On November 5, 2015 Rexahn Pharmaceuticals, Inc. (NYSE MKT: RNN), a clinical stage biopharmaceutical company developing next generation therapeutics for the treatment of cancer, reported that interim clinical data from an ongoing Phase IIa study of its novel anti-cancer drug candidate, Archexin, will be presented on Friday, November 6, 2015 at the 14th International Kidney Cancer Symposium in Miami, Florida (Filing, 8-K, Rexahn, NOV 5, 2015, View Source [SID:1234508020]).

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"We are excited to present interim data from the ongoing Phase IIa clinical trial showing that Archexin, in combination with everolimus (Afinitor), appears to be safe and well tolerated at the doses tested to date. We have also noted early evidence of clinical activity at low doses in patients with metastatic kidney cancer," commented Peter D. Suzdak, Chief Executive Officer. "We look forward to completing the randomized, open-label, 2-arm dose expansion study of Archexin in combination with everolimus versus everolimus alone in order to further evaluate Archexin in metastatic renal cell carcinoma."

Archexin Clinical Data

Interim data from the Phase IIa Archexin clinical trial will be presented on Friday, November 6, 2015 by study investigators, Drs. S. Tagawa, G. Chatta and N. Agarwal in a poster presentation entitled "RX-0201, An Anti-Sense Targeting AKT-1 to Treat Metastatic Renal Cancer – Preliminary Phase IIa Data."

The interim results show that at the dose levels tested to date, Archexin appeared to be safe and well tolerated. The most commonly reported adverse events in the patients taking both Archexin and everolimus included: thrombocytopenia, mouth ulcerations, decreased weight, facial edema, and hyponatremia. To date, none of these adverse events has been dose limiting.

Early evidence of the potential clinical activity of Archexin in combination with everolimus has been observed. Among the patients enrolled in the study, two patients experienced stable disease, which has persisted for 170 and 334 days (as of October 28, 2015). In addition, at the lowest dose tested one patient experienced a 15% reduction in tumor size, as compared to a baseline CT scan taken prior to treatment with Archexin and everolimus.

Scott Tagawa, MD, MS, Medical Director, Genitourinary Oncology Research Program, Associate Professor of Clinical Medicine and Urology, Division of Hematology & Medical Oncology, Weill Cornell Medical College, commented, "The treatment of patients with metastatic RCC remains a significant unmet medical need and the early evidence supporting the potential clinical benefit of Archexin is therefore very promising. With a unique mechanism of action targeting a well validated cancer pathway (Akt-1 suppression), it is possible that Archexin in combination with everolimus could have a two-fold effect in the treatment of RCC, both by inhibiting the growth and proliferation of RCC, but also potentially by overcoming resistance to mTOR inhibitors. I look forward to further evaluation of this promising approach."

The ongoing Phase IIa clinical study is designed to evaluate the efficacy of Archexin in combination with everolimus (Afinitor) to treat metastatic RCC patients and is being conducted in two stages. Stage 1 is an open-label, dose-escalation study designed to identify a safe and tolerable dose of Archexin when given in combination with everolimus. Stage 2 is a randomized, open-label, 2-arm dose expansion study of Archexin in combination with everolimus versus everolimus alone to determine safety and efficacy of the combination.

In Stage 1, escalating doses of Archexin of 125, 200 and 250 mg/m2/day are administered by continuous IV infusion for 14 days followed by 1 week of rest. Based on previous clinical data, the target dose of Archexin is anticipated to be no more than 250 mg/m2 per day. Patient assessments include safety, pharmacokinetics, laboratory and physical exams. Once the maximum tolerated dose of Archexin in combination with everolimus has been determined, thirty RCC patients will be randomized to receive either Archexin in combination with everolimus, or everolimus alone, in a ratio of 2:1.

The primary endpoint of Stage 2 is the percentage of progression free patients following eight cycles of therapy. Patients are scanned (CT or MRI) for the assessment of tumor progression after every 2 cycles of therapy. Secondary endpoints include pharmacokinetic profile, incidence of adverse events, changes in clinical laboratory tests and vital signs over time, tumor response, duration of response, time to response, and response rate. Exploratory endpoints include blood levels of AKT pathway biomarkers, tumor apoptosis biomarkers, or other relevant biomarkers.

In preclinical studies, Archexin has been shown to inhibit the growth of human renal cell carcinoma (RCC) cells in tissue culture. Archexin has also been shown to exhibit an additive anti-tumor effect when combined with other cancer drugs in inhibiting the growth of human RCC cells in tissue culture.

