On June 23, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to BioNTech’s fully owned product candidate BNT211 for the third- or later-line treatment of testicular germ cell tumors (Press release, BioNTech, JUN 23, 2022, View Source [SID1234616204]). BNT211 is a potential first-in-class therapeutic approach which comprises a synergistic combination of two of the Company’s proprietary drug products, an autologous chimeric antigen receptor (CAR) T cell therapy targeting the oncofetal antigen Claudin-6 (CLDN6) and a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac). The product candidate is currently being investigated in an ongoing Phase 1/2 study (NCT04503278; 2019-004323-20) that aims to evaluate the safety and preliminary efficacy in heavily pretreated patients with relapsed or refractory advanced solid tumors.

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"Patients with relapsed or treatment refractory testicular cancers have a poor prognosis with limited remaining treatment options. The PRIME designation underlines the potential of our approach in this high medical need setting. Our approach brings together several new elements: Firstly, targeting CLDN6, a pan-cancer cell surface marker, secondly, our CAR design, and thirdly, "remote control" of CAR T cells by our uridine RNA-lipoplex based vaccine. We believe that a combination of engineered T cells and mRNA vaccines in one treatment regimen can stimulate and expand T cells. This could enable us to develop truly powerful precision immunotherapies," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "With the PRIME status and support by the EMA, we aim to expedite the further development of the BNT211 program to bring a novel therapeutic option for patients with life-threatening testicular cancer, and thus to extend the successes of CAR-T therapy also to hard-to-treat solid tumors."

The designation is based on positive preliminary Phase 1/2 data from the ongoing study that was presented at the AACR (Free AACR Whitepaper) Annual Meeting in April 2022. The results demonstrated that treatment with CLDN6 CAR-T alone or in combination with CARVac was well tolerated and showed encouraging signs of anti-tumor activity in testicular cancer patients at the first evaluated dose levels. In the study all six patients with heavily pretreated testicular cancer eligible for efficacy analysis showed clinical benefits highlighting the potential of this novel approach. One patient achieved a complete response 18 weeks after infusion. Three patients achieved a partial response and showed deepening and durability of responses (one of them in the lowest CAR-T dose level cohort in combination with CARVac). One patient had stable disease with shrinkage of target lesions.

The PRIME scheme is a regulatory mechanism introduced by the EMA that provides early and proactive support to developers of promising medicines, to optimize development plans and speed up evaluations so these medicines can reach patients faster. The goal is to help patients benefit as early as possible from innovative new therapies that have demonstrated the potential to significantly address an unmet medical need.

About BNT211
Aiming to harness the power of cell therapies for solid cancers and to overcoming hurdles to date, BioNTech has combined their CAR-T and FixVac platform technologies to develop a highly tumor-specific CAR-T cell therapy product which is consecutively enhanced by a CAR-T Cell Amplifying RNA Vaccine (CARVac) that is based on BioNTech`s mRNA-lipoplex technology and encodes for the respective CAR-T target antigen. The CARVac is based on BioNTech’s backbone-optimized uridine mRNA (uRNA)-lipoplex technology which through its inherent adjuvant function enables a potent T cell stimulation to improve persistence and functionality of the adoptively transferred CAR-T cells, thus enabling and maintaining a therapeutic effect even at low CAR-T doses. BNT211 is an investigational CAR-T cell therapy directed against the novel oncofetal antigen Claudin-6 (CLDN6), a target discovered by BioNTech founders and expressed on multiple solid tumors such as ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The program is currently being evaluated in a first-in-human Phase 1/2 trial as a monotherapy and in combination with a CLDN6-encoding CARVac, aiming to boost persistence and functionality of the CLDN6-CAR-T cells, in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

On June 23, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported that it has received approval from the U.S. Food and Drug Administration (FDA) for its ongoing potentially pivotal global study evaluating the efficacy and safety of Berubicin compared with Lomustine (Gleostine) administered after first line therapy for the treatment of recurrent glioblastoma multiforme (GBM), one of the most aggressive types of brain cancer (Press release, CNS Pharmaceuticals, JUN 23, 2022, https://www.prnewswire.com/news-releases/cns-pharmaceuticals-receives-approval-from-us-fda-for-protocol-amendment-to-ongoing-potentially-pivotal-global-trial-evaluating-berubicin-for-the-treatment-of-gbm-301573601.html [SID1234616220]).

