant eBC setting, the Perjeta-based regimen has been shown to almost double the rate of pCR compared to Herceptin and chemotherapy.6 Additionally, the combination has been shown to significantly reduce the risk of recurrence of invasive disease or death in the adjuvant eBC setting.7 In the metastatic setting, the combination has shown an unprecedented survival benefit in previously untreated (first-line) patients with HER2-positive metastatic breast cancer.8

Halozyme’s Enhanze drug delivery technology may enable and optimise SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.9

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and metastatic HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.10 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test which identifies people who will likely benefit from these medicines at the onset of their disease.

Positive Results Announced From Phase 3 Trial Evaluating Fixed-Dose Subcutaneous Combination Of Perjeta® And Herceptin® Using Halozyme’s Enhanze® Drug Delivery Technology

On September 13, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that the global phase III FeDeriCa study conducted by Genentech, a member of the Roche Group, met its primary endpoint (Press release, Halozyme, SEP 13, 2019, View Source [SID1234539472]). The FeDeriCa study investigated a fixed-dose combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) for subcutaneous administration using Halozyme’s ENHANZE drug delivery technology in combination with intravenous chemotherapy. The study results demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) compared to standard intravenous (IV) infusion of Perjeta plus Herceptin and chemotherapy in patients with HER2-positive early breast cancer.

"The results of the phase III FeDeriCa study represent an important development for our ENHANZE drug delivery technology," said Dr. Helen Torley, President and CEO. "This is the first study to combine two therapeutic antibodies as a single fixed-dose subcutaneous formulation utilizing our ENHANZE technology, thereby providing patients with HER2-positive breast cancer the possibility of a faster treatment option."

Subcutaneous administration of the fixed-dose combination of Perjeta and Herceptin is approximately 8 minutes for the initial loading dose and approximately 5 minutes for each subsequent maintenance dose. Intravenous administration is approximately 150 minutes for the loading dose of Perjeta and Herceptin using standard IV formulations and between 60-150 minutes for subsequent maintenance infusions for the combination.

The study also demonstrated that the safety profile of the fixed dose subcutaneous combination of Perjeta and Herceptin was consistent with the safety profile of Perjeta and Herceptin administered intravenously.

Full data from the FeDeriCa study will be submitted for presentation at an upcoming medical meeting and to health authorities worldwide, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).1 2

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

Cotinga Pharmaceuticals Reports Fiscal 2019 Fourth Quarter and Full Year Financial and Operating Results

On April 5, 2019 Cotinga Pharmaceuticals Inc. (TSX Venture: COT; OTCQB: COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported its financial and operating results today for the three and nine months ended January 31, 2019 (Press release, Cotinga, SEP 12, 2019, View Source [SID1234550033]). Recent highlights include:

Advanced the clinical development of COTI-2:

Cotinga announced the initiation of dosing patients in the combination therapy trial at MD Anderson Cancer Center evaluating COTI-2 and cisplatin in a wide spectrum of cancers;
The Company announced that it has entered into a research partnership with St. Vincent’s University Hospital in Dublin, Ireland with the intent to evaluate COTI-2 in combination with eribulin in patients with triple negative metastatic breast cancer (TNBC).
"We were thrilled to announce this fiscal quarter the dosing of patients in our Phase 1b/2a trial at MD Anderson of COTI-2 plus cisplatin in patients with solid tumors, as well as announce our collaboration with St. Vincent’s Hospital to begin work in TNBC," said Alison Silva, President & Chief Executive Officer. "We look forward to continuing to provide updates at critical milestones as we advance COTI-2 through clinical development."

Upcoming Milestones

COTI-2:

Continue the dose escalation Phase 1b/2a combination therapy trial evaluating the effect of COTI-2 plus cisplatin in patients with solid tumors;
Contingent on the raising of necessary funds, initiate the TNBC trial with COTI-2 plus eribulin.
Corporate:

Strengthen the balance sheet;
Opportunistically pursue regional or co-development partnerships for COTI-2, pipeline programs and other technologies.
Financial Results

The Company’s operational activities during the quarter were primarily focused on advancing the Phase 1b/2a clinical trial of COTI-2.

For the three months ended January 31, 2019, the Company incurred a net loss of $0.280 million, or $0.01 per share, compared to a net loss of $1.278 million, or $0.08 per share, for the three months ended January 31, 2018. The decrease in net loss during the three-month period is primarily due to decreases in Research and Development (R&D) expense and General and Administrative (G&A) expense.

For the nine months ended January 31, 2019, the Company incurred a net loss of $1.756 million, or $0.08 per share, compared to a net loss of $3.301 million, or $0.21 per share, for the nine months ended January 31, 2018. The decrease in net loss during the period is primarily due to decreases in R&D, Sales and Marketing (S&M) expense and G&A expense, offset by changes in fair value warrant liability.

There was no revenue for the three and nine months ended January 31, 2019 or in the comparative periods in the prior year.

