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Jazz Pharmaceuticals to Present New Data at the Annual ASH Meeting

On November 7, 2016 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that eleven abstracts, including four oral presentations, supporting the company’s hematology and oncology portfolio will be presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, California, December 3-6, 2016 (Press release, Jazz Pharmaceuticals, NOV 7, 2016, View Source;p=RssLanding&cat=news&id=2220278 [SID1234516378]).

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"The data presentations at ASH (Free ASH Whitepaper) reflect our efforts in advancing our diversified pipeline of programs in hematology and oncology, including rare blood disorders such as acute lymphoblastic leukemia (ALL) and AML, and in complications of hematopoietic stem-cell transplantation (HSCT) such as hepatic VOD," said Karen Smith, M.D., Ph.D., global head of research and development and chief medical officer at Jazz Pharmaceuticals. "Of note, we look forward to sharing a post-hoc sub-analysis of Phase 3 survival data following allogeneic HSCT in older high-risk AML patients that compares CPX-351, also known as Vyxeos, with the standard of care."

The following oral and poster presentations focusing on Defitelio (defibrotide sodium) injection, Erwinaze (asparaginase Erwinia chrysanthemi) and CPX-351(cytarabine and daunorubicin liposome injection) will be presented at ASH (Free ASH Whitepaper).

Defitelio Related Oral and Poster Presentations

Presentation Title
Author
Presentation Number / Date / Time / Location
Timing of Initiation of Defibrotide Post-Diagnosis of Hepatic Veno-Occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome (SOS) Post-Hematopoietic Stem Cell Transplantation (HSCT): Exploratory Age-Group Analysis From an Expanded Access Study

Grupp S, et al.
Oral Presentation 66:
– December 3; 8:45 AM (PT); Manchester Grand Hyatt San Diego, Grand Hall B
– Session 721: Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Post-Transplant Complications
Impact on Outcomes of Baseline Bilirubin in Patients with Hepatic VOD/SOS Receiving Defibrotide Treatment: A Post-Hoc Analysis

Richardson P, et al.
Poster Presentation 2213:
– December 3; 5:30-7:30 PM (PT); San Diego Convention Center, Hall GH
– Session 721: Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster I
Treatment of Hepatic VOD/SOS Post-HSCT in Patients With Acute Leukemias: A Subgroup Analysis From the Defibrotide Expanded-Access Program
Richardson P, et al.
Poster Presentation 3412:
– December 4; 6:00-8:00 PM (PT); San Diego Convention Center, Hall GH
– Session 721: Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
VOD Related Abstract

Abstract Title
Author
Details
Stratification of Allogeneic HSCT Patients by Risk of Developing VOD: A Model for Assigning a Risk Score

Strouse C, et al.
Oral Presentation 983:
– December 5; 3:45 PM (PT); Manchester Grand Hyatt San Diego, Grand Hall B
Session 721: Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Post-Transplant Complications II
Diagnosis of VOD/SOS With or Without Multi-Organ Dysfunction (MOD) After HSCT: Analysis of a Multicenter Chart Review
Doede T, et al.
Online Only Publication;
Abstract 5756
Erwinaze Related Oral and Poster Presentations

Presentation Title
Author
Presentation Date / Time / Location
Population Pharmacokinetic Modeling of Intravenous Asparaginase Erwinia Chrysanthemi: Impact of Varied Infusion Rates on Exposure

Zomorodi K, et al.
Poster Presentation 1631:
– December 3; 5:30-7:30 PM (PT), San Diego Convention Center, Hall GH
– 614: Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster I
CPX-351 Related Oral and Poster Presentations

Presentation Title
Author
Presentation Date / Time / Location
Analysis of Efficacy by Age for Patients Aged 60–75 With Untreated Secondary Acute Myeloid Leukemia (AML) Treated With CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial
Medeiros B, et al.
Oral Presentation 902:
– December 5; 3:00 PM (PT); Marriot Marquis San Diego Marina, San Diego Ballroom AB
– Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Clinical Trials of Novel Drugs and Combinations in AML
Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated With CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial
Lancet J, et al.
Oral Presentation 906:
– December 5; 4:00 PM (PT); Marriot Marquis San Diego Marina, San Diego Ballroom AB
– Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Clinical Trials of Novel Drugs and Combinations in AML
Enhanced Cytarabine and Daunorubicin Population Pharmacokinetics When Administered as CPX-351: A Novel Liposomal Formulation Not Requiring Dose Reduction for Mild Renal or Hepatic Dysfunction

Nikanjam M, et al.
Poster Presentation 3955:
– December 5; 6:00 – 8:00 PM (PT); San Diego Convention Center, Hall GH
– Session 604: Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III

AML Related Poster

Presentation Title
Author
Presentation Number / Date / Time / Location
Burden of Acute Myeloid Leukemia (AML) Among Older Newly-Diagnosed Patients
Sacks N, et al.
Poster Presentation 4780:
– December 5; 6:00 – 8:00 PM (PT); San Diego Convention Center, Hall GH
– Session 904: Outcomes Research—Malignant Conditions: Poster III
Additionally, one Jazz-sponsored Investigator Initiated Research poster presentation focusing on CPX-351 as an investigational agent for the treatment of AML will be presented at ASH (Free ASH Whitepaper).

