On May 20, 2021 Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) reported that the BioNTech Europe GmbH has entered into an agreement with Turkey’s Ministry of Health to supply 60 million additional doses of the companies’ COVID-19 vaccine, with an option for an additional 30 million doses. On December 25, 2020, the two companies announced an initial agreement to provide 30 million doses of the Pfizer-BioNTech vaccine to Turkey (Press release, BioNTech, MAY 20, 2021, View Source [SID1234580352]). This second supply agreement brings the total number of doses to be supplied to Turkey to up to 120 million, all of which will be delivered in 2021.

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"Our goal is to deliver as many doses of our COVID-19 vaccine as possible to people around the world to help end this pandemic, reduce COVID-19-related hospitalisations and return to a normal life. We are grateful to be able to make an important contribution to Turkey’s vaccination efforts and for the trust placed in us," said Ugur Sahin, M.D., CEO and Co-founder of BioNTech.

"We are hopeful that this agreement will further boost Turkey’s COVID-19 vaccination drive. Pfizer is committed to contributing to public health in Turkey and very proud to have a global partner such as BioNTech in the global fight against the pandemic," said M. Cem Açık, Pfizer Country Manager Turkey.

The vaccine, which is based on BioNTech’s proprietary mRNA technology, was developed by both BioNTech and Pfizer. BioNTech is the Marketing Authorization Holder in the European Union, and the holder of emergency use authorizations or equivalent in the United States (jointly with Pfizer), United Kingdom, Canada and other countries in advance of a planned application for full marketing authorizations in these countries.

AUTHORIZED USE IN THE U.S.:
The Pfizer-BioNTech COVID-19 vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.

IMPORTANT SAFETY INFORMATION FROM U.S. FDA EMERGENCY USE AUTHORIZATION PRESCRIBING INFORMATION:

Do not administer Pfizer-BioNTech COVID-19 vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 vaccine
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer-BioNTech COVID-19 vaccine
Monitor Pfizer-BioNTech COVID-19 vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention guidelines (View Source)
Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 vaccine
The Pfizer-BioNTech COVID-19 vaccine may not protect all vaccine recipients
In clinical studies, adverse reactions in participants 16 years of age and older included pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%), injection site swelling (10.5%), injection site redness (9.5%), nausea (1.1%), malaise (0.5%), and lymphadenopathy (0.3%)
In a clinical study, adverse reactions in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%)
Severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions, diarrhea, vomiting, and pain in extremity (arm) have been reported following administration of the Pfizer-BioNTech COVID-19 vaccine outside of clinical trials. Additional adverse reactions, some of which may be serious, may become apparent with more widespread use of the Pfizer-BioNTech COVID-19 vaccine
Available data on Pfizer-BioNTech COVID-19 vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy
Data are not available to assess the effects of Pfizer-BioNTech COVID-19 vaccine on the breastfed infant or on milk production/excretion
There are no data available on the interchangeability of the Pfizer-BioNTech COVID-19 vaccine with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of Pfizer-BioNTech COVID-19 vaccine should receive a second dose of Pfizer-BioNTech COVID-19 vaccine to complete the vaccination series
Vaccination providers must report Adverse Events in accordance with the Fact Sheet to VAERS online at View Source For further assistance with reporting to VAERS call 1-800-822-7967. The reports should include the words "Pfizer-BioNTech COVID-19 Vaccine EUA" in the description section of the report
Vaccination providers should review the Fact Sheet for Information to Provide to Vaccine Recipients/Caregivers and Mandatory Requirements for Pfizer-BioNTech COVID-19 vaccine Administration Under Emergency Use Authorization
Please see Emergency Use Authorization (EUA) Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers) including Full EUA Prescribing Information available at www.cvdvaccine-us.com.

On May 20, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported clinical and biomarker data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (Press release, Oncolytics Biotech, MAY 20, 2021, View Source [SID1234580368]). The data will be featured in an upcoming electronic poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is taking place virtually from June 4 – 8, 2021.

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The newly announced data are from a phase 2 trial evaluating pelareorep in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in pancreatic adenocarcinoma patients who progressed after first-line treatment. Findings from the trial indicate that pelareorep and pembrolizumab synergize and show anti-cancer activity in these difficult-to-treat patients, which is mediated through the complementary immunotherapeutic effects of the two agents.