About Archexin

Archexin is a unique anti-sense drug candidate that specifically inhibits the cancer cell signaling protein Akt-1. Archexin is the only specific inhibitor of Akt-1 in clinical development. The activated form of Akt-1, which is involved in cancer cell growth, survival, angiogenesis, and drug resistance, has been shown to be present or elevated in more than 12 different human cancer cell lines, including pancreatic and renal cell carcinoma. By inhibiting Akt-1, Archexin has been shown to both inhibit the growth of renal cell carcinoma cell lines and exhibit a longer survival benefit in the human renal cell carcinoma animal xenograft model. Thus, while Akt-1 is a very specific anti-cancer target, it may have broad therapeutic potential across multiple types of cancer.

Archexin has completed a Phase I clinical trial in cancer patients with solid tumors and was shown to be safe and well tolerated. The dose-limiting toxicity was Grade 3 fatigue. In a small Phase IIa trial in advanced pancreatic cancer patients, Archexin in combination with gemcitabine was shown to be safe and well tolerated and showed a preliminary efficacy signal with a median survival of 9.1 months in evaluable patients.

Metastatic RCC represents an attractive market opportunity with an estimated annual incidence of 90,000 patients worldwide. Metastatic RCC patients receiving standard of care treatment have a poor prognosis with an overall survival of less than 2 years. Rexahn has received U.S. Food and Drug Administration (FDA) Orphan Drug Designation for Archexin for metastatic RCC as well as four other cancers.

On November 5, 2015 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol, reported its financial results for the quarter ended September 30, 2015 and provided a corporate update (Press release, Corcept Therapeutics, NOV 5, 2015, http://www.corcept.com/news_events/view/pr_1446758532 [SID:1234508043]).

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Corcept recorded net revenue of $13.3 million in the third quarter of 2015, compared to $7.3 million for the same period in 2014, an increase of 82 percent. The company reiterated its 2015 revenue guidance of $49 – $53 million.

Corcept reported a net loss on a GAAP basis of $0.6 million for the third quarter of 2015, compared to a GAAP net loss of $6.0 million for the same period in 2014. Excluding non-cash expenses, Corcept generated non-GAAP net income in the third quarter of $1.6 million, compared to a non-GAAP net loss of $3.9 million in the third quarter of 2014. A reconciliation of GAAP to non-GAAP net operating results is set forth below.

At September 30, 2015, Corcept held cash and cash equivalents of $36.5 million, compared to $37.0 million at the end of the prior quarter. This change in cash reflects the repayment of $1.8 million in principal due under the company’s capped royalty financing agreement (Royalty Financing). The company entered into the Royalty Financing in 2012 to fund the commercialization of Korlym and expects to make its final payment in 2017.

Based on its current plans, the company expects to reach cash flow breakeven, including payments of principal due under the Royalty Financing, without needing to raise additional funds.

"Our Cushing’s syndrome franchise continues to grow as more physicians appreciate that using Korlym to modulate the effect of excess cortisol can greatly improve their patients’ health," said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. "As we have said before, our efficient cost structure and the revenue growth in our Cushing’s syndrome business allows us to build our clinical infrastructure, further develop Korlym and advance our next-generation compounds."

Korlym for the Treatment of Triple-Negative Breast Cancer (TNBC)

In December 2015, at the San Antonio Breast Cancer Symposium, Corcept will present preliminary efficacy results of its Phase 1/2 open-label trial of Korlym in combination with eribulin (Halaven) to treat patients with metastatic TNBC.

CORT125134 Phase 2 Trials

CORT125134 is the lead compound in Corcept’s portfolio of proprietary next-generation cortisol modulators. It was well-tolerated in its Phase 1 trial and showed that it shares Korlym’s ability to potently modulate activity at the glucocorticoid receptor (GR), the essential quality in treating Cushing’s syndrome. In addition, when administered with a chemotherapeutic agent, CORT125134 slows tumor growth significantly in mouse models of TNBC and castration-resistant prostate cancer. In vitro, it similarly slows the growth of ovarian cancer tumor cells; in vivo testing in mouse models of ovarian cancer is in progress.

In the first quarter of 2016, the company plans to begin two Phase 2 clinical trials with CORT125134. One trial will be for the treatment of patients with Cushing’s syndrome. The other will administer CORT125134 with a companion chemotherapeutic or hormonal agent to treat patients with a solid tumor cancer.