Presentation Title
Author
Presentation Number / Date / Time / Location
CPX-351 for the Treatment of High-Risk Patients (pts) With Acute Myeloid Leukemia (AML)
Assi, R, et al.

Poster Presentation 4047:
– December 5; 6:00 – 8:00 PM (PT); San Diego Convention Center, Hall GH
– Session 616: Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
Full details of the ASH (Free ASH Whitepaper) 2016 annual meeting can be found here (View Source) and abstracts can be found here (View Source).

About Defitelio1
In the U.S., Defitelio (defibrotide sodium) injection 80mg/mL received FDA marketing approval on March 30, 2016 for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication.

Defitelio is contraindicated in patients currently taking anticoagulants or fibrinolytics and in patients who are allergic to Defitelio or any of its ingredients. Defitelio may increase the risk of bleeding and should be withheld or stopped if significant bleeding occurs. Patients should be monitored for allergic reactions, especially if there is a history of previous exposure to Defitelio. The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.

Please see full Prescribing Information for Defitelio. (View Source)

In Europe, defibrotide is marketed under the name Defitelio▼(defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients undergoing HSCT therapy. It is the first and only approved treatment in Europe for severe VOD. In Europe, Defitelio is indicated in patients over one month of age. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy. ▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC. (View Source)

About VOD
HSCT is an aggressive, potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, and congenital immunodeficiency and autoimmune disorders.2 VOD is a rare complication of HSCT, which occurs in approximately 9-14% of HSCT patients.3,4 Hepatic VOD, also known as SOS, is an early and life-threatening complication affecting the sinusoidal endothelial cells of the liver, which can typically occur within the first 21 days following HSCT.4,5 Hepatic VOD progresses to multi-organ dysfunction in approximately 30-50% of cases.5 VOD with multi-organ dysfunction (MOD) is associated with an overall mortality (death) rate of 84%.3 MOD is characterized by the presence of renal or pulmonary dysfunction.6,7 VOD is often characterized by sudden weight gain, hepatomegaly (abnormally enlarged liver), and elevated bilirubin.6,7

About Erwinaze
Erwinaze (asparaginase Erwinia chrysanthemi) is currently approved in the U.S. for administration via intramuscular injection or via intravenous infusion in conjunction with chemotherapy. It is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.8 Erwinaze is derived from the bacterium Erwinia chrysanthemi and is therefore immunologically distinct from E. coli-derived asparaginase and suitable for patients with hypersensitivity to E. coli-derived treatments9. Outside of the U.S., Erwinaze is sold under the name Erwinase. Please consult local labeling for product information specific to your country.

Erwinaze is contraindicated in patients who have had serious allergic reactions to Erwinaze, or had serious swelling of the pancreas, serious blood clots, or serious bleeding with past L-asparaginase treatment. Erwinaze should be discontinued if any of the following occur: serious allergic reactions, including a feeling of tightness in the throat, unusual swelling/redness in the throat and/or tongue, or trouble bleeding; or severe inflammation of the pancreas. Glucose intolerance has been reported, which in some cases may be irreversible. If blood clots of bleeding occur, discontinue Erwinaze until symptoms resolve. The most common side effects of Erwinaze are allergic reactions, too much sugar in the blood, fever, swelling of the pancreas, local reactions (swelling, rash, etc. where the needle entered the skin), vomiting, nausea, blood clots, liver problems, stomach pain/discomfort, and diarrhea. Please see full Prescribing Information for Erwinaze. (View Source)

About Vyxeos (CPX-351)
CPX-351 (cytarabine and daunorubicin liposome injection) is an investigational product being evaluated for the treatment of AML and is a combination of cytarabine and daunorubicin encapsulated within a nano-scale liposome at a 5:1 molar ratio. The proposed trade name, Vyxeos, is conditionally approved by the FDA and is subject to confirmation upon approval of the NDA. CPX-351 was granted orphan drug status by the FDA and the European Commission for the treatment of acute myeloid leukemia. CPX-351 was granted Breakthrough Therapy Designation for the treatment of adults with therapy-related AML or AML with myelodysplasia-related changes and was also granted Fast Track designation by the FDA for the treatment of older patients with secondary AML. On October 3, 2016 Jazz announced the initiation of a rolling submission of a New Drug Application (NDA) to the FDA, seeking marketing approval of CPX-351 for the treatment of AML.

