On November 16, 2016 Therapeutic Proteins International (TPI) reported that it will change its name to Adello Biologics, LLC, effective immediately (Press release, Therapeutic Proteins International, NOV 16, 2016, View Source;s%20Interest-,Therapeutic%20Proteins%20International%20Renames%20Company%20to%20Adello%20Biologics%2C%20LLC%3B%20Relocates,Headquarters%20to%20Piscataway%2C%20New%20Jersey&text=CHICAGO%2C%20Nov.,Biologics%2C%20LLC%2C%20effective%20immediately [SID1234563291]). The name change accompanies the move of its corporate headquarters to Piscataway, New Jersey. Along with all corporate functions, the 50,000 sq. ft. facility will house the company’s new R&D lab. The company plans to complete the move by the end of the year.

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"The new name aligns with our company’s vision; To become the trusted choice of high-quality, affordable biosimilars for patients worldwide," said Dr. Peter Moesta, Chief Executive Officer of Adello. "We are fully focused on developing a robust portfolio of biosimilars, and our move to New Jersey is an effort to further enhance our R&D bench strength, drawing on the scientific talent pool in the area."

The Chicago site will remain the company’s key manufacturing facility in the U.S. with around 100 employees supporting operations. Adello is currently actively recruiting positions for the R&D function in Piscataway. With capacity for 70 scientists, the group will continue to be led by Chief Scientific Officer, Dr. Michael Washabaugh.

On November 16, 2016 PharmaCyte Biotech (OTCQB: PMCB) reported that it has arrived at the door of U.S. FDA and awaits a pre-IND meeting with the agency (Press release, PharmaCyte Biotech, NOV 16, 2016, View Source [SID1234516661]). After years of surrounding its signature live-cell encapsulation technology, Cell-in-a-Box, with some of the brightest minds in pancreatic cancer and fine-tuning its therapy and clinical trial design, the small biotech has reached the final test before it can begin its pivotal clinical trial in advanced pancreatic cancer.

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PharmaCyte made two recent announcements that would be big for any company, but for a small biotech, the announcements are big news for shareholders who have been patiently waiting. First, it announced that oncologist, Dr. Manuel Hidalgo, who is the Chief of the Division of Hematology-Oncology at Harvard Medical School’s Beth Israel Deaconess Medical Center, has accepted the role of Principal Investigator for PharmaCyte’s planned clinical trial. And the company followed up that news with the announcement that it has requested a pre-IND meeting with the FDA for its upcoming pancreatic cancer clinical trial.

In PharmaCyte’s clinical trial, Dr. Hidalgo will once again be teamed up with renowned pancreatic cancer expert Dr. Daniel Von Hoff. Dr. Von Hoff is the Chief Development Officer at Translational Drug Development (TD2), the nation’s premiere oncology CRO and the company responsible for organizing and conducting PharmaCyte’s clinical trial.

Dr. Von Hoff and Dr. Hidalgo worked together on the clinical trials that brought the industry what is now the gold standard and the FDA approved treatment for advanced pancreatic cancer, Abraxane plus gemcitabine.

PharmaCyte has already named a handful of clinical trial sites that are being considered which include the Mayo Clinic in Scottsdale, Arizona, the Beth Israel Deaconess Cancer Center in Boston, the Dana-Farber Cancer Institute in Boston, the Baylor Cancer Center in Dallas, the City of Hope Cancer Center in Los Angeles and sites in Germany and Spain.

Creating an "Artificial Liver" to Target Pancreatic Cancer

PharmaCyte’s pancreatic cancer therapy is made up of pinhead-sized, porous capsules that are filled with thousands of genetically modified cells that act as a type of "artificial liver."

PharmaCyte’s Cell-in-a-Box is not a drug delivery system. There are no drugs encapsulated inside the porous capsules for any of its treatments. Instead, the capsules are filled with about 10,000 live cells that are capable of converting an inactive chemotherapy drug (ifosfamide) into its active cancer-killing form — just as the enzyme system in a patient’s liver would normally do.

Because the chemotherapy drug ifosfamide is a prodrug or an inactive drug, it can travel all over the body and have no effect whatsoever until it is activated in the liver. PharmaCyte’s therapy essentially moves the "normal" conversion site of that inactive drug (the patient’s liver) closer to the cancerous tumor by using Cell-in-a-Box capsules and the live cells inside them to do the job of the patient’s liver or to act as an "artificial liver."

How Does PharmaCyte Biotech Do It

The encapsulated live cells (Cell-in-a-Box capsules) are placed as close to the patient’s cancerous tumor as possible. Once implanted, ifosfamide, the aforementioned chemotherapy drug that needs to be activated in the body, is given to the patient intravenously at one-third the normal dose. The ifosfamide is then carried by the circulatory system to where the encapsulated cells have been placed.

When the ifosfamide, which is normally activated in the liver, comes in contact with the encapsulated live cells in the Cell-in-a-Box capsules, the chemotherapy drug is activated into its cancer-killing form right at the site of the cancer. This is "targeted chemotherapy" in the truest sense, and the company’s therapy has proven effective and safe to use in past clinical trials.

