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Alkermes to Present Preclinical Data on ALKS 4230 at the American Association for Cancer Research Annual Meeting

On March 27, 2017 Alkermes plc (NASDAQ: ALKS) reported that preclinical data on the company’s immuno-oncology drug candidate, ALKS 4230, an engineered fusion protein designed for selective activation of the interleukin-2 (IL-2) receptor, will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held from April 1-5, 2017 in Washington D.C (Press release, Alkermes, MAR 27, 2017, View Source [SID1234518272]). ALKS 4230 is designed to preferentially bind and signal through the intermediate affinity IL-2 receptor complex, thereby selectively activating and increasing the number of tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response.

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Details of the preclinical data poster presentations are as follows:

April 2, 2017, 1:00 – 5:00 p.m. ET – Abstract 591 (Poster): Efficacy of ALKS 4230, a novel immunotherapeutic agent, in murine syngeneic tumor models alone and in combination with immune checkpoint inhibitors.

In a murine lung tumor metastasis model, treatment with ALKS 4230 as a single agent resulted in greater anti-tumor efficacy relative to recombinant human IL-2 (rhIL-2) and was associated with selective expansion of memory CD8+ T cells and NK cells (tumor-killing cells), without expansion of regulatory T (Treg) cells. Specifically, ALKS 4230 treatment resulted in dose-dependent reduction of lung tumor colonization, with 100% inhibition at the highest dose tested. In contrast, the maximal level of inhibition achieved by rhIL-2 was 60-70% at multiple dose levels, demonstrating that increasing doses of rhIL-2 did not result in greater inhibition.
Combination regimens with ALKS 4230 and either anti-CTLA4 or anti-PD-1 checkpoint inhibitor therapies in murine tumor models resulted in durable anti-tumor immunotherapeutic effects and increased survival rates.
April 3, 2017, 1:00 – 5:00 p.m. ET – Abstract 2663 (Poster): Characterization of the pharmacodynamic immune response to a novel immunotherapeutic agent, ALKS 4230, in mice and non-human primates.

Data demonstrated that ALKS 4230 drove dose-dependent expansion of memory CD8+ T cells and NK cells in mice, and total CD8+ T cells and NK cells in non-human primates, without activation and minimal expansion of CD4+ Tregs in mice and non-human primates. These pharmacodynamics effects persisted for several days after ALKS 4230 was cleared from circulation.
In addition to these preclinical data presentations, a poster outlining the dose selection rationale for the ongoing phase 1 study of ALKS 4230 will be presented. The poster presentation details are as follows:

April 4, 2017, 1:00 – 5:00 p.m. ET – Abstract 4088 (Poster): First-in-human dose selection for ALKS 4230, an investigational immunotherapeutic agent.

The selection of the 0.1 µg/kg starting dose for the first-in-human study of ALKS 4230 was determined, based on the Minimal Anticipated Biological Effect Level (MABEL) approach.
For more information, including a complete list of abstracts, please visit the AACR (Free AACR Whitepaper) website at View Source

About ALKS 4230
ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects while overcoming limitations of existing IL-2 therapy, which activates both immunosuppressive and tumor-killing immune cells.

Advaxis Provides Phase 1 Data of Higher Dose Axalimogene Filolisbac

On March 27, 2017 Advaxis, Inc. (NASDAQ:ADXS), a biotechnology company developing cancer immunotherapies, reported that it has published online a poster previously presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool that showed axalimogene filolisbac achieved durable response in a patient with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC) (Press release, Advaxis, MAR 27, 2017, View Source [SID1234518271]).

Nine patients who had documented disease progression after they had received curative treatments of chemotherapy and/or radiation with or without bevacizumab were enrolled in this phase 1, open-label, dose-determining study. Axalimogene filolisbac was well-tolerated across two dose levels. The study also established a recommended phase 2 dose of 1×1010 CFU and demonstrated antitumor activity at that dose. Axalimogene filolisbac was safely administered at 5 and 10 times the dose levels previously studied, without any significant toxicity. One patient experienced an ongoing and durable partial response. This patient was recently featured in the Augusta Chronicle, as she is being treated at the Georgia Cancer Center at Augusta University. Read the full Augusta Chronicle article here.