"These results are very promising, particularly considering the extremely challenging patient population enrolled in the trial. That we saw a response signal in select patients, despite the absence of chemotherapy, provides evidence of the considerable anti-cancer activity of pelareorep-pembrolizumab combination therapy," said Principal Investigator, Devalingam Mahalingam, M.D., Ph.D., Associate Professor of Medicine at The Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "We notably observed an association between treatment-induced anti-cancer immune responses and improved tumor control in some patients, which demonstrates pelareorep’s underlying immunologic mechanism of action and validates the strategy of combining it with checkpoint inhibition. I look forward to discussing these data with the scientific community at the upcoming ASCO (Free ASCO Whitepaper) conference and to the continued evaluation of pelareorep-checkpoint inhibitor combination therapy in select patients with pancreatic and other gastrointestinal cancers."

The data presented in the upcoming ASCO (Free ASCO Whitepaper) poster represent an update based on additional data that was collected after the cutoff date used for the poster’s corresponding abstract. Key data and conclusions that will be featured in this upcoming poster include:

Disease control was achieved in 42% (5/12) of patients, with one patient achieving a partial response and four patients achieving stable disease
On-treatment tumor biopsies showed pelareorep replication and increased infiltration of CD8+ T cells and PD-L1+ cells relative to pre-treatment samples
Patients achieving disease control showed reductions in pro-tumor regulatory T (T­reg) cells in the peripheral blood and tumor tissue compared to those with progressive disease
Patients achieving disease control showed increased activation of anti-cancer CD8+ T cells in the peripheral blood compared to those with progressive disease
Pelareorep-pembrolizumab combination therapy was found to be well tolerated, with most treatment-related adverse events being grade 1 or 2
Bin Zhang, M.D., Ph.D., Professor at The Northwestern University Feinberg School of Medicine, commented, "These data show that pelareorep can train the immune system to target pancreatic cancer while simultaneously promoting the infiltration of T cells into the tumor and remodeling the tumor microenvironments (TMEs) to be less immunosuppressive. This positions pelareorep to synergistically combine with both checkpoint inhibitors as well as a broad range of other immuno-oncology agents."

"The findings from this study highlight the broad applicability of pelareorep’s immunotherapeutic mechanism of action as they are consistent with what has been seen in clinical trials in other indications such as breast cancer," added Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics. "The compelling findings from this phase 2 study highlight the potential of pelareorep to address the critical unmet need in pancreatic cancer by reversing the immunosuppressive TMEs that often limit the efficacy of checkpoint inhibitors. The anti-cancer activity demonstrated in this study bodes well for a successful outcome in our GOBLET trial, which includes a cohort evaluating pelareorep and the PD-L1 inhibitor atezolizumab in combination with chemotherapy as first-line therapy in metastatic pancreatic cancer patients."

The electronic poster, titled, "Treatment with pembrolizumab in combination with the oncolytic virus pelareorep promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma" will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at 9:00 a.m. ET on June 4, 2021. A copy of the poster will also be posted on the Posters & Publications page of Oncolytics’ website (LINK).

Oncolytics plans to further develop pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer in collaboration with Roche and AIO-Studien-gGmbH (AIO) through the GOBLET study, a phase 1/2 multi-center trial designed to investigate the use of pelareorep in combination with Roche’s anti-PD-L1 inhibitor atezolizumab (Tecentriq) in patients with metastatic pancreatic, metastatic colorectal and advanced anal cancers (link to the GOBLET announcement PR). Oncolytics expects the first patient to be dosed in GOBLET in mid-2021.

About GOBLET

The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic GI tumors. The study will be conducted at 25 centers in Germany. The primary endpoint of the study is safety, with overall response rate and biomarker evaluation (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned for enrollment across four separate cohorts:

Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 2nd and 3rd line metastatic colorectal cancer patients that are diagnosed as MSI (microsatellite instability) high (n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).
About Gastrointestinal Cancer

Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,610 new cases of colon cancer and 43,340 new cases of rectal cancer diagnosed in the U.S. in 20201. Also, for the 2020 year, the American Cancer Society estimates there will be 57,600 new cases of pancreatic cancer2 and 8,590 new cases of anal cancer 3 in the U.S.