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a rapidly progressing and life-threatening blood cancer that rises in frequency with age.16 The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016.10 In the European Union, the number of new cases is estimated to be 20,100 in 2016.11

The median age at diagnosis is 67 and with rising age there is progressive worsening of prognosis.10,12 Advancing age is associated with increasing risk of specific chromosomal/mutational changes and risk of pre-malignant marrow disorders which give rise to more aggressive and less responsive forms of AML.13,14 As patients age there is also reduced tolerance for intensive chemotherapy.15 As a consequence, advances in supportive care, intensive chemotherapy, and bone marrow transplantation have primarily benefitted younger patients with approximately one third of patients 18-60 years of age achieving cure.13,15 Older patients have not achieved higher rates of cure or improved upon a 5-year survival rate of 10-20% in spite of 40 years of research.15,16

Cascadian Therapeutics Reports Third Quarter 2016 Financial Results and Provides Corporate Update

On November 7, 2016 Cascadian Therapeutics (NASDAQ: CASC), a clinical-stage biopharmaceutical company, reported third quarter highlights and reported financial results for the quarter ended September 30, 2016 (Press release, Cascadian Therapeutics, NOV 7, 2016, View Source [SID1234516374]).

"We continue to make strides on the clinical development front as we advance tucatinib in combination for patients with metastatic HER2+ breast cancer, including those with and without brain metastases," said Scott Myers, CEO of Cascadian Therapeutics. "There is significant need for improved therapies in this disease, and we continue to be impressed by the favorable safety profile observed in the tucatinib combination studies to date when compared with other HER2 therapies, as well as its potential to treat systemic disease and positively impact brain metastases."
Mr. Myers added, "We are looking forward to the presentation of updated clinical data from our ongoing Phase 1b ‘Triplet’ study of tucatinib plus capecitabine and trastuzumab at the San Antonio Breast Cancer Symposium in December, as well as updating everyone on our clinical and regulatory plans later this quarter."
THIRD QUARTER AND RECENT HIGHLIGHTS
Clinical Development

• HER2CLIMB, continues to be on track with enrollment of Phase 2 tucatinib (ONT-380) combination trial. This randomized, double-blind, placebo-controlled study is evaluating the safety and efficacy of tucatinib versus placebo in combination with capecitabine and trastuzumab in late stage HER2+ breast cancer patients, with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and T-DM1. Tucatinib, which has Fast Track designation from the FDA in this setting, is expected to enroll approximately 180 patients at sites in the U.S., Canada and select countries in Western Europe. Previously reported results from the ongoing Phase 1b study of the tucatinib "Triplet" combination demonstrated promising systemic activity, a favorable safety profile and activity against brain metastases, which represents a significant unmet medical need.

• Data presented at ESMO (Free ESMO Whitepaper) 2016 show early evidence of activity of tucatinib combination therapy in patients with cutaneous HER2+ metastases. In a poster presentation, Dr. Alison Conlin, study author and Medical Oncologist, Providence Cancer Center, Portland, OR, presented data on eight patients with
LOGO

HER2+ metastases to the skin who received the maximum tolerated tucatinib dose in combination with capecitabine and/or trastuzumab from the Company’s Phase 1b combination study. Patients had previously received a median of six lines of drug therapy. Responses observed in skin lesions in these patients included one complete response, four partial responses and three patients with stable disease, including one partial response of a patient receiving tucatinib and trastuzumab only.

• Continue to advance novel Chk1 cell cycle inhibitor with goal of conducting IND-enabling studies. Preclinical research has shown that select Cascadian Chk1 inhibitors display cellular potency in in vitro models against Chk1, are active against a diverse range of cancer cell lines, and demonstrate synergistic activity in combination with certain chemotherapeutic drugs.
Corporate Update

• Cascadian’s board of directors has called a Special Stockholder Meeting to vote on a reverse split of the Company’s common stock and a reduction of the authorized common stock. The objective is to make the stock accessible to a wider range of institutional investors, benefiting all stockholders, and ensure that the necessary financial structure is in place to execute product development and other necessary corporate initiatives. The stockholder vote on the proposal will be held on November 18, 2016. For details, see the proxy statement at www.sec.gov/edgar.

