On October 27, 2015 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD), a leading immuno-oncology company, reported that it is pleased to announce its first regulatory approval facilitating commencement of the landmark Phase IIb clinical study of IMP321, Prima’s lead compound (Filing, 6-K, Prima Biomed, OCT 27, 2015, View Source [SID:1234507819]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The AIPAC (Active Immunotherapy PAClitaxel) clinical trial application has been cleared by Belgium’s Federal Agency for Medicines and Health Products (FAMHP). AIPAC is a multi-national, randomized, double-blind, placebo-controlled Phase IIb study of IMP321 in metastatic breast cancer which has received Scientific Advice from the European Medicines Agency (EMA). Prima continues work to obtain ethics approval by the Institutional Review Boards (IRB) at the chosen study sites in Belgium. IRB approval is the final approval required before trial initiation.

Prima’s CSO & CMO, Dr. Frédéric Triebel said, ‘Prima BioMed has, over the last 10 months, assembled a first class team to work on AIPAC. The clearing of our study protocol by FAMHP represents a big step forward for the team and we are on track to commence the study by the end of 2015.’

AIPAC – A key study
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

IMP321 has been shown in an open-label Phase I study1 to be able to double the expected six-month response rate in HER-2 negative metastatic breast cancer patients receiving standard-of-care paclitaxel, from a 25% historic response rate2 (RECIST criteria) to 50% when combined with IMP321. AIPAC has been designed to confirm this expected response and evaluate its effect on patient survival in a randomized, double blind, placebo-controlled setting and in a comparable patient population. Progression-Free Survival (PFS) will be AIPAC’s primary endpoint. RECIST response rates and Overall Survival are among the secondary endpoints. The design of the study has been examined by the EMA’s Scientific Advice expert panel in the view of using these data for Marketing Authorization in the EU in tested setting.

The protocol that arose from Prima’s interaction with the EMA will see women recruited into AIPAC with metastatic breast cancer where the tumour is HER-2-negative but hormone receptor positive. These patients will be receiving paclitaxel as first line chemotherapy after having failed on hormone therapy. They will represent a large patient population (hormone receptor-positive breast cancer is accounting for app. 75 percent of all cases) for which there are few viable treatment options, as indicated by the fact that PFS in such patients can be as low as six months3.

In the AIPAC study, patients will be administered subcutaneous doses of IMP321 on days 2 and 16 of a weekly regimen of paclitaxel, the day after their paclitaxel infusion.

AIPAC will aim to initially recruit 15 patients for a smaller safety run-in in three different countries. This section of the trial will test in combination with paclitaxel the safety of IMP321 in doses up to 30 mg per dose, which has previously been shown to be safe when tested as a monotherapy4 and is significantly higher than the maximum 6.25 mg dose from the Phase I in metastatic breast cancer. This section of AIPAC, extending into 2016, and will yield valuable safety, pharmacokinetic and pharmacodynamic data that Prima expects to report in second half of 2016.

After the safety run-in the AIPAC investigators will proceed to recruit 196 patients, randomising them 1:1 to either standard-of-care paclitaxel plus placebo or paclitaxel plus IMP321 for six months as per the Phase I dosing regimen, after which the responding or stable patients will be maintained for another year with monthly IMP321 injections. The study has been powered to show a four-month PFS advantage for the treatment group. Allowing time for patient recruitment and follow-up, AIPAC’s expected duration is around three years. Throughout the study, an independent data monitoring committee will review patient safety, survival rates and demographics at regular intervals. No interim statistical analysis is planned.

Prima envisages setting up at least 30 study sites for AIPAC in six European countries – starting with Belgium, France and the Netherlands. While Belgian regulatory approval has now been received for AIPAC, the relevant approvals are still to be obtained for the other countries.

On October 27, 2015 United Therapeutics Corporation (NASDAQ: UTHR) reported its financial results for the third quarter ended September 30, 2015 (Press release, United Therapeutics, OCT 27, 2015, View Source [SID:1234507917]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased with our third quarter 2015 results as total revenues reached $386 million and each of our pulmonary arterial hypertension products realized their highest revenue levels ever," said Roger Jeffs, Ph.D., United Therapeutics’ President and Co-Chief Executive Officer. "We are also happy to report the first commercial sales of Unituxin for the treatment of high-risk neuroblastoma. These strong financial results will enable us to continue advancing our innovative product pipeline and returning value to our shareholders through our recently announced $500 million share repurchase program."