Chemotherapy with No Side Effects

The obvious question is why move the conversion site of the chemotherapy drug at all. Well, there are actually a number of reasons to move the activation site closer to the tumor. We’ll start with the chemotherapy drug itself.

Ifosfamide, when activated, has a very short half-life (time before it decays and no longer offers any effect), so by using the cells inside the Cell-in-a-Box capsules to activate the drug at the site of the tumor, ifosfamide can immediately be the most effective when it’s the most potent before dying off minutes later.

Without a treatment like PharmaCyte’s, ifosfamide would be given to the patient intravenously and then activated "normally" in the liver, the activated drug would then affect tissues and organs other than the pancreas, and by the time it reached the pancreas, it undoubtedly would have lost much of its effectiveness. So, to be effective against a pancreatic tumor when the Cell-in-a-Box capsules are not used, a large dose of the drug has to be administered.

Using ifosfamide in such large doses has proven to be damaging for tissues and organs including the patient’s liver, and because the activated drug would come in contact with such other organs and good cells throughout the body on its way to the pancreas, the side effects would be intolerable; in fact, this is known to be the case.

By moving the conversion site as close to the tumor as possible, PharmaCyte is able to give a much smaller dose of the chemotherapy drug (one-third the normal dose), which patient’s are able to tolerate, and because of the smaller dose, the treatment can be administered without any side effects from the chemotherapy.

Next Stop FDA Clinical Trial

With a list of oncologists and clinicians that reads like a who’s who now in place to lead PharmaCyte’s clinical trial, the company is now awaiting a pre-IND meeting with the FDA. After submitting questions to the FDA as part of a pre-IND meeting request where aspects of the content of the Investigational New Drug (IND) application itself (CMC section, clinical trial description, etc.) will be discussed, PharmaCyte is ready to fully engage with the FDA on its way to receiving the final approval it needs to begin its planned clinical trial in pancreatic cancer.

Once PharmaCyte navigates the pre-IND process and files its IND application, then the FDA will have 30 days to make comments, and if no comments are made, then PharmaCyte is effectively "approved" to begin its pivotal clinical trial.

On November 16, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA), a rare cancer-focused innovative biotechnology company, reported that clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, will be presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) being held in Vienna, December 4 to 7, 2016 (Press release, Ariad, NOV 16, 2016, View Source;p=RssLanding&cat=news&id=2223132 [SID1234516644]).

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"We are excited that updated data from the ALTA trial on brigatinib in patients with ALK-positive non-small cell lung cancer will be presented at WCLC this year. We continue to be encouraged by the activity and safety profile seen in the ALTA trial, and especially the correlation between investigator and independent review assessments of response and response durability. ALTA data to be presented at the meeting will include approximately three months of additional follow-up as compared to the abstract," stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD.

The ALTA trial

The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy.

The primary endpoint of the ALTA trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include progression-free survival (PFS), confirmed ORR assessed by an independent review committee (IRC), CNS response and PFS, duration of response, safety and tolerability.

Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK+ NSCLC. The FDA has accepted brigatinib’s New Drug Application and has granted ARIAD’s request for Priority Review and set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD intends to submit a Marketing Authorization Application (MAA) for brigatinib to the European Medicines Agency (EMA) in early 2017.

Abstract Highlights on ALTA Trial Update
Data as of February 29, 2016 with Independent Review Committee (IRC) Data as of May 16, 2016

Accepted as a poster presentation, this abstract reports updated clinical data from the ALTA trial. A total of 222 patients with ALK+ NSCLC treated with prior crizotinib therapy were randomized in the study (110 patients in Arm B at the 180 mg dose level with a seven-day lead-in at 90 mg and 112 patients in Arm A at the 90 mg dose level). The last patient was enrolled in the study in September 2015.
The median follow-up was 8.3 months in Arm B and 7.8 months in Arm A.
Investigator-assessed confirmed ORR in Arm B was 54 percent. IRC-assessed confirmed ORR in Arm B was 53 percent. Investigator-assessed confirmed ORR in Arm A was 45 percent. IRC- assessed confirmed ORR in Arm A was 48 percent.
Investigator-assessed median PFS was 12.9 months and 9.2 months in Arm B and Arm A, respectively.
IRC-assessed median PFS was 15.6 months and 9.2 months in Arm B and Arm A, respectively.
The most common treatment-emergent adverse events (AEs), grade 3 or higher, (Arm B/A) were (excluding neoplasm progression): hypertension (6%/6%), increased creatine phosphokinase (CPK) (9%/3%), pneumonia (5%/3%), and increased lipase (3%/4%).
A subset of pulmonary AEs with early onset occurred in six percent of all patients (in 3% of patients, events were grade 3 or higher); no such events occurred after dose escalation to 180 mg QD in Arm B.
Abstract Highlights from Update on Clinical Data from Patients with Baseline CNS Metastases from Phase 1/2 and ALTA Trials
Data as of February 29, 2016 in ALTA Trial, and November 16, 2015 in Phase 1/2 Trial