THIRD QUARTER 2016 FINANCIAL HIGHLIGHTS

• Cash, cash equivalents and investments totaled $71.6 million as of September 30, 2016, compared to $56.4 million at December 31, 2015, an increase of $15.2 million, or 27.0%. The increase was primarily the result of net proceeds of $43.3 million from the Company’s June 2016 financing offset by cash used to fund operations of $28.1 million.

•
Net loss attributable to common stockholders for the three months ended September 30, 2016 was $11.8 million, or $0.09 per basic and diluted share, compared with a net loss attributable to common stockholders of $4.6 million, or $0.05 per basic and diluted share, for the comparable period in 2015. The increase in net loss attributable to common stockholders for the quarter was primarily due to increases in research and development expenses of $2.2 million primarily due to greater activity related to the development of the Company’s product candidates and increases in general and administrative expenses of $1.4 million primarily due to expenses related to the Company’s Retention Payment Plan and higher professional fees associated with legal and regulatory

compliance. The Company also recognized a non-cash $1.0 million deemed dividend due to the beneficial conversion feature on the Series D convertible preferred stock. In addition, the increase in net loss attributable to common stockholders was due to lower non-cash income from the change in the fair value of the Company’s warrant liability, which was zero for the three months ended September 30, 2016 compared to $2.6 million for the three months ended September 30, 2015. The change in the fair value of warrant liability was due to the expiration of September 2010 warrants, which expired in October 2015.

• Net loss attributable to common stockholders for the nine months ended September 30, 2016 was $49.8 million, or $0.46 per basic and diluted share, compared with a net loss attributable to common stockholders of $23.5 million, or $0.24 per basic and diluted share, for the comparable period in 2015. The increase in net loss attributable to common stockholders for the nine months ended September 30, 2016 was primarily due to the intangible asset impairment charge of $19.7 million during the nine months ended September 30, 2016, which was the result of the mutual termination of the STC.UNM agreement. In addition, the increase in net loss attributable to common stockholders was due to increases in research and development expenses of $3.4 million primarily due to greater activity related to the development of the Company’s product candidates, and increases in general and administrative expenses of $7.5 million primarily related to the retirement and separation agreement that Cascadian entered into with its former chief executive officer in January 2016, expenses related to the Company’s Retention Payment Plan and higher professional fees associated with legal and regulatory compliance. The Company also recognized a non-cash $2.6 million deemed dividend due to the beneficial conversion feature on the Series D convertible preferred stock. The increase in the net loss attributable to common stockholders was partially offset by a $6.9 million tax benefit during the nine months ended September 30, 2016.

Financial Guidance
Cascadian Therapeutics believes the following financial guidance to be correct as of the date provided. Cascadian Therapeutics is providing this guidance as a convenience to investors and assumes no obligation to update it.
Cascadian Therapeutics currently expects cash used in operations in 2016 to be approximately $38.0 million to $40.0 million. With cash, cash equivalents and investments of $71.6 million as of September 30, 2016, Cascadian Therapeutics estimates that its cash, cash-equivalents and investments will be sufficient to fund operations for at least the next 12 months.

DelMar Pharmaceuticals Presents New VAL-083 Data at Two International Scientific Conferences

On November 7, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company and its research collaborators have presented data at two scientific conferences hosted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, DelMar Pharmaceuticals, NOV 7, 2016, View Source [SID1234516371]).

AACR DNA Repair: Tumor Development & Therapeutic Response Conference. On Friday, November 4, 2016, DelMar and its collaborators from the University of British Columbia Prostate Cancer Research Center presented an abstract entitled: "Dissecting the Molecular Mechanism of Dianhydrogalactitol (VAL-083) in Cancer Treatment."
AACR New Horizons in Cancer Research: Delivering Cures through Cancer Research. Also, on Friday, November 4, 2016, DelMar and its collaborators from the University of Texas MD Anderson Cancer Center and the University of British Columbia presented an abstract entitled: "Assessment of dianhydrogalactitol in the treatment of relapsed or refractory non-small cell lung cancer."
The presentations can be accessed on DelMar’s website at View Source

Jeffrey Bacha, DelMar’s chairman & CEO, stated, "We continue to make great strides in understanding how VAL-083 targets cancer cells."

The data demonstrate that, upon treatment, VAL-083 rapidly forms cross-links on the DNA of cancer cells leading to cell cycle arrest in the S/G2 phase and lethal double-strand DNA breaks. This mechanism is distinct from other alkylating agents used in the treatment of cancer such as temozolomide, nitrosoureas or platinum-based chemotherapy. Because VAL-083’s mechanism differs from the others it is not subject to the same resistance mechanisms and therefore may be used to treat patients whose tumors are resistant to other therapies.

