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BIND Therapeutics Announces Agreement with Merck to Develop Targeted Accurin™ Nanomedicines for Oncology

On November 6, 2014 BIND Therapeutics reported a joint research and development agreement with Merck, known as MSD outside the United States and Canada, through a subsidiary, to discover and develop novel nanomedicines for oncology (Press release BIND Therapeutics, NOV 6, 2014, View Source [SID:1234500928]). This collaboration will leverage BIND’s proprietary nanomedicine technology to create targeted Accurins based on novel, potent payloads from Merck’s preclinical oncology portfolio.

The first two Merck compounds include a kinesin spindle protein (KSP) inhibitor and a polo-like kinase 1 (PLK1) inhibitor. Both KSP and PLK1 are regulators of cellular mitosis and are considered essential to the proliferation of cancer cells. These pathways have proven difficult to target effectively using conventional agents due to therapeutic index limitations.

“This is an exciting and unique collaboration for BIND as it provides us with novel proprietary payloads to develop as Accurin product candidates for our internal pipeline,” said Scott Minick, Chief Executive Officer of BIND Therapeutics. “The structure of this agreement marks an advancement in our collaboration approach and demonstrates the strength of our leadership position in the field of nanomedicine.”

“We are pleased to collaborate with BIND Therapeutics to expand Merck’s active oncology discovery programs,” said Dr. Eric Rubin, vice president, clinical oncology, Merck Research Laboratories. “Merck is focused on exploring immuno-oncology and other promising pathways, and we look forward to combining compounds from our oncology portfolio with BIND’s nanomedicine technology platform.”

Under the terms of the agreement, BIND will apply its Medicinal Nanoengineering platform to develop targeted Accurins based initially on Merck-supplied investigational KSP and PLK1 inhibitors. The agreement also includes the option to incorporate additional Merck compounds in the future. BIND will fund and conduct research and development activities to advance Accurin product candidates based on these agents through first-in-human clinical studies, after which Merck and BIND will alternate in choosing whether or not to further develop and commercialize the Accurin products. If BIND opts in, in most scenarios there will be no payments made to Merck beyond a royalty on future product sales. If Merck opts in, it will pay BIND a fee based on a multiple of BIND’s research and development expenses, plus a royalty on future product sales. Further terms of the agreement were not disclosed.

FDA Grants Orphan Drug Designation to Merrimack Pharmaceuticals’ MM-141 for the Treatment of Pancreatic Cancer

On November 5, 2014 Merrimack Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to their investigational drug candidate MM-141 for the treatment of pancreatic cancer (Press release Merrimack, NOV 5, 2014, View Source [SID:1234500923]). MM-141 is a tetravalent bispecific antibody designed to block tumor survival signals by targeting receptor complexes containing IGF-1R and ErbB3 (HER3). The IGF-1R and HER3 complexes both activate a major cellular signaling pathway that allows tumor cells to grow and develop resistance to therapies.

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"Receiving orphan drug designation for MM-141 is an important regulatory advancement in the development of our clinical program," said Ulrik Nielsen, Ph.D., Chief Scientific Officer and Co-Founder of Merrimack. "Pancreatic cancer is an aggressive and devastating disease, with a five year survival rate of 6% and a low early detection rate. Merrimack is dedicated to changing the landscape of this disease for patients across all lines of therapy. We look forward to advancing the clinical development of MM-141 as we believe that it has the potential to significantly inhibit tumor survival signaling and address pathways of therapeutic resistance in this indication."

The FDA’s Office of Orphan Products Development (OOPD) designates orphan status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States. This orphan drug designation will potentially provide Merrimack Pharmaceuticals with seven-year marketing exclusivity for MM-141 and other benefits if the drug is approved by the FDA.

MM-141 is Merrimack’s sixth oncology candidate to enter clinical development and is currently being tested in a Phase 1 dose-escalation clinical study. A Phase 2 study testing MM-141 in combination with nab-paclitaxel and gemcitabine in front line pancreatic cancer is expected to start in 2015.

Advaxis Submits Investigational New Drug Application for ADXS31-142 (ADXS-PSA) for the Treatment of Metastatic Castration Resistant Prostate Cancer

On November 5, 2014 Advaxis reported that the Company has submitted an Investigational New Drug application (IND) to the United States Food and Drug Administration (FDA) to conduct the first-in-human study of ADXS31-142 for the treatment of metastatic castration resistant prostate cancer (mCRPC) (Press release Advaxis, NOV 5, 2014, View Source [SID:1234500921]). ADXS31-142 is Advaxis’s lead Lm-LLO immunotherapy designed to specifically target prostate-specific antigen (PSA).

