On April 25, 2018 Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, www.provectusbio.com), ("Provectus" or the "Company"), a clinical-stage biotechnology company developing PV-10 as the first small molecule oncolytic immunotherapy for solid tumor cancers, and the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium ("POETIC"), a group of North American academic medical centers developing new pediatric cancer therapies, reported that preclinical data from ongoing pediatric cancer research into PV-10 will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting held in Chicago, IL from June 1-5, 2018 (Press release, Provectus Pharmaceuticals, APR 25, 2018, View Source [SID1234525706]). The presentation is entitled "In vitro and xenograft anti-tumor activity, target modulation and drug synergy studies of PV-10 against refractory pediatric solid tumors."

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The session title is Pediatric Oncology (Saturday, June 2, 8:00-11:30 AM), the topic is Pediatric Solid Tumors, the poster board number is 230, and the abstract number is 10557.

The preclinical pediatric cancer research was led by Aru Narendran, MD, PhD and researchers at the POETIC Laboratory for Pre-Clinical and Drug Discovery Studies at the University of Calgary (Canada), together with Tanya Trippett, MD, Director of POETIC, and researchers at Memorial Sloan Kettering Cancer Center. Further details regarding the presentation will be announced closer to the ASCO (Free ASCO Whitepaper) conference.

About PV-10

Provectus’ lead investigational cancer drug product, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

About the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium

The Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) was founded in February 2003 by Dr. Tanya Trippett at Memorial Sloan Kettering Cancer Center and Dr. Lia Gore at the University of Colorado Cancer Center. POETIC is composed of ten large academic medical centers in North America with a major emphasis on comprehensive cancer care and research that provide the collaborative and research strength needed to complete intensive phase I and II studies. Each of the institutions is uniquely suited to complete early studies in the pediatric and adolescent populations. POETIC’s assets include membership in NCI-designated Comprehensive Cancer Centers, on-site NIH-funded pediatric and/or general clinical translational research centers (CTRCs/CTSAs), and active collaborations with developmental therapeutics programs for adults at a majority of its member institutions. The availability of strong basic science and translational research programs at the institutions allows focus on the development and evaluation of new therapeutic strategies for patients with cancer and related disorders. POETIC’s pediatric oncology studies focus on the biologic basis for anti-cancer therapy, and in particular, attempt to explore and evaluate novel agents and/or combinations of therapies early in clinical development as well as new approaches to targeted delivery. For additional information about POETIC, please visit the Consortium’s website at www.poeticphase1.org.

On April 25, 2018 Asterias Biotherapeutics, Inc. (NYSE American:AST), a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with demyelination and cellular immunotherapies to treat cancer, reported that Cancer Research UK has released the first cGMP (current Good Manufacturing Practice) clinical grade lot of AST-VAC2 to be used to dose subjects enrolling into the first clinical study evaluating AST-VAC2 in non-small cell lung cancer (Press release, Asterias Biotherapeutics, APR 25, 2018, View Source;date=April+25%2C+2018&title=Asterias+Announces+Clinical+Grade+Lot+Released+to+Support+Dosing+of+First+Subjects+in+First+Clinical+Study+of+AST-VAC2 [SID1234525669]).

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"With the release of the first clinical grade lot of AST-VAC2 the first-in-human clinical trial of AST-VAC2 is expected to be initiated soon," stated Mr. Michael Mulroy, President and Chief Executive Officer. "With its potential as a ready-to-administer, off-the-shelf cancer immunotherapy, AST-VAC2 represents an exciting opportunity for Asterias to be more fully recognized as a participant in the rapidly evolving immuno-oncology sector."

Investigational therapies intended for human clinical applications must be manufactured in accordance with cGMP standards designed to help assure the safety and potency of drug products. To achieve cGMP standards, a product must be manufactured and released according to rigorous systems designed to ensure appropriate control of manufacturing facilities, equipment, raw materials, processes and testing procedures. Under the company’s agreement with Cancer Research UK, Asterias has transferred its innovative laboratory scale AST-VAC2 manufacturing process to Cancer Research UK’s Biotherapeutics Development Unit, which has developed, optimized and validated the process for cGMP manufacture and is responsible for producing cGMP AST-VAC2 for use in the upcoming Phase 1 clinical study in non-small cell lung cancer.