"We are leveraging clinical validation from prior NCI-sponsored research with a modern understanding of VAL-083’s unique anti-cancer mechanism to diversify our product development portfolio into new indications such as lung and ovarian cancer," added Mr. Bacha.

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments.

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

The Company has completed a successful end of Phase II meeting with the US FDA and plans to advance VAL-083 into a pivotal clinical trial for GBM patients following bevacizumab failure. DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following bevacizumab (Avastin) failure compared to published literature where survival of approximately two to five months has been reported.

DelMar’s advanced development program will feature a single multi-center randomized Phase III study measuring survival outcomes compared to a "physicians’ choice" control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in the treatment of Avastin-failed GBM. The final pivotal trial design will be confirmed with the FDA following further discussions with the Company’s clinical advisors.

In addition to the pivotal trial, DelMar also plans to initiate two separate Phase II clinical trials in earlier-stage GBM patients.

In collaboration with the University of Texas MD Anderson Cancer Center: A non-comparative, biomarker-driven, Phase II study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 or CCNU improves overall survival at 9 months, compared to historical control in bevacizumab naïve patients. (clinicaltrials.gov identifier: NCT02717962)
In collaboration with Sun-Yat Sen University and Guangxi Wuzhou Pharmaceutical (Group) Co.: A single arm Phase II clinical trial to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy (XRT) and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high levels of MGMT.
DelMar believes that data from these clinical trials, if successful, will form the basis of a new paradigm in the treatment for all GBM patients who fail, or whose tumors exhibit features that make them unlikely to respond to currently available chemotherapy.

In addition to its clinical research in GBM, DelMar believes that its research supports a unique mechanism of action for VAL-083 and that these data support the potential of VAL-083 as a new chemotherapy that may offer improved outcomes in the treatment of GBM and other solid tumors in patients whose tumors have failed or exhibit features that make them resistant to or unlikely to respond to current standard-of-care chemotherapy.

The company and its collaborators from the University of Texas MD Anderson Cancer Center recently presented data at the 11th Biennial Ovarian Cancer Research Symposium demonstrating that VAL-083 was able to overcome cisplatin-resistance in ovarian cancer cell lines with known p53 mutations and displays synergy with both cisplatin and AstraZeneca’s PARP inhibitor Olaparib against ovarian cancer in vitro.

Caladrius Biosciences Reports 2016 Third Quarter Financial Results

On November 7, 2016 Caladrius Biosciences, Inc. (NASDAQ:CLBS) ("Caladrius" or the "Company"), a cell therapy company combining an industry-leading development and manufacturing services provider through its subsidiary PCT, LLC a Caladrius Company ("PCT") with a select therapeutic development pipeline, reported financial results for the three and nine months ended September 30, 2016 (Filing, Q3, Caladrius Biosciences, 2016, NOV 7, 2016, View Source [SID1234516370]).
Business and financial highlights for the third quarter of 2016 and recent weeks include:
•
Achieved total quarterly revenues of $9.3 million, up 58% compared with $5.9 million for the third quarter of 2015;
•
Received Fast Track designation from the U.S. Food and Drug Administration (FDA) for CLBS03 (autologous expanded regulatory T cells, or Tregs) for the treatment of type 1 diabetes (T1D), making it the first known therapeutic candidate for the treatment of T1D to receive the designation;
•
Completed enrollment of the first patient cohort of The Sanford Project: T-Rex Study, the Company’s Phase 2 clinical trial of CLBS03 for the treatment of recent-onset T1D in adolescents;
•
Received a favorable recommendation from the independent Data Safety Monitoring Board (DSMB) to proceed with enrollment of the second cohort of the T-Rex Study following the safety evaluation of the first cohort of 19 patients;
•
Entered into a new five-year strategic manufacturing services agreement under which PCT will produce SPEAR T-cell therapies for Adaptimmune Therapeutics plc; and
•
Entered into agreements with several accredited investors, including previous investors and strategic collaborator Sanford Health, to sell up to $25 million in common equity priced at market without warrants.
Management Commentary
"Throughout 2016, we consistently increased revenues at our PCT subsidiary and are poised to achieve our stated goal of 2016 annual revenue in excess of $30 million, which represents annual growth of more than 30%. In addition, year-to-date we secured over $50 million in strategic and/or committed financings, about half of which was non-dilutive with the remainder under favorable terms relative to the market rates for companies like ours. We also paid back to our lender over $9 million of long-term debt, significantly reduced our operating expenses and monetized non-core assets, all while advancing our key immune modulation program’s Phase 2 clinical study of CLBS03 to treat T1D," stated David J. Mazzo, Ph.D., Chief Executive Officer of Caladrius.
"We are particularly pleased with the progress of The Sanford Project: T-Rex Study in T1D. We completed enrollment of the first cohort of 19 patients and were delighted that the DSMB recommended continuation of the study based on a favorable safety assessment. We have begun enrolling patients into the second cohort of this 111-patient study earlier than originally expected and plan to reach the 50% enrollment mark in mid-2017. Enrollment of the 70th patient, which triggers an $8.4 million capital infusion under the terms of the September private placements, is expected to occur shortly thereafter. We continue to benefit from the support of Sanford Research. In addition to their equity investment, Sanford has agreed to extend operational support at their clinical sites for the remainder of the study. We continue to be excited by the promise of CLBS03, a novel therapeutic being developed to address the significant unmet medical need in this chronic disease that affects children and young adults. We have made significant achievements across a number of key areas that we believe position Caladrius for continued growth and success throughout the balance of 2016 and beyond," concluded Dr. Mazzo.
Third Quarter Financial Highlights
Total revenues for the third quarter of 2016 increased 58% to $9.3 million compared with $5.9 million for the third quarter of 2015 and increased 12% compared with $8.3 million for the second quarter of 2016. Gross margin on revenues was 8% in the third quarter of 2016 compared with 18% in the third quarter of 2015, directly impacted by the non-payment of approximately $600,000 in billings for work the Company performed and billed to a single customer during the third quarter of 2016, which customer is currently experiencing financial difficulties. Accordingly, the Company has delayed revenue recognition until such time as payment is reasonably assured. The Company continues to work with this client to obtain payment and will recognize any such receipts as revenue in the periods received.