On May 20, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the presentation of data from preclinical studies of XTX202, its tumor-selective interleukin-2 (IL-2) product candidate, demonstrating selective anti-tumor activity and favorable tolerability with no systemic toxicity observed (Press release, Xilio Therapeutics, MAY 20, 2021, View Source [SID1234580385]). The data will be reported in a poster entitled "XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates" at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at the start of the meeting on June 4, 2021 at 9am ET.

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Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment (TME) and have the potential to result in localized, tumor-selective clinical activity without dose-limiting toxicities. XTX202, Xilio’s lead cytokine product candidate, is an engineered form of IL-2 that is masked with a protein domain to prevent binding activity until cleaved off by TME-associated proteases.

"The power of IL-2 to activate the immune system as a cancer therapeutic is promising, but utility of IL-2 agents has historically been greatly reduced due to toxicities," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "We have engineered XTX202 to overcome those challenges, with key features designed to ensure it is released and activated locally within the TME, where it selectively binds to IL-2 receptors on immune cells. We are excited to present these data which, for the first time, demonstrate selective tumor-inhibition and favorable tolerability of XTX202 in preclinical models. With these data, we plan to complete IND-enabling studies and submit an IND application in the second half of 2021 to evaluate XTX202 in patients with solid tumors."

Data reported in the poster are from preclinical studies in both mouse and non-human primate (NHP) models, including comparisons between XTX202 and XTX200, a non-masked, parent version of XTX202, as well as aldesleukin, a synthetic form of IL-2 approved for certain cancer indications by the U.S. Food and Drug Administration. Key data include:

XTX202, in its masked form, did not bind to IL-2 receptors, and matrix metalloproteinase (MMP) activation of XTX202 restored full binding to IL-2 receptor beta that is found on immune activating CD8 T cells and natural killer cells, illustrating the tight, protease-dependent control of IL-2 activity conferred by XTX202.
XTX202 was engineered to eliminate binding to IL-2Ra in order to enhance immune activation by CD8 T cells and NK cells, and to minimize immune suppression by regulatory T cells. No binding to IL-2Ra was detectable even after MMP-dependent activation of XTX202.
XTX202 inhibited tumor growth in syngeneic mouse models as a single agent with no evidence of toxicity or peripheral immune activation, thus demonstrating tumor selective activity.
XTX202 matched the tumor growth inhibition activity of aldesleukin and the non-masked control XTX200, without activation of immune response outside the TME, thereby avoiding the body weight loss in mice that was associated with doses of XTX200 or aldesleukin required for tumor growth inhibition.
XTX202 was well-tolerated in repeat dose studies in NHPs at doses up to 30 mg/kg.
XTX202 is estimated to have a greater than 100-fold improvement in therapeutic index compared to aldesleukin.

On May 20, 2021 Phosplatin Therapeutics Inc., a clinical stage pharmaceutical company focused on oncology therapeutics, reported additional data in a sub-population of heavily pre-treated, patients with metastatic castrate-resistant prostate cancer (mCRPC) from its Phase 1b study of PT-112, the company’s lead clinical agent, in combination with PD-L1 inhibitor avelumab (Press release, Phosplatin, MAY 20, 2021, View Source [SID1234580401]). The combination was generally well tolerated and demonstrated meaningful anti-tumor effects. The report from the study, entitled "A Phase 1b study of novel immunogenic cell death inducer PT-112 plus PD-L1 inhibitor avelumab in metastatic castrate-resistant prostate cancer (mCRPC) patients," by lead author Alan H. Bryce, MD et al., is currently available online, as part of the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, which is taking place virtually from June 4-8, 2021.

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"Such patients with late-stage prostate cancer have limited treatment options and are in need of new approaches to manage what is often aggressive disease," said Matthew R. Price, co-founder and Chief Operating Officer. "We are encouraged by the prospect of using PT-112 in combination with immune-checkpoint inhibition, based upon our Phase 1b data."