Pending FDA’s acceptance of the IND submission, the proposed Phase 1/2 protocol is designed to evaluate the safety and efficacy of ADXS31-142 as monotherapy and in combination with KEYTRUDA (pembrolizumab), the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States, by Merck, known as MSD outside the United States and Canada, through its subsidiaries.

The Phase 1 part of the trial is designed to identify a recommended dose for ADXS31-142 when used alone and when combined with KEYTRUDA. The Phase 2 part of the trial will assess the safety and efficacy of the combination regimen. Advaxis and Merck will collaboratively oversee the conduct of the study, which is planned to begin in early 2015. Results from the open-label study will be used to determine the future clinical development program for the combination.

Within 30 calendar days of the IND filing, FDA will notify Advaxis of any questions it has or protocol revisions it requests which may delay this timing. Advaxis plans to work with the FDA review team to address any questions or requests that arise within this 30-day window.

"With the filing of our ADXS31-142 IND, we are on track to begin a Phase 1/2 human clinical trial with a second Lm-LLO immunotherapy investigational new drug in early 2015," commented Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "This is another important milestone for Advaxis as we continue to advance our pipeline of immunotherapy candidates and investigate novel combinations with checkpoint inhibitors and other synergistic agents that we believe may offer new treatment options for patients with cancer."

Both ADXS31-142 and KEYTRUDA are members of a new class of cancer treatments known as immunotherapies, which are designed to enhance the body’s own defenses in fighting cancer. Data from preclinical studies suggest that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an enhanced anti-tumor immune response. The goal of the Phase 1/2 trial is to begin examining that potential.

Lilly’s CYRAMZA® (ramucirumab) in Combination with Paclitaxel Granted FDA Approval for Advanced Gastric Cancer After Prior Chemotherapy

On November 5, 2014 Eli Lilly and Company reported that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA (ramucirumab) in combination with paclitaxel (a type of chemotherapy) as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy (Press release, Eli Lilly, NOV 5, 2014, View Source [SID:1234500920]). CYRAMZA now has two FDA approvals for these patients. Today’s announcement follows the April approval of CYRAMZA as a single agent – the first approval of a treatment in the U.S. for patients in this setting.

“This FDA approval of CYRAMZA represents another milestone for people battling this devastating and difficult-to-treat disease,” said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. “Lilly is pleased to continue delivering on its commitment to provide new treatment options to people living with cancer and those who care for them.”

Stomach cancer is the fifth most common cancer in the world and is the third-leading cause of cancer death.i In the U.S., approximately 22,000 people will be diagnosed with stomach cancer in 2014.ii CYRAMZA (ramucirumab injection 10 mg/mL solution) is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or GEJ adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

This FDA approval for CYRAMZA is based on the Phase III RAINBOW trial, which compared CYRAMZA plus paclitaxel to placebo plus paclitaxel. Efficacy endpoints in the trial included the major efficacy outcome measure of overall survival and the supportive efficacy outcome measures of progression-free survival and objective response rate. The labeling for CYRAMZA contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. CYRAMZA should be permanently discontinued in patients who experience severe bleeding. See the Important Safety Information at the end of this press release and the Prescribing Information.

CYRAMZA has been granted Orphan Drug Designation by the FDA for this indication. Orphan drug status is given in the U.S. by the FDA’s Office of Orphan Products Development (OOPD) to medicines that show promise for the treatment of rare diseases.

Corcept Therapeutics Announces Third Quarter 2014 Financial Results and Provides Corporate Update

On November 4, 2014 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic, oncologic and psychiatric disorders reported its financial results for the quarter ended September 30, 2014 (Press release, Corcept Therapeutics, NOV 4, 2014, http://www.corcept.com/news_events/view/pr_1415137296 [SID:1234511994]). The company also provided an update on its clinical programs and revised its 2014 revenue guidance.