Research and development (R&D) expenses for the third quarter of 2016 decreased 58% to $2.6 million compared with $6.3 million for the third quarter of 2015. The majority of current quarter expenses were dedicated to the Company’s immune modulation platform and, specifically, costs related to the T-Rex Study. The decline in R&D expenses over the prior year quarter was primarily related to the discontinuation of non-core R&D programs announced at the beginning of 2016 and related reductions in R&D staffing and departmental costs.
Selling, general and administrative (SG&A) expenses for the three months ended September 30, 2016 were $4.9 million, a small reduction from $5.1 million reported for the same period in 2015. This reflected significantly lower operational and compensation-related costs during the current year quarter compared with the prior year quarter, partially offset by higher equity-based compensation expenses compared with the prior year quarter.
The operating loss for the third quarter of 2016 was $6.9 million compared with an operating loss of $10.4 million for the third quarter of 2015, reflecting higher revenues and lower R&D expenses.
The Company reported a net loss attributable to Caladrius common stockholders for the third quarter of 2016 of $6.9 million, or $1.09 per share, compared with a net loss attributable to Caladrius common stockholders for the third quarter of 2015 of $11.4 million, or $2.06 per share.
Nine Month Financial Highlights
Total revenues for the nine months ended September 30, 2016 increased 68% to $25.1 million compared with $14.9 million for the first nine months of 2015. Gross margin for the first nine months of 2016 was 13% compared with 6% for the first nine months of 2015.
R&D expenses for the first nine months of 2016 decreased to $12.5 million compared with $20.7 million for the first nine months of 2015. The decline in R&D expenses over the first nine months of 2015 was primarily related to the discontinuation of non-core R&D programs announced at the beginning of 2016 and related reductions in R&D staffing and departmental costs.
SG&A expenses decreased to $16.1 million for the first nine months of 2016 compared with $25.0 million for the same period in 2015. This reflected operational and compensation-related cost reductions, as well as equity-based compensation expenses that were significantly below the prior year SG&A expense levels.
The operating loss for the first nine months of 2016 was $25.4 million compared with an operating loss of $54.1 million for the first nine months of 2015.
The net loss attributable to Caladrius common stockholders for the nine months ended September 30, 2016 was $26.7 million, or $4.45 per share, compared with a net loss attributable to Caladrius common stockholders for the nine months ended September 30, 2015 of $47.7 million, or $10.40 per share.
Balance Sheet and Cash Flow Highlights
As of September 30, 2016, Caladrius had cash and cash equivalents of $18.6 million, which included $10.6 million received from the previously announced equity financing in September 2016 and the payment of $3.0 million to Oxford Finance LLC for repayment of long-term debt. Net cash used in operating activities for the nine months ended September 30, 2016 was $20.3 million, compared with $30.5 million for the nine months ended September 30, 2015. Caladrius also invested $2.3 million in capital expenditures, primarily related to improvements to PCT’s Allendale, N.J. manufacturing facility.
2016 Financial Guidance
The Company updates its previous 2016 guidance as follows:
•
Consolidated 2016 Annual Revenues: affirms guidance to exceed $30 million or a greater than 30% increase compared with 2015.
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Capital Improvements at PCT’s Allendale, N.J. Facility: affirms guidance that improvements will be completed in 2017, and updates guidance that approximately $2 million will be spent in calendar 2016. Overall cost to complete capital improvements in 2017, including the implementation of commercial grade quality systems, to be provided when 2017 guidance is announced.
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CLBS03 Phase 2 Study Costs in 2016: affirms guidance of $6 million to $7 million.
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Consolidated 2016 Operating Activities Cash Burn: affirms guidance of $25 million to $28 million, or between $5 million and $8 million in the fourth quarter of 2016, but with a trend toward the lower end of the range.