"The best overall tumor response in eight of the nine enrolled patients is encouraging in evaluating the potential of axalimogene filolisbac," said Sharad Ghamande, principal investigator and Professor and Director of Gynecologic Oncology at the Georgia Cancer Center at Augusta University. "We were pleased to see a sustained and durable partial response in one patient, which is very rare for this kind of tumor that is unresponsive to chemotherapy, and survival in these patients is often less than 10 months. In addition, we could safely administer the drug at 5 and 10 times the dose levels previously studied, without any significant toxicity."

There was only one instance of dose-limiting toxicity, with that patient experiencing a grade 3 treatment related adverse event (TRAE) of hypotension at a dose of 5×109 CFU. Across all doses, eight of nine patients experienced a grade 1-2 TRAE, including chills, nausea and hypotension.

The poster on the phase 1 data, "High-dose treatment with ADXS11-001, a Listeria monocytogenes-listeriolysin O (Lm-LLO) immunotherapy, in women with cervical cancer: a phase I, dose-escalation study" (no. 58) is available at www.advaxis.com. The company is preparing to initiate a phase 3 trial in PRmCC later this year.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.

Data from Phase 2 Study of Progenics’ PSMA-Targeted Imaging Agent 1404 Published in Journal of Nuclear Medicine

On March 24, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported the publication of previously-reported results from the Phase 2 study of 1404 in the online edition of the Journal of Nuclear Medicine (Press release, Progenics Pharmaceuticals, MAR 24, 2017, View Source [SID1234518266]). 1404 is a PSMA-targeted small molecule SPECT/CT imaging agent that is designed to visualize prostate cancer.

“The results from this study highlight the potential for 1404 to better assess the stage and extent of a patient’s prostate cancer versus biopsy,” stated Professor Karolien Goffin, M.D., Ph.D., University Hospitals Leuven, author of the publication. “Importantly, 1404 may be used as a surrogate marker for Gleason Score, and could be used to evaluate lymph node involvement in patients with intermediate and high risk prostate cancer, which signals disease that has spread beyond the prostate. The data provide a strong rationale for continued development of 1404.”

Progenics is currently evaluating 1404 in a Phase 3 study. The study is enrolling patients with newly diagnosed low grade prostate cancer, whose biopsy indicates a histopathologic Gleason grade of ≤ 3+4 severity and/or are candidates for active surveillance. The study is designed to evaluate the specificity of 1404 imaging to identify patients without clinically significant prostate cancer and sensitivity to identify patients with clinically significant disease.

About 1404, an Imaging Compound Targeting Prostate Specific Membrane Antigen

Progenics’ molecular imaging radiopharmaceutical product candidate 1404 targets the extracellular domain of prostate specific membrane antigen (PSMA), a protein amplified on the surface of > 95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. 1404 is labeled with Technetium-99m, a gamma-emitting isotope that is widely available, is easy to prepare, and is attractive for nuclear medicine imaging applications. The image created provides the opportunity to visualize cancer, potentially allowing for improved detection and staging, more precise biopsies, and a targeted treatment plan including active surveillance as a disease management tool.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 161,360 new cases of prostate cancer will be diagnosed and about 26,730 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors.

Data from Phase 2 Study of Progenics’ PSMA-Targeted Imaging Agent 1404 Published in Journal of Nuclear Medicine

The data published today reviews previously reported data demonstrating the sensitivity of 1404 to detect prostate cancer using both visual and semi-quantitative tumor to background (TBR) scores. The uptake within the prostate gland evaluated by both visual and TBR scores correlated significantly with Gleason Score.

