On June 30, 2015 Telesta Therapeutics Inc. (TSX: TST) (PNK: BNHLF) reported that it has submitted electronically, through its U.S. agent, a Biologics License Application (BLA) to the United States Food and Drug Administration (FDA) for MCNA1 (Press release, Telesta Therapeutics, JUN 30, 2015, View Source [SID:1234507864]). MCNA is Telesta’s novel biologic immunotherapeutic for the treatment of high-risk non-muscle invasive bladder cancer patients who have failed first-line BCG therapy.

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Telesta also announced today that they have received from the FDA a waiver exempting Telesta from the payment of the $US2.3 million BLA application fee.

The FDA has a 60-day filing review period to determine whether Telesta’s BLA submission for MCNA is complete and acceptable for filing, whether MCNA will be designated for priority review or standard review and whether an advisory committee meeting will be scheduled. Their decisions on these items will be communicated to Telesta in the FDA’s official filing communication known as the "Day-74 letter". Telesta will communicate the FDA’s filing decisions upon receipt.

Telesta’s BLA submission has been made following extensive and ongoing dialogue with the US FDA, including a formal pre-BLA meeting in November, 2014 and a Type C facility meeting in February, 2015. As part of this process, Telesta has incorporated the FDA’s recommendations into the current submission and the Company has also been working with top tier regulatory consultants to ensure that their BLA submission meets all current regulatory requirements.

Concurrently with this BLA submission, Telesta confirmed the completion of a number of upgrades and improvements to Telesta’s manufacturing facility and operating procedures, undertaken following recommendations received from the FDA at the Type C facility meeting held in February. As previously announced, these improvements were implemented by Telesta to ensure that their manufacturing facility is well positioned for the FDA pre-approval inspection that will take place as part of the FDA’s formal review process.

"The BLA submission for MCNA marks an major step towards our ultimate goal of providing bladder cancer patients and the medical professionals in the urology community, with a therapeutic alternative to radical cystectomy," said Dr. Michael Berendt, CEO & Chief Scientist of Telesta Therapeutics. "There is an urgent and unmet medical need to develop new therapies for bladder cancer patients who have not seen new therapies approved for almost 20 years. I am incredibly proud of Telesta’s dedicated and talented employees, many of whom have been working for more than a decade to advance this important therapeutic agent, for their hard work and professionalism that has permitted us to achieve this key corporate milestone."

Current practice guidelines for the treatment of high-risk non-muscle invasive bladder cancer patients who are refractory to or have relapsed from first line BCG therapy call for radical cystectomy (surgical removal of the bladder and adjacent organs). MCNA was developed to provide a much-needed therapeutic option for these patients. This BLA submission is the first step towards the potential regulatory approval and commercialization of MCNA, which could become the first approved therapeutic alternative for these high-risk bladder cancer patients since 1998. The approval of MCNA in the U.S. could occur as early as Q1/2016 should the FDA designate the MCNA BLA submission for priority review.

About MCNA

Telesta’s MCNA is a biologic therapy derived from the cell wall fractionation of a non-pathogenic bacteria. Its activity is believed to be through a dual mechanism of immune stimulation and direct anti-cancer effects. MCNA was developed to be delivered as a sterile suspension for intravesical administration by urologists and urology nurses, following the same dosing paradigm as first-line BCG therapy, with the advantage that it can be prepared, handled and disposed of easily and safely. The efficacy, duration of responses and safety data from MCNA’s pivotal Phase 3 trial were recently published in the Journal of Urology2. Telesta continues to prosecute novel composition of matter, methods of use and manufacturing patents in most regions of the world and recently announced the granting of the key composition of matter patent in the United States providing intellectual property coverage of MCNA to 2031.

A recent commercial assessment, conducted by Medical Marketing Economics ("MME"), a global leader in the development of value-based strategies and market research, employed rigorous qualitative and quantitative primary market research with payers (managed care organizations/decision makers both from the private and public sector) and over 100 urologists (community urologists and key opinion leaders), to define market size, pricing strategy and market access context as well as reimbursement potential for MCNA. This study confirmed a commercial U.S. market opportunity of more than $400 million and clearly established that the target product profile of MCNA represents an extremely interesting therapeutic option for practicing urologists.

About Telesta Therapeutics Inc.