Third Quarter Financial Results and 2014 Revenue Guidance

Corcept recognized $7.3 million in net revenue for the third quarter of 2014 compared to $5.9 million in the second quarter, an increase of 24 percent. The company’s net loss in the third quarter on a GAAP basis was $6.0 million, or $0.06 per share, compared to a net loss of $7.6 million, or $0.07 per share, in the second quarter.
The company’s net loss on a GAAP basis included significant non-cash items of $2.1 million in the third quarter and $2.2 million in the second quarter. Excluding these items, the company’s net loss on a non-GAAP basis was $3.9 million, or $0.04 per share, for the third quarter of 2014 and $5.4 million or $0.05 per share, for the second quarter.
As of September 30, 2014, the company held cash and cash equivalents of $26.8 million.
The company revised the range of its 2014 revenue guidance to $25-27 million.
"Our Cushing’s syndrome commercial business continues to grow and now generates cash to fund an increasing portion of our research and development activities," said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. "While there is a group of endocrinologists who have seen Korlym’s benefits and have become repeat prescribers, there are many physicians who have not yet written their first prescription. These physicians represent the potential for better treatment for more patients and significant future revenues."

Clinical Pipeline Progress

"We expect to have identified tolerable doses of Korlym and Halaven (eribulin) in our triple-negative breast cancer study by year-end, when the study’s efficacy phase is scheduled to begin. In September, we began dosing patients in our Phase 1 trial of CORT 125134. We will advance additional selective 1 glucocorticoid receptor (GR) antagonists into the clinic next year. GR antagonism is an exciting area of research that will generate interesting data in 2015, both from our own studies and from those being undertaken by our academic collaborators."

Financial Results

For the third quarter of 2014, Corcept recognized net product revenue of $7.3 million. The company reported a net loss of $6.0 million, or $0.06 per share, for the third quarter of 2014 compared to a net loss of $10.9 million, or $0.11 per share, for the same period in 2013.

The net loss on a GAAP basis for the third quarter of 2014 and for the third quarter of 2013 included non-cash stock-based compensation expenses of $1.2 million and $1.3 million, respectively. The company also recognized non-cash interest expense related to its capped royalty financing transaction of $895,000 in the third quarter of 2014 and $1.1 million in the same period in 2013.

After adjusting for these items, the company’s net loss on a non-GAAP basis was $3.9 million, or $0.04 per share, for the third quarter of 2014, compared to $8.5 million, or $0.08 per share, for the third quarter of 2013. A reconciliation of GAAP net loss to non-GAAP net loss is included below.

Operating expenses were $12.4 million for the third quarter of 2014 and also for the corresponding period in 2013.

Selling, general and administrative expenses in the third quarter were $9.1 million compared to $7.2 million for the comparable period in 2013.
Research and development expenses in the third quarter of 2014 were $3.0 million, compared to $5.2 million for the third quarter of 2013.
Corcept’s cash balance as of September 30, 2014 was $26.8 million, compared to $54.9 million at December 31, 2013. Net cash used in the company’s operating activities for the third quarter of 2014 was $5.9 million as compared to $9.0 million for the second quarter of 2014 and $11.1 million for the first quarter of 2014.

About Korlym

Korlym competitively blocks the glucocorticoid receptor type II (GR), one of the two receptors to which cortisol normally binds, thereby inhibiting the effects of excess cortisol in patients with Cushing’s syndrome. In April 2012, Corcept made Korlym available as a once-daily oral treatment of hyperglycemia secondary to endogenous Cushing’s syndrome in adult patients with glucose intolerance or diabetes mellitus type 2 who have failed surgery or are not candidates for surgery. Korlym was the first FDA-approved treatment for that illness and the FDA has designated it as an Orphan Drug for that indication.

About Cushing’s Syndrome

Endogenous Cushing’s syndrome is caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing’s syndrome is an orphan indication that most commonly affects adults aged 20-50. An estimated 10-15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients annually in the United States. An estimated 20,000 patients in the United States have Cushing’s syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system in the body and can be lethal if not treated effectively.

About Triple-Negative Breast Cancer

Triple-negative breast cancer is a form of the disease in which the three receptors that fuel most breast cancer growth – estrogen, progesterone and the HER-2/neu gene – are not present. Because the tumor cells lack the necessary receptors, treatments that target estrogen, progesterone and HER-2 receptors are ineffective. In 2013, approximately 40,000 women were diagnosed with triple-negative breast cancer. There is no FDA-approved treatment and neither a targeted treatment nor an approved standard chemotherapy regimen for relapsed triple-negative breast cancer patients exists.

About CORT 125134

CORT 125134 is a potent, competitive antagonist at the GR-II receptor, but does not have affinity for the progesterone, estrogen, AR androgen or GR-I (mineralocorticoid) receptors. The company has begun a Phase 1 study of the safety and tolerability of CORT 125134, one of its next-generation selective GR-II antagonists.