"It’s an exciting time to join Corcept," said Robert S. Fishman, M.D., Corcept’s Chief Medical Officer. "We are exploring extending Korlym’s label to cover oncologic indications, our lead next-generation cortisol modulator, CORT125134, is about to enter multiple Phase 2 trials and we’re advancing additional selective cortisol modulating compounds toward the clinic."

Financial Discussion

Corcept recorded a GAAP net loss of $0.6 million in the third quarter of 2015, compared to $6.0 million in the third quarter of 2014, including non-cash stock-based compensation and accreted interest expense generated from the Royalty Financing of $2.2 million and $2.1 million in the third quarter of 2015 and 2014, respectively. Excluding these non-cash items, Corcept generated net income on a non-GAAP basis of $1.6 million in the third quarter of 2015, compared to a non-GAAP net loss of $3.9 million in the third quarter of 2014.

Operating expenses for the third quarter were $13.2 million, compared to $12.4 million for the third quarter of 2014. The increase was primarily due to increased staffing costs and additional spending on the Phase 1/2 trial of Korlym for the treatment of TNBC and the development of next-generation cortisol modulators.

In the third quarter of 2015, Corcept made a payment of $2.5 million under the Royalty Financing, of which $0.7 million represented accreted interest and $1.8 million reduced outstanding principal. In the same period of 2014, Corcept paid $1.3 million, of which $0.9 million represented accreted interest and $0.4 million reduced outstanding principal. Corcept expects to make its final payment under the Royalty Financing in 2017.

Corcept’s cash balance at September 30, 2015 was $36.5 million, compared to $37.0 million at June 30, 2015 and $24.2 million at December 31, 2014.

(Filing, 10-Q, Radius, NOV 5, 2015, View Source [SID:1234508058])

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On November 5, 2015 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) reported that new data from the ongoing dose-escalation and expansion studies of AG-221 and AG-120 in advanced hematologic malignancies will be presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, December 5-8, 2015 (Press release, Agios Pharmaceuticals, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107405 [SID:1234507986]).

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In total, five abstracts led by Agios describing new clinical data from the company’s cancer metabolism and rare genetic metabolic disorders programs have been accepted for presentation at ASH (Free ASH Whitepaper), as well as two abstracts detailing new findings from the Natural History Study of pyruvate kinase (PK) deficiency being conducted with Boston Children’s Hospital. Agios’ IDH inhibitors AG-221 and AG-120 are being developed in collaboration with Celgene.

The accepted abstracts are listed below and are now available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral Presentation

Date & Time: Sunday, December 6, 2015 at 5:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Advances in Targeted Therapy
Abstract Number: 323
Presentation Title: Safety and Efficacy of AG-221, a Potent Inhibitor of Mutant IDH2 That Promotes Differentiation of Myeloid Cells in Patients with Advanced Hematologic Malignancies: Results of a Phase 1/2 Trial
Location: Orange County Convention Center, W110

Poster Presentations

Date & Time: Saturday, December 5, 2015 from 5:30 p.m. to 7:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract Number: 1306
Presentation Title: Molecular Profiling and Relationship with Clinical Response in Patients with IDH1 Mutation-Positive Hematologic Malignancies Receiving AG-120, a First-in-Class Potent Inhibitor of Mutant IDH1, in Addition to Data from the Completed Dose Escalation Portion of the Phase 1 Study
Location: Orange County Convention Center, Hall A

Date & Time: Saturday, December 5, 2015 from 5:30 p.m. to 7:30 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract Number: 1310
Presentation Title: Longitudinal Pharmacokinetic/Pharmacodynamic Profile of AG-120, a Potent Inhibitor of the IDH1 Mutant Protein, in a Phase 1 Study of IDH1-Mutant Advanced Hematologic Malignancies
Location: Orange County Convention Center, Hall A

Date & Time: Sunday, December 6, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II
Abstract Number: 2509
Presentation Title: Evaluation of the Pharmacokinetics of AG-221, a Potent Mutant IDH2 Inhibitor, in Patients with IDH2-Mutation Positive Advanced Hematologic Malignancies in a Phase 1/2 Trial
Location: Orange County Convention Center, Hall A

Date & Time: Sunday, December 6, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II
Abstract number: 2136
Presentation Title: The Phenotypic Spectrum of Pyruvate Kinase Deficiency (PKD) from the PKD Natural History Study (NHS): Description of Four Severity Groups By Anemia Status
Location: Orange County Convention Center, Hall A