Financial Results for the Three Months Ended September 30, 2015

Revenues

Revenues for the three months ended September 30, 2015 increased by $56.3 million, compared to the three months ended September 30, 2014. The growth in revenues primarily resulted from: (1) a $22.6 million increase in Adcirca revenues, driven by price increases, which are determined by Eli Lilly and Company, and by an increase in the number of Adcirca bottles sold; and (2) a $19.9 million increase in Orenitram revenues due to an increase in the number of patients being treated. In addition, $4.7 million of the increase in revenue was due to our first commercial sales of Unituxin, which commenced during the three months ended September 30, 2015.

Expenses

Research and development expense.

Share-based compensation. The decrease in share-based compensation of $113.6 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, compared to a 45 percent increase during the same quarter in 2014.

General and administrative. The decrease in general and administrative expense of $12.8 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, resulted from a $13.0 million decrease in grants to non-profit organizations that provide financial assistance to patients with pulmonary arterial hypertension.

Share-based compensation. The decrease in share-based compensation of $208.8 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, as compared to a 45 percent increase during the same quarter in 2014.

Cost of product sales. The decrease in cost of product sales for the three months ended September 30, 2015, compared to the three months ended September 30, 2014, was due to the expiration of our royalty obligation to GlaxoSmithKline plc in October 2014. During the three months ended September 30, 2014, we incurred $24.9 million in royalty expense related to this royalty obligation.

Share-based compensation. The decrease in share-based compensation of $16.9 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, as compared to a 45 percent increase during the same quarter in 2014.

Gain on Sale of Intangible Asset

In September 2015, we sold the Rare Pediatric Priority Review Voucher (PPRV) we received from the FDA in connection with the approval of our Biologics License Application for Unituxin. In exchange for the voucher, we received $350.0 million from AbbVie Ireland Unlimited Company (AbbVie), a wholly-owned subsidiary of AbbVie Inc. The proceeds from the sale of the PPRV were recognized as a gain on the sale of an intangible asset, as the PPRV did not have a carrying value on our consolidated balance sheet at the time of sale.

Income Tax Expense

The provision for income tax expense is based on an estimated annual effective tax rate that is subject to adjustment in subsequent quarterly periods if components used to estimate the annual effective tax rate are updated or revised. Our estimated annual effective tax rates were approximately 38 percent and approximately 36 percent as of September 30, 2015 and September 30, 2014, respectively. Our 2015 estimated annual effective tax rate increased as of September 30, 2015 primarily due to a decrease in the estimated general business credits as compared to the prior year.

Non-GAAP Earnings

Non-GAAP earnings is defined as net income, adjusted for the following charges, which are presented net of our annual effective income tax rate, as applicable: (1) interest expense; (2) license fees; (3) depreciation and amortization; (4) impairment charges; and (5) share-based compensation expense (stock option, share tracking award and employee stock purchase plan). For 2015, we also adjusted non-GAAP earnings to eliminate the gain (net of our annual effective income tax rate) resulting from the sale of the PPRV in September 2015.

On October 27, 2015 Agenus Inc. (NASDAQ:AGEN), an immunology company discovering and developing innovative treatments for cancers and other diseases, reported its financial results for the third quarter ended September 30, 2015 (Press release, Agenus, OCT 27, 2015, View Source [SID:1234507795]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are rapidly advancing our broad pipeline of potentially best-in-class therapies and combination therapies for patients with cancer. We look forward to providing further details on this progress during our Analyst Day, scheduled for November 19 in New York City," said Dr. Garo H. Armen, Chairman and CEO of Agenus. "We have also strengthened our balance sheet by monetizing a portion of our QS-21 adjuvant royalty stream, which provided us with net proceeds of approximately $78 million. We also acquired the rights to antibodies targeting CEACAM1, expanding our portfolio to include powerful immune-modulators that may be complementary with other checkpoint modulators, including those in our pipeline."

Third Quarter 2015 Financial Results

For the third quarter ended September 30, 2015, Agenus reported a net loss attributable to common stockholders of $13.2 million, or $0.16 per share, basic and diluted, compared with a net loss attributable to common stockholders for the third quarter of 2014 of $8.2 million, or $0.13 per share, basic and diluted.