Telesta Therapeutics Inc. is a late stage therapeutics company with near term commercial potential focused on the manufacturing, marketing and licensing/acquisition of proprietary and innovative therapies for the global health market. The Company’s primary goal is to develop and commercialize products that advance human health and increase shareholder value. For more information, please visit www.telestatherapeutics.com

On June 29, 2015 Merck reported results from a Phase 3 study investigating the safety and efficacy of single-dose EMEND (fosaprepitant dimeglumine) for Injection, Merck’s substance P/neurokinin (NK-1) receptor antagonist, in combination with other anti-vomiting medicines, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in adult cancer patients receiving moderately emetogenic (vomit-inducing) chemotherapy (MEC) (Press release, Merck & Co, JUN 29, 2015, View Source [SID:1234506001]). In the study, the first to evaluate an intravenous NK-1 receptor antagonist for the prevention of CINV associated with MEC, the single-dose EMEND for Injection regimen provided greater protection from nausea and vomiting following administration of chemotherapy versus an active control of placebo with other anti-vomiting medicines. These data were presented in an oral session at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting on Supportive Care in Cancer (Abstract #27-02-O) in Copenhagen (June 25-27, 2015).

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"The results from this important Phase 3 trial are very encouraging as they are the first study to evaluate EMEND for Injection in a combination regimen for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy – and show the potential to use a single day antiemetic regimen," said Dr. Bernardo L. Rapoport, principal investigator for the study and chief medical oncologist, Medical Oncology Centre of Rosebank, Johannesburg, South Africa.

"Nausea and vomiting remain a significant burden for patients receiving chemotherapy and we look forward to submitting these data for EMEND for Injection to the U.S. Food and Drug Administration," said Stuart Green, vice president, clinical research, Merck Research Laboratories. "This study builds on our decade of research for EMEND and Merck’s overall commitment to help people with cancer."

EMEND for Injection, a substance P/Neurokinin-1 (NK1) receptor antagonist approved for use in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer (HEC) chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of MEC. EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended.

In the U.S., the single-dose regimen of EMEND for Injection is approved for use associated with HEC. Merck plans to submit these recent data to the Food and Drug Administration in the second half of 2015 to seek approval for a regimen containing single-dose EMEND for Injection for the prevention of CINV associated with MEC.

About Phase 3 Study for Single-Dose EMEND for Injection in MEC

In this global randomized, Phase 3, double-blind study, more than 1,000 patients receiving MEC were randomly assigned to receive either single-dose EMEND for Injection (150 mg) in combination with ondansetron capsules (16 mg) and dexamethasone capsules (12 mg) (n=504) on day one (followed by oral placebo for ondansetron on days two and three) or an active control regimen consisting of placebo (saline IV) in combination with ondansetron (16 mg) and dexamethasone (20 mg) (n=497) on day one (followed by 8 mg ondansetron on days two and three). The primary endpoint of the study was complete response (CR) (as measured by no vomiting and no use of rescue medication for nausea or vomiting) in the delayed phase (25 to 120 hours following initiation of chemotherapy). The secondary endpoints were CR after the first dose of chemotherapy in the acute phase (0 to 24 hours) and in the overall phase (0-120 hours), as well as no vomiting in the overall phase.

Single-Dose EMEND for Injection Regimen Achieved Superior Control of CINV

For the primary study endpoint, EMEND for Injection regimen provided higher incidence of CR in days 2 through 5 – with CR observed in 78.9 percent of patients receiving the EMEND for Injection regimen versus 68.5 percent in the active control group (p <0.001). For the secondary endpoints, in the acute phase, CR was observed in 93.2 percent of patients receiving the EMEND for Injection regimen versus 91 percent in the active control group (p = 0.184). In the overall phase, the incidence of CR was observed in 77.1 percent of patients receiving the EMEND for Injection regimen versus 66.9 percent in the active control group (p <0.001). Additionally, a significantly greater proportion of patients receiving the EMEND for Injection regimen experienced no vomiting in the overall phase (82.7 percent with EMEND vs 72.9 percent in the active control group) and delayed phase (83.9 percent with EMEND vs 75.1 percent in the active control group) (both p <0.001) – with a favorable trend in the acute phase (94.8 percent with EMEND vs 92 percent in the active control group).