ChemoCentryx Reports Third Quarter 2016 Financial Results and Provides Corporate Update

On November 7, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), reported financial results for the third quarter ended September 30, 2016 and provided an update on the Company’s clinical development activities (Press release, ChemoCentryx, NOV 7, 2016, View Source [SID1234516363]).

"We have made significant progress in our orphan and rare diseases portfolio — building upon our positive Phase II results in the CLEAR and CLASSIC trials in ANCA vasculitis earlier this year, we have also reported positive results in the aHUS pilot Phase II study, as well as improvement of renal function in a C3G patient who had few, if any, other treatment options. All of this provides mounting evidence that avacopan has the potential to change treatment paradigms in these rare and debilitating diseases," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "With avacopan in AAV, we continue to make progress regarding our regulatory discussions and remain on track to initiate our Phase III development program by the end of this year. Our scientific approach forms the foundation of a broad pipeline of promising chemoattractant-based drug candidates which we believe will transform patient care."

Pipeline Developments Across Key Therapeutic Areas

Orphan and Rare Diseases: Avacopan, an orally-administered complement inhibitor targeting the C5a receptor (C5aR), is the cornerstone of an orphan and rare diseases portfolio addressing multiple unmet medical needs. These diseases include ANCA vasculitis (AAV), atypical Hemolytic Uremic Syndrome (aHUS) and Complement 3 Glomerulopathy (C3G). Avacopan acts by blocking the destructive action of neutrophils that are activated as a consequence of the complement protein known as C5a binding to C5aR on neutrophils during autoimmune inflammatory events including the destruction of blood vessels in AAV.

Announced positive data from a pilot Phase II study designed to assess the effects of orally-administered avacopan on thrombus formation from the serum of aHUS patients with end-stage renal disease. The aHUS patients in the study are on stable chronic hemo-or peritoneal dialysis. Avacopan (30 mg) was administered twice daily for two weeks. Five patients have been treated to date. Highlights of the presentation that will take place at the American Society of Nephrology (ASN) Kidney Week 2016 include:
After 14 days of dosing the mean decrease in thrombus size was 83%. Three patients showed 100% inhibition of thrombus formation and one patient showed greater than 30% inhibition. Additionally, one patient who received only two days of avacopan treatment showed greater than 30% inhibition at that time;
Treatment appeared to be mechanism specific: when avacopan treatment was stopped, the thrombus size returned to pre-treatment levels; and
Avacopan treatment appeared to be safe; there was one serious adverse event, not considered related to avacopan use, in a patient with long-standing cardiovascular and renal disease of cardiac asystole.
Reported improvement in renal physiology and stabilization in renal function following treatment with avacopan in a patient with refractory C3G. Under a "Special Needs" protocol (similar to the compassionate use program in the United States), a C3G renal transplant recipient with deteriorating kidney function responded well to treatment with avacopan. Prior to receiving treatment with avacopan, the C3G patient had received treatment with a wide spectrum of immunosuppressant drugs including rituximab, cyclophosphamide, mycophenolate mofetil, tacrolimus and glucocorticosteroids, all of which had failed to prevent disease recurrence or progression. Highlights of the results are as follows:
After one month of avacopan treatment, renal function, based on estimated glomerular filtration rate (eGFR) stabilized, and has remained stable for over a year. Decline in a patient’s eGFR is a negative and often life-threatening effect of C3G;
Sequential kidney biopsies taken after the patient had been on avacopan for two and seven months showed continued improvement in kidney histology based on a decrease in glomerular endocapillary proliferation and a marked reduction in the number of glomerular inflammatory macrophages, as compared to the pre-treatment biopsy; and
Avacopan was shown to be safe and well tolerated. The patient has now entered month 15 of treatment and continues to tolerate avacopan well with no serious adverse events.
Conducted End-of-Phase II and scientific advice meetings with U.S. and EU regulatory agencies, respectively, regarding the avacopan AAV Phase III development plan.
Immuno-Oncology and Other Therapeutic Areas: CCX872 is a selective inhibitor of the chemokine receptor known as CCR2, and is designed to block the infiltration of immune suppressor cells in the tumor microenvironment. CCX872 is being evaluated in patients with non-resectable pancreatic cancer in an ongoing, multi-center clinical trial. The primary outcome measurement of the study is progression-free survival (PFS) after at least 24 weeks of treatment. The Company’s immuno-oncology efforts include research to identify potential drug candidates targeting additional receptors that are believed to play an important role in the tumor microenvironment. Inhibiting CCR2 may be effective in therapeutic areas beyond immuno-oncology, including decreasing inflammatory macrophage infiltration into the liver, thus reducing hepatic inflammation and fibrosis.