"The results from this study highlight the potential for 1404 to better assess the stage and extent of a patient’s prostate cancer versus biopsy," stated Professor Karolien Goffin, M.D., Ph.D., University Hospitals Leuven, author of the publication. "Importantly, 1404 may be used as a surrogate marker for Gleason Score, and could be used to evaluate lymph node involvement in patients with intermediate and high risk prostate cancer, which signals disease that has spread beyond the prostate. The data provide a strong rationale for continued development of 1404."

Progenics is currently evaluating 1404 in a Phase 3 study. The study is enrolling patients with newly diagnosed low grade prostate cancer, whose biopsy indicates a histopathologic Gleason grade of ≤ 3+4 severity and/or are candidates for active surveillance. The study is designed to evaluate the specificity of 1404 imaging to identify patients without clinically significant prostate cancer and sensitivity to identify patients with clinically significant disease.

About 1404, an Imaging Compound Targeting Prostate Specific Membrane Antigen

Progenics’ molecular imaging radiopharmaceutical product candidate 1404 targets the extracellular domain of prostate specific membrane antigen (PSMA), a protein amplified on the surface of > 95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. 1404 is labeled with Technetium-99m, a gamma-emitting isotope that is widely available, is easy to prepare, and is attractive for nuclear medicine imaging applications. The image created provides the opportunity to visualize cancer, potentially allowing for improved detection and staging, more precise biopsies, and a targeted treatment plan including active surveillance as a disease management tool.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 161,360 new cases of prostate cancer will be diagnosed and about 26,730 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors.

Blue Earth Diagnostics receives positive CHMP opinion for Axumin™ (Fluciclovine (18F)) for PET imaging of recurrent prostate cancer

On March 24, 2017 Blue Earth Diagnostics, a molecular imaging diagnostics company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending that Axumin (fluciclovine (18F)) is granted marketing authorization in the European Union (Press release, Blue Earth Diagnostics, MAR 24, 2017, View Source [SID1234518269]). The recommendation is for Axumin use in Positron Emission Tomography (PET) imaging to detect recurrence of prostate cancer in adult men with a suspected recurrence based on elevated blood prostate specific antigen (PSA) levels after primary curative treatment. The CHMP’s positive opinion will now be reviewed by the European Commission. If approved, Axumin will be the first and only PET imaging agent indicated for use in men with suspected recurrent prostate cancer in all European Union member states as well as in Iceland, Liechtenstein and Norway.

Prostate cancer is the most common cancer in Europe for men, with around 343,000 new cases diagnosed each year1. While most primary prostate cancer can be successfully treated, the disease recurs in up to one-third of patients. In some patients, recurrent disease is detectable only by a rise in PSA levels, but often the location of the recurrence cannot consistently be located by conventional imaging, limiting treatment guidance. Axumin was developed to target the increased amino acid transport that occurs in many cancers, including prostate cancer. It is labelled with the radioisotope (18F), enabling it to be visualized in the body with PET imaging.

"The CHMP’s positive recommendation for Axumin is a major advance in Blue Earth’s commitment to providing a readily available PET imaging agent to detect and localize suspected biochemically recurrent prostate cancer for the thousands of men in Europe affected by this disease," said Dr. Jonathan Allis, CEO, Blue Earth Diagnostics. "Information provided by an Axumin PET scan can help physicians localize disease, which may assist treatment decisions. We now look forward to working with our commercial manufacturing and distribution associates to be ready to make Axumin widely available to doctors and their patients across Europe."

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ABOUT AXUMINTM (FLUCICLOVINE (18F))

Axumin (fluciclovine (18F)) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues, and is labelled with the radioisotope (18F) for PET imaging. Fluciclovine (18F) was invented at Emory University in Atlanta, Ga., USA, with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications, such as glioma.

ABOUT POSITRON EMISSION TOMOGRAPHY (PET) IMAGING

Positron emission tomography (PET) is an imaging test that uses a special type of scanner in conjunction with a radiolabeled tracer (a molecular imaging agent) to visually examine biochemical processes in the body. PET scan images depict biological function and are complementary with technologies which show anatomical information, such as computed tomography (CT) scans or magnetic resonance imaging (MRI).