The most common adverse events (across all grades) in the EMEND for Injection regimen and active control group included fatigue (15.1 percent and 12.9 percent), diarrhea (12.7 percent and 11.3 percent), and constipation (9.3 percent and 10.5 percent). Treatment-related adverse events were observed in 8.5 percent of patients receiving the EMEND for Injection regimen and in 9.1 percent of patients in the active control group. Serious treatment-related adverse events were observed in 0.2 percent of patients receiving the EMEND for Injection regimen and in 0.4 percent of patients in the active control group.

Selected Important Safety Information for EMEND (fosaprepitant dimeglumine) For Injection

EMEND for Injection is contraindicated in patients who are hypersensitive to EMEND for Injection, aprepitant, polysorbate 80, or any other components of the product. Known hypersensitivity reactions include flushing, erythema, dyspnea, and anaphylactic reactions.

Aprepitant, when administered orally, is a moderate cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitor. Because fosaprepitant is rapidly converted to aprepitant, neither drug should be used concurrently with pimozide or cisapride. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

EMEND for Injection should be used with caution in patients receiving concomitant medications, including chemotherapy agents that are primarily metabolized through CYP3A4. Inhibition of CYP3A4 by EMEND for Injection could result in elevated plasma concentrations of these concomitant medications. Conversely, when EMEND for Injection is used concomitantly with another CYP3A4 inhibitor, aprepitant plasma concentrations could be elevated. When EMEND for Injection is used concomitantly with medications that induce CYP3A4 activity, aprepitant plasma concentrations could be reduced, and this may result in decreased efficacy of aprepitant.

Chemotherapy agents that are known to be metabolized by CYP3A4 include docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine. In clinical studies, EMEND was administered commonly with etoposide, vinorelbine, or paclitaxel. The doses of these agents were not adjusted to account for potential drug interactions. In separate pharmacokinetic studies, EMEND did not influence the pharmacokinetics of docetaxel or vinorelbine.

Because a small number of patients in clinical studies received the CYP3A4 substrates vinblastine, vincristine, or ifosfamide, particular caution and careful monitoring are advised in patients receiving these agents or other chemotherapy agents metabolized primarily by CYP3A4 that were not studied.

There have been isolated reports of immediate hypersensitivity reactions, including flushing, erythema, dyspnea, and anaphylaxis, during infusion of fosaprepitant. These hypersensitivity reactions have generally responded to discontinuation of the infusion and administration of appropriate therapy. It is not recommended to reinitiate the infusion in patients who have experienced these symptoms during first-time use.

Coadministration of EMEND for Injection with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of EMEND for Injection with each chemotherapy cycle.

The efficacy of hormonal contraceptives (including birth control pills, skin patches, implants, and certain IUDs) may be reduced during coadministration with and for 28 days after the last dose of EMEND for Injection. Alternative or backup methods of contraception should be used during treatment with and for 1 month after the last dose of EMEND for Injection.

Chronic continuous use of EMEND for Injection for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during chronic continuous use.

In clinical trials of EMEND in patients receiving HEC, the most common adverse events reported at a frequency greater than with standard therapy, and at an incidence of 1% or greater, were hiccups (4.6% EMEND vs 2.9% standard therapy), asthenia/fatigue (2.9% vs 1.6%), increased ALT (2.8% vs 1.5%), increased AST (1.1% vs 0.9%), constipation (2.2% vs 2.0%), dyspepsia (1.5% vs 0.7%), diarrhea (1.1% vs 0.9%), headache (2.2% vs 1.8%), and anorexia (2.0% vs 0.5%).

In a clinical trial evaluating safety of the 1-day regimen of EMEND for Injection compared with the 3-day regimen of EMEND, the safety profile was generally similar to that seen in prior HEC studies with aprepitant. However, infusion-site reactions occurred at a higher incidence in patients who received fosaprepitant (3.0%) than in those who received aprepitant (0.5%). Those infusion-site reactions included infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration, and infusion-site thrombophlebitis.

About Chemotherapy Induced Nausea and Vomiting (CINV)

Chemotherapy Induced Nausea and Vomiting (CINV) is a common side effect of chemotherapy caused by injured stomach cells that start the process of nausea and vomiting and can directly activate the area of the brain responsible for producing nausea and vomiting. The two main types of CINV are acute and delayed. Acute happens within the first 24 hours of receiving chemotherapy. Delayed happens from day 2 to day 5 after chemotherapy. The amount and timing of CINV can vary. Some chemotherapies cause acute nausea and vomiting. Others cause acute nausea and vomiting followed by another period of delayed nausea and vomiting.