Accepted as an oral presentation, this abstract reports clinical data from the Phase 1/2 and ALTA trials of brigatinib in patients with ALK+ NSCLC who had brain metastases at baseline.
In the Phase 1/2 trial, patients with advanced malignancies, including ALK+ NSCLC, received 30-300 mg of brigatinib per day. Efficacy in both trials and safety in ALTA are reported for patients with intracranial CNS metastases at baseline.
In the Phase 1/2 trial of brigatinib, 50/79 (63%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. In the ALTA trial, 153/222 (69%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. The efficacy analysis of Phase 1/2 trial data was based on an evaluable population (patients with at least one on-study brain scan, n=46), and the analysis of ALTA trial data was based on the intention-to-treat (ITT) population (n=153).
For patients with measurable brain lesions, the confirmed intracranial objective response rate was 53 percent (8/15) in the Phase 1/2 trial, and confirmed intracranial objective response rates were 67 percent (12/18) in Arm B and 42 percent (11/26) in Arm A in the ALTA trial.
There were 31 patients in the Phase 1/2 trial with only non-measurable lesions, and of these, 35 percent had complete resolution of lesions. In ALTA, there were 55 patients in Arm B and 54 in Arm A with only non-measurable lesions; of these, 18 percent and seven percent of patients, respectively, had complete resolution of lesions.
For patients with brain metastases at baseline, median intracranial PFS was 15.6 months in the Phase 1/2 trial (n=46); and 12.8 months (95% confidence interval [CI] 11.0 – not reached) and 15.6 months (95% CI 7.3-15.7 months) in ALTA Arm B and Arm A, respectively (n=73/ n=80).
In the ALTA trial, the most common treatment-emergent AEs, grade 3 or higher (excluding neoplasm progression), in patients with baseline brain metastases were (n=151 treated; Arm B/A): increased CPK (11%/1%), hypertension (7%/4%), increased lipase (3%/3%), and pneumonia (4%/1%).
For both presentations, ALTA data to be presented at the conference in Vienna will be based on an updated analysis, with a data cutoff date of May 31, 2016. These updated data will be included in the MAA application.

The schedule and meeting location for the sessions at WCLC, together with the abstract information and ARIAD’s investor event and NSCLC symposium, are listed below (all times are Central European Time Zone):

Brigatinib Oral Presentation

Title:
Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials
Abstract No/ID: 4374; Oral ID: OA08.06
Presenter: Scott Gettinger, M.D. (Yale Cancer Center)
Oral Session: Targeted Therapies in Brain Metastases
Session Date & Time: Monday, December 5, 2016, 16:00 – 17:30
Presentation Time: 11:57 a.m. to 12:09 p.m.
Location: Schubert 1

Brigatinib Posters

Title:
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial

Abstract No/ID: 4046; Poster ID: P3.02a-013
Presenter: D. Ross Camidge, M.D., Ph.D. (Colorado University Cancer Center)
Poster Session: PS03
Date & Time: Wednesday, December 7, 2016, 14:30 – 15:45
Location:
Hall B, poster area

Title:
Indirect Naive Comparison of Post-Crizotinib Treatments for ALK+ Non–Small Cell Lung Cancer (NSCLC)
Abstract No/ID: 4459; Poster ID: P3.02a-017
Presenter: Karen L. Reckamp, M.D. (City of Hope)
Poster Session: PS03
Date & Time: Wednesday, December 7, 2016, 14:30 – 15:45
Location: Hall B, poster area

AP32788 Poster

Title:
A Phase 1/2 Trial of the Oral EGFR/HER2 Inhibitor AP32788 in Non–Small Cell Lung Cancer (NSCLC)
Abstract No/ID: 5047; Poster ID: P2.06-007
Presenter: Robert C. Doebele, M.D., Ph.D. (University of Colorado)
Poster Session: PS02
Date & Time: Tuesday, December 6, 2016, 14:30 – 15:45
Location: Hall B, poster area

Investor and Analyst Briefing and Webcast

A webcast briefing will be held to review the updated brigatinib clinical data from the WCLC. Details will be provided at a later date.

NSCLC Global Symposium at WCLC

ARIAD will host a symposium titled, "Current and emerging treatments for patients with ALK+ NSCLC," that is open to all registered WCLC attendees. This symposium will be co-hosted by D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado and Professor Christoph Zielinski, M.D., Ph.D., chairman of the Clinical Division of Oncology, Medical University Vienna, Austria. They will be joined by Pasi A. Jänne, M.D., Ph.D., professor of medicine at the Dana Farber Cancer Institute, Boston, MA, USA, to review ALK inhibitor sequencing, the role of mutation testing, and current and future potential ALK inhibitors.

Date: Sunday, December 4, 2016
Time: 12:00 to 13:30 p.m. (CET)
Location: Strauss 3, Messe Wien Exhibition & Congress Center, Vienna
Congress:
17th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (www.IASLC.org)