With the release of the clinical lot of AST-VAC2, the Company anticipates three sites opening for this study shortly and the first subjects to be dosed in the first half of 2018. As currently designed, the study will enroll up to 24 subjects into one of two cohorts, depending on the stage of each subject’s non-small cell lung cancer.

AST-VAC2 is a "first-in-class" allogeneic cancer immunotherapy that is composed of mature dendritic cells which are designed to kill tumor cells by stimulating immune responses to telomerase, a tumor antigen expressed by over 85% of malignant tumor cells. AST-VAC2 is intended to be available for "on demand" patient use because it is produced from allogeneic pluripotent stem cells that can be manufactured in scale and then cryopreserved.

AST-VAC2 is a platform cancer immunotherapy that could be investigated as a potential therapeutic for many cancer indications and for targeting of many antigens. The results from the Phase 1 clinical trial sponsored by Cancer Research UK could be used to support advanced clinical studies in one or more of the following areas:

Non-small cell lung cancer
Other indications showing high levels of telomerase activity and susceptibility to immunotherapy
In combination with check point or immune pathway inhibitors
In combination with additional antigens, including those arising from the exciting new field of tumor neoantigens
About AST-VAC2

AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program which provided proof-of-concept data, the AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase and, through this mechanism, target tumor cells. AST-VAC2 is based on a specific mode of action that is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.

About Non-Small Cell Lung Cancer and the AST-VAC2 Trial

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

As currently designed, the AST-VAC2 Phase 1 clinical trial will enroll up to twenty-four subjects into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate AST-VAC2 in up to 12 subjects with advanced non-small cell lung cancer. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase and overall clinical survival. These survival results will be compared directly to a control group who meet all of the other inclusion/exclusion criteria but do not possess the HLA-A2 gene. Assuming safety is demonstrated in the first cohort, enrollment will advance to a second cohort. In the second cohort, early stage subjects who have had successful resection of their tumor with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. These survival results will again be compared directly to a control group who meet all of the inclusion/exclusion criteria of cohort 2 but are not HLA-A2+. Subjects will be followed for one year for immune response to telomerase and for 2 years for the survival endpoints. Asterias and Cancer Research UK are exploring the combination of AST-VAC2 with an immune pathway inhibitor.

Late Tuesday, after a fifth buyout offer from Takeda, Shire said the Japanese drugmaker had finally landed on a proposal worth recommending to shareholders (Press release, Shire, APR 25, 2018, http://www.fiercepharma.com/pharma/shire-takeda-agree-to-preliminary-deal-and-analysts-agree-other-bidders-aren-t-coming?utm_source=internal&utm_medium=rss [SID1234525690]). It’s a cash-and-stock bid now worth $64 billion or so, about $4 billion more than its first offer.

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The deal still has to be approved by both boards and is subject to due diligence. The U.K.’s takeover board, which has strict rules for the timing and disclosure of bids, extended a deadline to give Takeda and Shire until May 8 to wrap it up.

In per-share terms, Takeda would fork over 0.839 new Takeda shares and $30.33 in cash for each Shire share. Based on Takeda’s share price at Monday’s close, that’s £49 per share, Shire said in a statement—and £5 per share more than its first bid.

That share price is a moving target, though; Takeda’s stock plummeted by 7% on the news Wednesday morning.

Structured this way, the deal "seems to be much more of a merger," Bernstein analyst Ronny Gal pointed out in a note to clients. Shire shareholders will receive 50% of the value of the combined company, and the companies will do reciprocal due diligence before any deal closes.

RELATED: Fifth and final bid? A determined Takeda said to be nearing $60B-plus Shire deal

At least one analyst isn’t so sure Shire shareholders will be interested.

"Are SHPG shareholders willing to accept an offer that is in effect 44% cash and 56% equity?" Jefferies’ David Steinberg wrote in a note to clients. While the latest bid is much more heavily weighted toward cash than Takeda’s third bid—just 38% cash—"we still wonder if it is enough to satisfy SHPG shareholders, who would still bear some not insignificant risk going forward as ~50% owners of NewCo," he wrote.

