On October 5, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has accepted for filing with Priority Review its New Drug Application (NDA) seeking accelerated approval for selinexor, its first in class, oral SINE compound, as a new treatment for patients with penta-refractory multiple myeloma (Press release, Karyopharm, OCT 5, 2018, View Source [SID1234529861]). The FDA also granted Karyopharm’s request for Priority Review and assigned an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA). In its acceptance letter, the FDA has stated that it is currently planning to hold an advisory committee meeting to discuss this application.

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"As a potential new therapy with a novel mechanism and compelling clinical profile, we believe oral selinexor, if approved, will provide a meaningful therapeutic option for patients battling highly resistant, penta-refractory myeloma," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "The acceptance of this NDA for review and grant of Priority Review mark significant milestones for the selinexor program, and further underscores the high level of unmet need in this patient population. We look forward to working with the FDA during the review process."

Provided marketing approval is granted by the FDA, Karyopharm plans to commercialize selinexor in the U.S. as early as the first half of 2019. The Company also plans to submit a Marketing Authorization Application to the European Medicines Agency in early 2019 with a request for conditional approval.

Priority Review is granted by the FDA to drugs that, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition when compared to standard applications. Selinexor has received both Orphan Drug and Fast Track designations from the FDA for the treatment for patients with penta-refractory multiple myeloma.

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,600 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like overall response rate (ORR). Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma, accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies. FDA’s Fast Track designation is available to therapeutics treating an unmet medical need in a serious condition; the Company has received Fast Track designation from the FDA specifically for the population treated in the STORM trial. In light of this recognition that the STORM patient population represents an unmet medical need and the positive top-line data reported in April and September 2018, the Company believes that the STORM study should support its request to the FDA for accelerated approval.

On October 5, 2018, Bellicum Pharmaceuticals, Inc. (the "Company") entered into an Open Market Sale AgreementSM (the "Sales Agreement") with Jefferies LLC, as sales agent ("Jefferies"), pursuant to which the Company may offer and sell, from time to time, through Jefferies, shares of the Company’s common stock having an aggregate offering price of up to $60.0 million (Filing, 8-K, Bellicum Pharmaceuticals, OCT 5, 2018, View Source [SID1234530607]). The shares will be offered and sold pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-226652).

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The Company is not obligated to sell any shares under the Sales Agreement. Subject to the terms and conditions of the Sales Agreement, Jefferies will use commercially reasonable efforts, consistent with its normal sales and trading practices, applicable state and federal law, rules and regulations and the rules of The Nasdaq Global Market, to sell shares from time to time based upon the Company’s instructions, including any price, time or size limits specified by the Company. Under the Sales Agreement, Jefferies may sell shares in privately negotiated transactions, as block transactions or by any other method or payment permitted by law deemed to be an "at-the-market" offering as defined in Rule 415 under the Securities Act of 1933, as amended. The Company will pay Jefferies a commission of up to 3.0% of the aggregate gross proceeds from each sale of shares, reimburse certain legal fees and disbursements and provide Jefferies with customary indemnification and contribution rights. The Sales Agreement may be terminated by Jefferies or the Company at any time upon notice to the other party.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K. The legal opinion of Cooley LLP relating to the shares of common stock being offered pursuant to the Sales Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy any shares under the Sales Agreement, nor shall there be any sale of such shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On October 5, 2018 Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX), an oncology company developing innovative medicines and imaging analysis technology for targeting and treating cancer, reported data from its OSPREY 2301 Study of PyLTM (18F-DCFPyL). PyL is the Company’s PSMA-targeted small molecule PET imaging agent designed to visualize prostate cancer (Press release, Progenics Pharmaceuticals, OCT 5, 2018, View Source [SID1234530641]). In the study, PyL demonstrated high sensitivity in reliably detecting distant metastatic prostate cancer lesions and high specificity in confirming the absence of pelvic lymph node disease. The associated strong positive predictive values (PPV) and negative predictive value (NPV) of PyL imaging in these disease settings indicate its potential high clinical utility.

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Dr. Michael Morris, Associate Professor at Memorial Sloan Kettering, and a lead investigator of the trial said, "These are highly encouraging results in a large, well-controlled and rigorous trial showing PyL has excellent positive and negative predictive value in assessing the distribution of disease in men with high-risk prostate cancer. Furthermore, in men intended to go to surgery, the specificity of PyL was exceedingly good. Taken together, a PyL PET avid lesion is a reliable reflection of histologically proven disease and may provide additional important information to men with prostate cancer and their doctors. That information may provide important guidance in the decision-making for their treatment."