Presented data at the American College of Gastroenterology (ACG) 2016 Annual Meeting demonstrating that treatment with CCX872 reduced hepatic inflammation, steatosis, and scarring in models of non-alcoholic steatohepatitis (NASH). Highlights of the results are as follows:
Two models of NASH were used to determine the efficacy of CCX872 in reducing fibrosis; in both models, treatment with CCX872 achieved a statistically significant reduction in liver fibrosis as compared to placebo control;
CCX872 was more efficacious than a CCR2/CCR5 dual inhibitor, being advanced elsewhere in clinical development, in reducing liver fibrosis in a model which is known to induce NASH;
Reported initial 12 week overall response rate (ORR) results from an ongoing open label, single arm Phase Ib clinical trial with CCX872 in patients with advanced pancreatic cancer; and
Presented preclinical data at the CRI-CIMT-EATI-AACR 2016 Annual Meeting demonstrating that blocking CCR2 with CCX872 decreases tumor burden by blocking monocyte infiltration, creating a microenvironment that is more favorable for CD8+ T-cell activity. This provides a mechanistic rationale for investigating the combination of CCX872 and an immune checkpoint inhibitor for the treatment of pancreatic cancer.
Corporate Development

Announced the appointment of Henry A. McKinnell, Jr., Ph.D., retired chairman and chief executive officer of Pfizer Inc., to our Board of Directors. Dr. McKinnell brings significant leadership in operations and international strategic alliances, as well as commercial experience to ChemoCentryx.
Anticipated Milestones

Orphan and Rare Diseases:

Present detailed results from the Phase II CLEAR and CLASSIC trials of avacopan in AAV in oral presentations at ASN Kidney Week and the American College of Rheumatology (ACR) 2016 Annual Meeting, respectively;
Present results from the pilot Phase II study of avacopan in aHUS patients with end-stage renal disease at ASN Kidney Week;
Present CRISPR-Cas9 data at ASN Kidney Week, which include details of the creation of a colony of genetically unique mice that are designed to assess the effects of inhibiting the C5aR with avacopan on diseases characterized by unregulated complement activation, such as aHUS and C3G;
Finalize development plan and initiate Phase III development program of avacopan for the treatment of AAV by year end;
Initiate a clinical endpoint study with avacopan in patients with C3G in the first half of 2017; and
Initiate a clinical endpoint study with avacopan in patients with aHUS in 2017.
Immuno-Oncology and Other Therapeutic Areas:

Report PFS data from pancreatic cancer trial of CCX872 in combination with FOLFIRINOX early in the first quarter of 2017, potentially at a major medical meeting; and
Initiate a Phase II trial with CCX872 in combination with a checkpoint inhibitor in 2017.
Third Quarter 2016 Financial Results and Outlook

Cash, cash equivalents and investments totaled $131.6 million at September 30, 2016.

Revenue was $4.1 million for the three months ended September 30, 2016 compared to zero in the same period in 2015. The increase in revenue from 2015 to 2016 was due to: (i) amortization of the upfront payment from Vifor Pharma pursuant to the avacopan agreement and (ii) grant revenue from the FDA to support the clinical development of avacopan for the treatment of patients with AAV.

Research and development expenses were $8.4 million for the three months ended September 30, 2016 compared to $7.9 million reported for the same period in 2015. The increase in research and development expenses from 2015 to 2016 was primarily attributable to higher expenses associated with avacopan for start-up activities related to the Phase III development program in patients with AAV. This increase was partially offset by lower expenses associated with Phase II development of avacopan, due to the completion of the CLEAR and CLASSIC Phase II clinical trials in 2016.

General and administrative expenses were $3.2 million for the three months ended September 30, 2016 compared to $3.8 million for the comparable period in 2015. The decrease from 2015 to 2016 was primarily due to lower stock-based compensation and intellectual property filing expenses.

Net loss was $7.1 million for the second quarter ended September 30, 2016 compared to $11.7 million in the same period in 2015.

Total shares outstanding at September 30, 2016 were approximately 47.8 million shares.