Date & Time: Monday, December 7, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract Number: 3337
Presentation Title: Molecular Characterization of 140 Patients in the Pyruvate Kinase Deficiency (PKD) Natural History Study (NHS): Report of 20 New Variants
Location: Orange County Convention Center, Hall A

Date & Time: Monday, December 7, 2015 from 6:00 p.m. to 8:00 p.m. ET
Session Title: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract Number: 3336
Presentation Title: Population Pharmacokinetics and Pharmacodynamics of AG-348 in Healthy Human Volunteers Guide Dose Selection for the Treatment of Pyruvate Kinase Deficiency
Location: Orange County Convention Center, Hall A

On November 5, 2015 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies, reported that data from its ongoing clinical studies of LentiGlobin BB305 in beta-thalassemia major and severe sickle cell disease (SCD) will be highlighted in oral and poster presentations at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Filing, 8-K, bluebird bio, NOV 5, 2015, View Source [SID:1234508002]). The company will also present preclinical data from its lead oncology program, bb2121, in three posters at ASH (Free ASH Whitepaper). bluebird bio is developing bb2121 as an anti-BCMA oncology therapy in collaboration with Celgene Corporation. Preliminary data from all six of these abstracts will become available on the ASH (Free ASH Whitepaper) conference web site at 9:00 a.m. ET today.

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"Our expanding clinical experience with LentiGlobin continues to show promising clinical benefit in patients with beta-thalassemia major and severe sickle cell disease," said David Davidson, M.D., chief medical officer, bluebird bio. "We are pleased to see a median HbAT87Q level of 5.2 g/dL in the seven Northstar patients with beta-thalassemia major of all genotypes followed for six months or more, as this represents a substantial proportion of their total hemoglobin. It is exciting that transfusion independence has been achieved in all of our patients with beta‑thalassemia major with non-β0/β0 genotypes followed for at least six months in Northstar and HGB-205. Varying degrees of transfusion reduction have been observed in patients with β0/β0 genotypes. As would be expected, longer follow-up is required to assess the extent of HbAT87Q production and the impact on transfusion requirements in these patients with β0/β0 genotypes since they produce no functional beta-globin at baseline. Turning to sickle cell disease, our first treated patient is producing increased levels of HbAT87Q since we last reported on this study in June. HbAT87Q represented 48 percent of total hemoglobin at nine months post-infusion, and the patient remains transfusion independent without sickle cell-related adverse events as of the data cut-off. These results support the transformative potential of gene therapy, and we look forward to sharing more data at ASH (Free ASH Whitepaper)."

"The three accepted oncology abstracts represent the great progress we have made building our immuno-oncology business," said Rob Ross, M.D., head of oncology, bluebird bio. "These posters describe the encouraging pre-clinical data supporting the development of bb2121 in multiple myeloma, including our robust manufacturing platform, and key scientific insights into engineering more potent CARs that are applicable across our planned oncology portfolio."

LentiGlobin Presentations

Update of Results from the Northstar Study (HGB-204): A Phase 1/2 Study of Gene Therapy for Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (LentiGlobin BB305 Drug Product) (Abstract #201)

Presenter: Mark C. Walters, M.D., UCSF Benioff Children’s Hospital, Oakland, CA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-off:

· Seven subjects have been monitored for at least six months post-infusion: three of the β0/β0 genotype and four of the non-β0/β0 genotype.

· The median level of HbAT87Q expression among these seven subjects is 5.2 g/dL (range 1.9 to 8.2 g/dL), with total hemoglobin ranging from 8.5 to 11.1 g/dL at last visit.

· All four non-β0/β0 subjects have been transfusion-free for at least 90 days, with a median of 287 days transfusion-free (range: 171 to 396 days).

· Two of the β0/β0 subjects have received a single transfusion post-discharge, and one remains transfusion-dependent.

· All subjects engrafted.

· The safety profile was consistent with autologous transplantation. No Grade 3 or higher drug-product related adverse events have been observed, and there is no evidence of clonal dominance after a median follow-up of 198 days (range: 65 to 492 days).

Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector (Abstract #202)

Presenter: Marina Cavazzana, M.D., Ph.D., Hôpital Universitaire Necker – Enfants Malades, Paris, France

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· The subject with severe SCD is producing approximately 51.5% anti-sickling hemoglobin (48 percent HbAT87Q, 1.8 percent HbF, 1.7 percent HbA2) at nine months post-infusion.

· The subject with severe SCD remains free of transfusions.