For the nine months ended September 30, 2015, the company reported a net loss attributable to common stockholders of $72.4 million, or $0.95 per share, basic and diluted, compared with a net loss attributable to common stockholders of $16.7 million, $0.28 per share, basic and diluted, for the nine months ended September 30, 2014.

The increase in net loss attributable to common stockholders for the nine-months ended September 30, 2015, compared to the net loss attributable to common stockholders for the same period in 2014, was primarily due to the advancement of our check point modulator programs including the $13.2 million charge for the acquisition of the SECANT yeast display platform in addition to other license and technology transfer arrangements. We also recorded a total of $14.2 million in non-cash expense for fair value adjustments to our contingent obligations. During the same period in 2014, the company recorded non-cash non-operating income of $10.7 million related to the fair value adjustment of our contingent obligations.

Cash, cash equivalents and short-term investments were $199.1 million as of September 30, 2015.

Third Quarter 2015 and Recent Corporate Highlights

In September, Agenus completed a $115 million non-dilutive royalty transaction pursuant to a Note Purchase Agreement with an investor group led by Oberland Capital Management, LLC for rights to a portion of the worldwide royalties on future sales of GlaxoSmithKline’s shingles (HZ/su) and malaria (RTS,S) prophylactic vaccine products that contain Agenus’ QS-21 adjuvant. The transaction resulted in net proceeds of approximately $78 million at closing.
Also in September, Agenus presented data at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) from an exploratory study showing the role of unique tumor neo-epitopes and immunological responses to Prophage in glioblastoma patients, highlighting the importance of patient-specific neo-epitopes in individualized immunotherapy for treating cancer.
In July, Agenus acquired rights to antibodies targeting Carcinoembryonic Antigen Cell Adhesion Molecule 1 (CEACAM1), a glycoprotein expressed on T cell and NK cell lymphocytes from Diatheva s.r.l., an Italian biotech company controlled by SOL S.p.A. CEACAM1 is overexpressed in melanoma, bladder, lung, colon, pancreas, and gastric cancers, and appears to mediate innate and adaptive immune suppression allowing tumors to escape immune destruction. Antibodies to CEAMCAM1 should be effective in treating patients with many forms of cancer.

On October 27, 2015 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported two poster presentations at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) being held November 5-9 in Boston, Massachusetts (Press release, Sunesis, OCT 27, 2015, View Source;p=RssLanding&cat=news&id=2103102 [SID:1234507820]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The details for the poster presentations are as follows:

Date and Time: Sunday, November 8, 2015 from 12:30 p.m. to 3:30 p.m. Eastern Time
Poster Title: PDK1 inhibitors SNS-229 and SNS-510 cause pathway modulation, apoptosis and tumor regression in hematologic cancer models in addition to solid tumors
Abstract/Poster Number: C198
Session Title: Therapeutic Agents: Small Molecule Kinase Inhibitors
Session ID: Poster Session C
Location: Exhibit Hall C-D

The full abstract can be viewed here.

Date and Time: Sunday, November 8, 2015 from 12:30 p.m. to 3:30 p.m. Eastern Time
Poster Title: SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation
Abstract/Poster Number: C186
Session Title: Therapeutic Agents: Small Molecule Kinase Inhibitors
Session ID: Poster Session C
Location: Exhibit Hall C-D

On October 27, 2015 Mylan N.V. (Nasdaq: MYL) reported the U.S. launch of Levoleucovorin Calcium Injection 10 mg (base)/mL; 175 mg (base)/17.5 mL and 250 mg (base)/25 mL Single-use Vials, which is the generic version of Spectrum Pharmaceuticals’ Fusilev for Injection (Press release, Mylan, OCT 27, 2015, View Source [SID:1234507800]). Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated for rescue use after high-dose methotrexate therapy in osteosarcoma. Levoleucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Levoleucovorin Calcium Injection 10 mg (base)/mL; 175 mg (base)/17.5 mL and 250 mg (base)/25 mL Single-use Vials had U.S. sales of approximately $200 million for the 12 months ending June 30, 2015, according to IMS Health.

Currently, Mylan has 259 ANDAs pending FDA approval representing $98.5 billion in annual brand sales, according to IMS Health. Fifty of these pending ANDAs are potential first-to-file opportunities, representing $33.4 billion in annual brand sales, for the 12 months ending December 31, 2014, according to IMS Health.