On October 6, 2018 Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, reported updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Loxo Oncology, OCT 6, 2018, View Source [SID1234529804]). In these 38 patients, approximately 3.5 months of additional patient follow-up were available, as were first follow-up scans for the nine patients most recently enrolled. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy, with median follow-up of 8.4 months. Seven of seven (100%) responding RET fusion-positive thyroid cancer patients remained on therapy, with median follow-up of 8.5 months. Inclusion of new restaging data for the most recently enrolled patients resulted in a 59% overall response rate (56% confirmed overall response rate) in the presented subset of RET-mutant MTC patients, and a 78% confirmed overall response rate in the presented subset of RET fusion-positive thyroid cancer patients. These data are being presented today at the 88th Annual Meeting of the American Thyroid Association.

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"I am very pleased to present the latest LOXO-292 clinical data to colleagues at ATA, demonstrating the activity and safety profile of this promising new agent for RET-altered thyroid cancers," said Lori J. Wirth, M.D., associate professor of medicine at Harvard Medical School and Massachusetts General Hospital. "In the months since ASCO (Free ASCO Whitepaper) we continue to see encouraging early evidence that LOXO-292 has the potential to provide durable responses in heavily pre-treated patients with RET-driven cancers, with a promising safety profile at the Phase 2 dose of 160 mg BID. RET has been a known oncogene in thyroid cancer for many years and I am hopeful that these LOXO-292 data can further increase the awareness of this important target and, with Breakthrough Therapy Designation in hand, that the clinical program will quickly advance to reach our patients in need. "

Trial Background

LIBRETTO-001 is a Phase 1/2 trial of LOXO-292 in advanced cancer patients who primarily have activating RET alterations. LIBRETTO-001 contains a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The primary endpoint of the Phase 1 is the determination of the maximum tolerated dose (MTD) or recommended dose for further study. Secondary endpoints include safety, overall response rate (by RECIST 1.1) and duration of response. Initial clinical data were first reported at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Key Data Presented

The data presented today were based on a July 19, 2018 data cut-off date and included the 29 patients with RET-mutant MTC and the nine patients with RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting.

Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Of the patients with RET-mutant MTC, 79% had previously received cabozantinib or vandetanib and 45% had received prior treatment with both agents. Of the patients with RET fusion-positive thyroid cancer, 78% had previously received radioactive iodine and 78% had previously received sorafenib or lenvatinib.

With 3.5 months of additional follow-up since the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy and in response (median follow-up of 7.6 months for all 29 patients; median follow-up of 8.4 months for responding patients). Seven of seven (100%) responding RET fusion-positive thyroid remained on therapy and in response (median follow-up of 7.6 months for all nine patients; median follow-up of 8.5 months for responding patients). The longest treated patient was the first RET-mutant MTC patient enrolled, who had been on therapy for more than 13 months as of the data cut-off date.

The new data cutoff date allowed for the inclusion of first follow-up scans for nine patients (seven with RET-mutant MTC and two with RET fusion-positive thyroid cancer) who had not had any post-baseline response assessment as of the ASCO (Free ASCO Whitepaper) presentation. Of 29 patients with RET-mutant MTC, 17 demonstrated an objective response by RECIST 1.1 (two complete responses and 15 partial responses, including two patients with unconfirmed partial responses awaiting confirmatory response assessments) and seven additional patients demonstrated evidence of tumor regression (-12% to -26%). The overall response rate was 59% (17/29) (95% CI: 39%-77%) and the confirmed overall response rate was 56% (15/27) (95% CI: 35%-75%). Included in this analysis are two patients with non-measurable disease at baseline (1 confirmed complete response, 1 stable disease). Of nine patients with RET fusion-positive thyroid cancer, seven demonstrated an objective response by RECIST 1.1 (all partial responses) and one additional patient demonstrated evidence of tumor regression (-21%). The confirmed overall response rate was 78% (7/9) (95% CI: 40%-97%). Included in the analysis is one patient with non-measurable disease at baseline (stable disease). Response assessments were performed by the local clinical trial sites.

Anti-tumor activity was observed regardless of RET mutation, RET fusion partner, and prior multikinase inhibitor treatment. One patient, with RET fusion-positive thyroid cancer, had RECIST target lesions in the central nervous system (CNS) and exhibited an intracranial partial response by RECIST 1.1, pending confirmation.

Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were diarrhea (15% Grade 1, 7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0% ≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17% Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1% Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade 3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade 3): tumor lysis syndrome, increased ALT/AST, diarrhea, and thrombocytopenia. All resolved with dose interruption. 160mg BID has been advanced as the Phase 2 dose, with dose exploration at 200mg BID ongoing to further characterize LOXO-292 safety and efficacy.

The presentation will be available online at View Source

About LOXO-292
LOXO-292 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 has been granted Breakthrough Therapy Designation by the U.S. FDA.

LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial. For additional information about the LOXO-292 clinical trial, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient RET Clinical Trial Hotline at 1-855-RET-4-292 or email [email protected].

About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary and other thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC). Both RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET.

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.