The PT-112-103-PAVE-1 study (NCT03409458) enrolled a total of 32 patients with mCRPC during dose-finding: 18 patients in the dose escalation phase, who received 150-200mg/m2 PT-112 on days 1, 8 and 15 of a 28-day cycle, and 14 patients in a supplemental cohort, who received 300 mg/m2 PT-112 on days 1 and 15. (Note: one patient received PT-112 on days 1 and 15 at 200mg/m2.) All patients received avelumab (800 mg) on days 1 and 15. Patients had exhausted available therapies, with a median 7 lines of prior treatment. Key findings included the following:

PT-112 treatment in combination with avelumab was generally well tolerated in this heavily pre-treated, advanced mCRPC patient population with no available life-prolonging therapeutic options
The combination provided meaningful antitumor effects, including decreases in tumor volume as well as reductions in prostate-specific antigen (PSA) and alkaline phosphatase (ALP) serum markers.
Antitumor effects included eight (25%) patients with a PSA reduction of ≥50% (PSA50), five (16%) of which were confirmed. Of 10 patients with RECIST-measurable disease, three had tumor volume reductions, one with a confirmed partial response (PR). Twenty-four (75%) patients showed a reduction in serum alkaline phosphatase (ALP). Reductions in ALP may be indicative of anti-cancer activity at bone sites of disease. Improvement in patient-reported pain was also observed.
At the higher dose level (300 mg/m2 PT-112, given every two weeks) 4 of 13 (31%) experienced PSA50 reduction, confirmed in 3 of 13 (23%) patients.
The PT-112-103-PAVE-1 study has completed the dose escalation phase, and a dose confirmation cohort in non-small cell lung cancer is currently enrolling.

Additionally, the Phase 2 PT-112 monotherapy trial (NCT02266745) is currently enrolling patients with late-stage mCRPC.

"The early results of our immunotherapy combination in this sub-population clearly indicate the potential of such a treatment paradigm for patients with metastatic castrate-resistant prostate cancer," said Joseph F. O’Donnell, MD, Chief Medical Officer at Phosplatin Therapeutics. "We continue our work to demonstrate the effects of PT-112’s immunogenic cell death (ICD) induction, including with immune-profiling analyses, and also believe its osteotropism lends further rationale to treat these patients, most of whom have bone metastatic involvement. We are grateful to our wonderful collaborators and are encouraged to continue further clinical development of PT-112 in patients with advanced prostate cancer with our ongoing Phase 2 monotherapy trial."

"A Phase 1b study of novel immunogenic cell death inducer PT-112 plus PD-L1 inhibitor avelumab in metastatic castrate-resistant prostate cancer (mCRPC) patients" is available for viewing in the ASCO (Free ASCO Whitepaper) Meeting Library at View Source

About PT-112

PT-112 is a novel small molecule conjugate of pyrophosphate that possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents the best-in-class small molecule inducer of this immunological form of cancer cell death and is currently under Phase 2 development. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) 2018 Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) is the third completed Phase 1 study of PT-112. Monotherapy phase 2 development is ongoing in mCRPC, and the anti-PD-L1 combination study is ongoing in a dose confirmation cohort of patients with non-small cell lung cancer (NSCLC).

On May 20, 2021 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported that the U.S. Food and Drug Administration (US FDA) has provided details of the additional information it is requesting regarding its Chimeric Antigen Receptor-T cell therapy (CAR-T) being developed in partnership with Moffitt Cancer Center (Press release, Anixa Biosciences, MAY 20, 2021, View Source [SID1234580336]).

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The Investigational New Drug (IND) application for this study was submitted in March, and the US FDA subsequently requested additional information before approving the trial. The details of that information request have now been provided by the FDA. Anixa and Moffitt feel that the requested information can be assembled and provided to the FDA within approximately 30 days, after which the FDA will again respond within 30 days after the submission.

This technology is an autologous cell therapy that requires the manufacture of a unique drug product for each individual patient. The therapeutic product is comprised of engineered T-cells that target the follicle stimulating hormone receptor (FSHR). FSHR is found at immunological levels exclusively on the granulosa cells of the ovaries. Since the target is a hormone receptor, this technology is also known as CER-T (Chimeric Endocrine Receptor T-cell) therapy, a new type of CAR-T.

Dr. Amit Kumar, President and CEO of Anixa Biosciences, stated, "We are pleased to receive this letter with the detailed information request. While we hope to comply with the request within 30 days, certain assays may require additional time for validation before submission. We will strive to file our submission as soon as possible and we will seek to initiate this clinical trial before the end of the year."