On June 29, 2015 Cellular Biomedicine Group reported it has completed the previously announced acquisition of Blackbird Bio Finance and University of South Florida’s ("Licensor") next generation GVAX vaccine’s ("CD40LGVAX") related technologies and technical knowledge (Press release, Cellular Biomedicine Group, JUN 29, 2015, View Source [SID:1234506003]). With the close of this acquisition, management believes that the Company will be able to offer comprehensive immuno-oncology cell therapy portfolios, as well as a broad set of options for patients.

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Dr. William (Wei) Cao, Chief Executive Officer of CBMG, commented: "We are extremely pleased with this strategic acquisition which strengthens our cancer immunotherapy vaccine and vaccine combination technology platform. This inroad into the U.S. market is a significant milestone for the Company and we look forward to seeking approval to conduct international clinical trials with leading medical centers."

Under the terms of the agreement, CBMG will pay an initial consideration of $2.5 million in cash and up to $1.75 million in shares of the Company’s Common Stock, which is based on the 20-day volume, weighted average price ("VWAP") of the Company’s Common Stock on the closing date of June 26, 2015. As a licensee of CD40LGVAX, the Company could pay potentially more than $25M in future milestone and sales royalty payments to the Licensor. Additional information can be found in the Form 8-K filed by Cellular Biomedicine Group with the Securities and Exchange Commission on June 12, 2015.

On June 29, 2015 Epizyme reported that updated data from the phase 1 portion of its ongoing phase 1/2 study of tazemetostat will be presented during the European Cancer Congress 2015, hosted by the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper), to be held in Vienna, Austria, September 25-28, 2015 (Press release, Epizyme, JUN 29, 2015, View Source [SID:1234506010]). Tazemetostat is a first-in-class EZH2 inhibitor that Epizyme is currently studying in patients with relapsed or refractory B-cell non-Hodgkin lymphomas (NHL) and advanced solid tumors, including INI1-deficient tumors.

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A Phase 1 Study of EPZ-6438 (E7438), an Enhancer of Zeste-Homolog 2 (EZH2)
Inhibitor: Preliminary Activity in INI1-negative Tumors
Speaker: Antonine Italiano, M.D., Ph.D., Institut Bergonié, Bourdeaux, France
Session Title: Proffered Paper Session: Early Drug Development (Hall C1)
Session Date/Time: Saturday, September 26, 10:30 a.m. -12:30 p.m. CET

About EZH2 in Cancer
EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphomas, INI1-deficient cancers such as malignant rhabdoid tumors, epithelioid sarcomas and synovial sarcoma; and a range of other solid tumors.

About Tazemetostat
Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-6438.

Tazemetostat is the second HMT inhibitor to enter human clinical development (following Epizyme’s DOT1L inhibitor, pinometostat, also known as EPZ-5676).

Additional information about this program, including clinical trial information, may be found here: View Source

On June 29, 2015 Cellular Biomedicine Group reported it has completed the previously announced acquisition of Blackbird Bio Finance and University of South Florida’s ("Licensor") next generation GVAX vaccine’s ("CD40LGVAX") related technologies and technical knowledge (Filing, 8-K, Cellular Biomedicine Group, JUN 29, 2015, View Source [SID:1234506026]). With the close of this acquisition, management believes that the Company will be able to offer comprehensive immuno-oncology cell therapy portfolios, as well as a broad set of options for patients.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Dr. William (Wei) Cao, Chief Executive Officer of CBMG, commented: "We are extremely pleased with this strategic acquisition which strengthens our cancer immunotherapy vaccine and vaccine combination technology platform. This inroad into the U.S. market is a significant strategic milestone for the Company and we look forward to seeking approval to conduct international clinical trials with leading medical centers."

Under the terms of the agreement, CBMG will pay an initial consideration of $2.5 million in cash and up to $1.75 million in shares of the Company’s Common Stock which is based on the 20-day volume weighted average price ("VWAP") of the Company’s Common Stock on the closing date of June 29, 2015. As a licensee of CD40LGVAX, the Company could pay potentially more than $25M in future milestone and sales royalty payments to the Licensor. Additional information can be found in the Form 8-K filed by Cellular Biomedicine Group with the Securities and Exchange Commission on June 12, 2015.