Phase 2/3 Trial Results

The trial examined the diagnostic performance of PSMA-targeted PET imaging agent, PyL, to detect prostate cancer in pelvic lymph nodes in patients with high risk locally advanced prostate cancer (Cohort A) and distant metastases in patients with metastatic or recurrent (Cohort B) prostate cancer. The diagnostic performance of PyL PET imaging in this "gold standard" trial was evaluated against histopathology as the standard of truth. The OSPREY study dosed 385 patients with either high-risk locally advanced prostate cancer (268) or metastatic or recurrent prostate cancer (117). The study’s co-primary endpoints were the assessment of specificity and sensitivity of PyL PET imaging in Cohort A to detect prostate cancer in pelvic lymph nodes in patients scheduled to undergo radical prostatectomy with extended pelvic lymph node dissection. Key secondary endpoints for Cohort A were positive predictive value and negative predictive value. The study also evaluated several key secondary endpoints in Cohort B, including the sensitivity and positive predictive value of PyL PET imaging in detecting metastatic prostate cancer in patients where lesion biopsies (bone, soft tissues, lymph nodes other than pelvic lymph nodes) were feasible.

In the trial, the diagnostic performance of PyL in detecting disease in pelvic lymph nodes (Cohort A) showed a high specificity (96-99% among the three blinded independent readers), meeting the first co-primary endpoint of the trial, with the lower bound of the 95th percent confidence interval (94-96%) exceeding 80%. The sensitivity of 31-42%, did not meet the second co-primary endpoint, as the lower bound of the 95th percentile confidence interval (19-30%) did not exceed the required 40%. The positive predictive value and negative predictive value of pelvic lymph node detection were 78-91% and 81-84%, respectively.

In the metastatic or recurrent prostate cancer setting (Cohort B), PyL exhibited sensitivity of 93-99% and positive predictive value of 81-88% in detecting metastatic lesions. Specificity and negative predictive value were not endpoints specified in the protocol for Cohort B as all men in Cohort B were suspected to have disease.

PyL was very well tolerated. A total of 27 (7%) subjects experienced at least one treatment related adverse event. There were no serious adverse events related to study drug. The most frequent drug related events included dysgeusia (2.1%) and headache (2.1%).

"The data from this trial shows the strength of PyL in prostate cancer detection, and its potential to be highly valuable for disease and treatment monitoring," said Dr. Vivien Wong, Executive Vice President of Development at Progenics. "While specificity and sensitivity are often used to describe diagnostic performance, PPV and NPV are increasingly considered more relevant indicators of actual clinical utility. Following our discussions with FDA, our Phase 3 trial design will use a primary endpoint based on PPV parameters in the biochemical recurrence setting."

"PyL imaging holds great promise in transforming how physicians manage and treat high risk, metastatic, and recurrent prostate cancer," said Mark Baker, Chief Executive Officer of Progenics. "Our data from OSPREY provides strong rationale for continued development, and we look forward to launching our Phase 3 trial by year-end."

Progenics plans to submit the full results from the trial for presentation at a medical meeting.

Progenics Reports Results of Phase 2/3 Trial of PSMA PET Imaging Agent PyL Page 3

About PyL for PET Imaging of Prostate Cancer

PyL (also known as [18F]DCFPyL) is a fluorinated PSMA-targeted Positron Emission Topography ("PET") imaging agent that enables visualization of both bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.

Investor Conference Call

Progenics will host a conference call today at 8:30 AM Eastern Time to discuss the approval. The live and replayed webcast of the call will be available through the Company’s website at www.progenics.com. To participate in the live call by phone, dial (877) 250-8889 (USA) or (720) 545-0001 (international) and enter the passcode 4282148. The replay of the call will be available for 90 days.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 161,360 new cases of prostate cancer will be diagnosed and about 26,730 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors.

On October 5, 2018 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that it will release its third quarter 2018 financial results on Thursday, November 1, 2018 at 7:00 a.m. ET (Press release, Teva, OCT 5, 2018, View Source;p=RssLanding&cat=news&id=2370421 [SID1234529812]).

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Teva will host a conference call and live webcast on the same day, at 8:00 a.m. ET to discuss its third quarter 2018 results and overall business environment. A Question & Answer session will follow this discussion.

In order to participate, please dial the following numbers (at least 10 minutes before the scheduled start time):

United States 1 (866) 966-1396
International +44 (0) 2071 928000
For a list of other international toll-free numbers, click here.
Passcode: 7193665
A live webcast of the call will also be available on Teva’s website at: ir.tevapharm.com Please log in at least 10 minutes prior to the conference call in order to download the applicable software.

Following the conclusion of the call, a replay of the webcast will be available within 24 hours on the Company’s website. The replay can also be accessed until November 30, 2018, 9:00 a.m. ET by calling United States 1 (866) 331-1332 or International +44 (0) 3333-009785; passcode: 7193665.

On October 5, 2018 The U.S. Food and Drug Administration reported a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years (Press release, US FDA, OCT 5, 2018, View Source,aged%2027%20through%2045%20years. [SID1234607430]). Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

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"Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. "The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing."

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.