Gal, on the other hand, figures the deal will go through.

"The risk to the deal is unlikely in our view to come from Shire shareholders or anti-trust authorities," he wrote, noting that its Takeda’s shareholders, not Shire’s., that have sent the stock downward throughout the bidding process. Still, he pegged the probability of the deal going through at between 80% and 90%.

"Short of Takeda stock price imploding a deal is likely," he added.

RELATED: What would a Shire buy look like for Pfizer, Amgen or AbbVie? Analysts lay out pros and cons

Both analysts agree on one thing, though: Another bidder, which some industry watchers previously expected, probably won’t come out of the woodwork at this point.

"We expect Shire bankers to have left no stone unturned looking for other bidders," Gal wrote, with Steinberg adding that "we continue to think any potential group of buyers to be very limited … it’s arguably less than a 50% chance that another suitor emerges

On April 25, 2018 Immune Design (Nasdaq:IMDZ), an immunotherapy company focused on next-generation therapies in oncology, reported that it will report first quarter 2018 financial results after the close of U.S. financial markets on Wednesday, May 2, 2018 (Press release, Immune Design, APR 25, 2018, View Source [SID1234525707]). Immune Design management will host a webcast conference call at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time on May 2, 2018 to discuss the financial results and provide a corporate update.

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The live call may be accessed by dialing 844-266-9538 for domestic callers and 216-562-0391 for international callers. A live webcast of the call will be available online from the investor relations section of the company website at View Source and will be archived there for 30 days. A telephone replay of the call will be available for five days by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference code: 1088768.

On April 24, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported high-level results from the Phase III ARCTIC trial in patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least two prior treatments (Press release, AstraZeneca, APR 24, 2018, View Source [SID1234525609]). This randomised, open-label, multi-centre trial assessed the efficacy and safety of the combination of Imfinzi (durvalumab) plus tremelimumab, as well as Imfinzi and tremelimumab monotherapies, versus standard-of-care chemotherapy (SoC) in patients with PDL1-low/negative NSCLC (sub-study B), and Imfinzi monotherapy versus SoC in patients with PDL1-high NSCLC (sub-study A).

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In sub-study B, the combination of Imfinzi plus tremelimumab in patients with PD-L1 low/negative NSCLC did not meet the primary endpoints of a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) and overall survival (OS) compared to SoC. Activity and safety of monotherapy arms of sub-study B were consistent with prior published data.

Sub-study A was not powered for statistical significance; however, Imfinzi monotherapy showed a clinically-meaningful reduction in the risk of death compared to chemotherapy.

Full data from the ARCTIC trial will be presented at a forthcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "While we are disappointed that the combination of Imfinzi plus tremelimumab did not result in a statistically-significant survival benefit in this heavily pre-treated patient population, we are encouraged by the activity of Imfinzi monotherapy observed in this trial and look forward to presenting the full data from the ARCTIC trial at an upcoming medical meeting."

AstraZeneca recently received approval from the US FDA for Imfinzi for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

NOTES TO EDITORS
About ARCTIC

The ARCTIC trial was a randomised, open-label, multi-centre, global Phase III trial containing two sub-studies: sub-study A (1:1 randomisation of patients with PDL1-high tumours to Imfinzi (durvalumab) vs. SoC) and sub-study B (2:3:1:2 randomisation of patients with PDL1-low/negative tumours to Imfinzi monotherapy, Imfinzi plus tremelimumab or tremelimumab vs SoC). Tumour PD-L1 expression was assessed with the Ventana PD-L1 (SP263) assay with PD-L1 high defined as ≥25% of tumour cells with membrane staining.

About Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In February 2018, Imfinzi received US FDA approval for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Imfinzi also received accelerated approval in the US for the treatment of patients with locally-advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody and potential new medicine, as a first-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

About tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicines that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being tested in an extensive clinical-trial programme in combination with Imfinzi in NSCLC, locally-advanced or metastatic urothelial carcinoma, head and neck cancer, liver cancer and blood cancers.