R&D expense in the three-month period ended January 31, 2019 decreased by $0.424 million over the same period in the prior year. The decrease in R&D expense in the three-month period is primarily due to a decrease in salaries and benefits due to lower headcount and preclinical testing as Cotinga continues to work to initiate an expanded protocol for its ongoing Phase 1b/2 clinical trial of COTI-2. For the nine months ended January 31, 2019, R&D expense decreased by $1.568 million over the same period in the year prior.

S&M expense in the three-month period ended January 31, 2019 decreased by $0.063 million over the same period in the year prior. The decrease in S&M expense in the three-month period is primarily due to rebranding undertaken during the three months ended January 31, 2018. For the nine months ended January 31, 2019, S&M expense decreased by $0.085 million over the same period in the prior year due to cost reductions implemented last financial year and rebranding undertaken during the Q3 2018.

G&A expense in the three-month period ended January 31, 2019 decreased by $0.496 million over the same period in the year prior. The decrease in G&A expense in the three-month period is primarily due to a decrease in salaries due to lower head count; streamlining of corporate operations and lower professional fees and share-based compensation. For the nine months ended January 31, 2019, G&A expense decreased by $1.174 million over the same period in the prior year.

Fair value of warrant liability for the nine months ended January 31, 2019, decreased by $1.389 million over the same period in the year prior.

Detailed operating and financial results can be found in the Company’s Unaudited Condensed Interim Financial Statements and Management Discussion and Analysis for the three and nine months ended January 31, 2019, which can be found on SEDAR at www.sedar.com or on the Company’s website at www.cotingapharma.com.

Innate Pharma reports first half 2019 financial results and business update

On September 12, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported its consolidated financial results for the first six months of 2019 (Press release, Innate Pharma, SEP 12, 2019, View Source [SID1234539489]). The financial statements are attached to this press release.

"As Innate Pharma celebrates our 20th anniversary this month, we are proud to acknowledge our employees, patients, physicians, and other stakeholders who support our ambition to develop new oncology therapies for patients with high unmet medical need. We continue to deepen and mature our proprietary and partnered pipeline of assets to strengthen our broad and balanced portfolio," commented Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "We are committed to continuing to invest and execute on our corporate, clinical and commercial strategy, which has recently been strengthened by the recruitment of new executive leadership. This will support our international expansion and execute on our long-term strategy to become a rare hemato-oncology focused commercial franchise."

Webcast and conference call will be held today at 2:00pm (CEST)

Dial in numbers:

France and International: +33 (0)1 76 70 07 94 US only: +1 631 510 7495

PIN code: 5173329#

The Interim financial report, the presentation and access to the live webcast will be available on Innate Pharma’s website 30 minutes ahead of the conference.

A replay will be available on Innate Pharma’s website after the conference call.

Financial highlights of the first half of 2019:

The key elements of Innate Pharma’s financial position and financial results as of and for the six-month period ended June 30, 2019 are as follows:

Cash, cash equivalents, short-term investments and financial assets amounting to €200.3m** as of June 30, 2019 (€202.7m as of December 31, 2018), including non-current financial instruments amounting to €35.3m (€35.2m as of December 31, 2018). This follows receipt in January of €108.8m as the second and final payment associated with the signature of the agreement signed with AstraZeneca in October 2018, as well as the payment of $50m (or €43.8m) to AstraZeneca in relation to Lumoxiti agreement and additional considerations relating to monalizumab and anti-CD39, paid to Novo Nordisk A/S and Orega Biotech, for $15m (or €13.1m) and €7.0m, respectively.
As of June 30, 2019, financial liabilities amounted to €5.0m compared to €4.5m as of December 31, 2018.
Revenue and other income of €59.2m for the six-month period ended June 30, 2019, as compared to €23.0m for the first half of 2018, restated, of which €51.6m result from revenue from collaboration and licensing agreements and €7.6m from research tax credit.

Revenue from collaboration and licensing agreements mainly result from to the spreading of the upfront payment from the agreements signed with AstraZeneca in April 2015 and October 2018, based on the completion of the work the Company is engaged to perform (€24.3m for monalizumab and €22.5m for IPH5201).
Operating expenses of €45.9m compared to €37.9m for the first half of 2018, restated, of which 80% are related to research and development (R&D).
R&D expenses increased by €4.3m to €36.6m for the six month period ended June 30, 2019, as compared to €32.3m for the first half of 2018. This increase mainly results from an increase of €4.2m in amortization of intangible assets.
General and administrative (G&A) expenses increased by €3.7m to €9.3m for the six-month period ended June 30, 2019 as compared to €5.6m for the first half of 2018. This increase mainly results from the increase in non-scientific advisory expenses relating to fees incurred in connection with a potential capital raising activity.
A net loss of €3.8m resulted from distribution agreement in the context of the the launch of Lumoxiti in the US performed by AstraZeneca.
Net income for the first half of 2019 was €13.2m compared to a net loss of €15.1m for the first half of 2018 restated.