· The subject with severe SCD has not had a post-treatment hospitalization for a disease-related event despite ceasing chronic transfusions on Day +88.

· Both subjects with beta-thalassemia major have remained transfusion-free for at least 15 months post‑infusion, with consistent expression of HbAT87Q – both subjects are β0/βE genotype.

· One additional subject with beta-thalassemia major had one month follow-up post-infusion.

· No subject has experienced a drug product-related adverse event, and there is no evidence of clonal dominance.

Initial Results from Study HGB-206: A Phase 1 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease (Abstract #3233)

Presenter: John F. Tisdale, M.D., National Institutes of Health, Bethesda, MD

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· LentiGlobin BB305 drug product has been manufactured for 2 subjects with severe SCD and 1 subject has been infused.

· The safety profile has been consistent with autologous transplantation, with no Grade 3 or higher drug product-related adverse events.

bb2121 Presentations

Manufacturing an Enhanced CAR T Cell Product by Inhibition of the PI3K/Akt Pathway During T Cell Expansion Results in Improved In Vivo Efficacy of Anti-BCMA CAR T Cells (Abstract #1893)

Presenter: Molly Perkins, D.Phil., bluebird bio, Cambridge, MA

Date: Saturday, December 5, 2015

Abstract Results, as of July 31st Data Cut-Off:

· In an in vivo aggressive lymphoma model, mice treated with anti-BCMA CAR T cells cultured with IL-2 and an inhibitor of PI3K experienced complete and long-term tumor regression; mice treated with anti-BCMA CAR T cells cultured only with IL-2 experienced no effect on tumor growth and succumbed to the tumors within two weeks after treatment; anti-BCMA CAR T cells grown in IL-7 and IL-15 also did not affect tumor growth.

· In an in vivo multiple myeloma model, mice received a single administration of anti-BCMA CAR T cells cultured under various conditions; all treatment groups demonstrated tumor regression regardless of culture conditions. In a model of tumor relapse, two weeks after tumor clearance, surviving mice were re-challenged with the same multiple myeloma model on the opposite flank; only animals that had been treated with anti-BCMA CAR T cells cultured with the PI3K inhibitor were able to resist subsequent tumor challenge.

· These data suggest that inhibition of PI3K during ex vivo expansion may generate a superior anti-BCMA CAR T cell product for clinical use; this approach could potentially be used in manufacture of other anti-tumor CAR therapies.

A Novel and Highly Potent CAR T Cell Drug Product for Treatment of BCMA-Expressing Hematological Malignancies (Abstract #3094)

Presenter: Alena Chekmasova, Ph.D., bluebird bio, Cambridge, MA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· bluebird bio has developed a chimeric antigen receptor (CAR) targeting BCMA (bb2121) that consists of extracellular single chain variable fragment scFv antigen recognition domain derived from antibodies to BCMA linked to CD137 (4-1BB) co-stimulatory and CD3zeta chain signaling domains.

· Based on receptor density quantification bb2121 can recognize tumor cells expressing less than 800 BCMA molecules per cell.

· In a BCMA+ MM xenograph model, treatment with bb2121 resulted in rapid and sustained elimination of the tumors and 100 percent survival.

Characterization of Lentiviral Vector Derived Anti-BCMA CAR T Cells Reveals Key Parameters for Robust Manufacturing of Cell-Based Gene Therapies for Multiple Myeloma (Abstract #3243)

Presenter: Graham W.J. Lilley, M.Sc., bluebird bio, Cambridge, MA

Date: Sunday, December 6, 2015

Abstract Results, as of July 31st Data Cut-Off:

· Successful personalized medicine will require robust and reproducible cell manufacturing. A series of experiments were conducted to determine whether variations in anti-BCMA CAR surface expression resulted in changes in the activity of CAR T cells.

· The potency of the final drug product was shown to be independent of total anti-BCMA CAR expression on the cell surface.

· T cells transduced with varying MOIs to yield different amounts of CAR surface expression were diluted with donor-matched untransduced cells to achieve a uniform population of T cells containing 26 + 4 percent anti-BCMA CAR T cells. When exposed to tumor, these CAR T cell populations exhibited no difference in cytotoxicity against BCMA-expressing cells. All T cell productions easily achieved a level of anti-BCMA CAR expression that resulted in potent anti-BCMA activity.

· These data show that our manufacturing platform has been optimized to overcome significant challenges associated with personalized medicine by reducing the effects of variability while maintaining potency in autologous cellular drug product manufacturing.