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"We are pleased to have received this positive response from the FDA and to continue driving the Berubicin clinical development program forward. The key objectives for the protocol amendment are based on the feedback we received from investigators and further consideration of the needs of patients on the study. We have also incorporated the recent WHO classification of glioblastoma1 with pertinent guidelines, ensuring that these patients meet specific criteria that allows us to accurately position the program for success. I am proud of the progress we continue to make on the clinical and regulatory fronts and look forward to further advancing this important trial," commented John Climaco, CEO of CNS Pharmaceuticals.

Berubicin is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier currently being evaluated in a global potentially pivotal study evaluating its efficacy and safety.

The potentially pivotal trial is an adaptive, multicenter, open-label, randomized and controlled study in adult patients with recurrent glioblastoma multiforme (WHO Grade IV) after failure of standard first-line therapy. The primary endpoint of the study is Overall Survival (OS), which is a rigorous endpoint that the FDA has recognized as a basis for approval of oncology drugs when a statistically significant improvement can be shown relative to a randomized control arm. Results from the trial will compare Berubicin to a current standard of care (Lomustine), with a 2 to 1 randomization of patients to receive either Berubicin or Lomustine. The amended protocol expands eligibility for the study to patients who have received additional treatments as part of the first line therapy for their disease considering advancements in this area. This change was made due to the complexity of new agents introduced as a component of first line therapy, which allows an additional group of patients that can enroll on the study after what may constitute multiple procedures as their initial treatment.

A pre-planned, non-binding futility analysis will be performed after 30 to 50% of all planned patients have completed 6 months on therapy. This evaluation will include safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.

"The operational objectives of this study remain our priority, including using patient reported outcomes, stratification based on MGMT methylation status (a prognostic factor in glioblastomas), and providing both the study drug, Berubicin, as well as the comparator drug, Lomustine, to all sites. With the recent regulatory authority approvals received in Europe, we are currently on the cusp of opening clinical sites globally, including France, Italy, Spain, and Switzerland, to expand the scope and outreach to patients for this trial. We remain dedicated to driving this study forward and ultimately hope to provide a much-needed option for treatment in GBM as a safe and effective therapy," added Sandra L. Silberman, M.D., Ph.D. Chief Medical Officer of CNS Pharmaceuticals.

The FDA has granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with them to provide guidance on expediting the development and review process. Additionally, the Company has also received Orphan Drug Designation from the FDA which may provide seven years of marketing exclusivity upon approval of an NDA.

For more information about the potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

About Berubicin
Berubicin is an anthracycline, a class of anticancer agents that are among the most powerful chemotherapy drugs and effective against more types of cancer than any other class of chemotherapeutic agents. Anthracyclines are designed to utilize natural processes to induce deoxyribonucleic acid (DNA) damage in targeted cancer cells by interfering with the action of topoisomerase II, a critical enzyme enabling cell proliferation. Berubicin treatment of brain cancer patients appeared to demonstrate positive responses that include one durable complete response in a Phase 1 human clinical trial conducted by Reata Pharmaceuticals, Inc. Berubicin, was developed by Dr. Waldemar Priebe, Professor of Medicinal Chemistry at The University of Texas MD Anderson Cancer Center.

On June 23, 2022 DEM BioPharma, Inc. (DEM Bio), an immuno-oncology company developing therapies that target novel innate immune system checkpoints to eliminate cancer, reported its initial $70 million financing led by founding investor Longwood Fund and Alta Partners, with additional participation from Insight Partners, Pfizer Ventures, Astellas Venture Management, Emerson Collective, UTokyo Innovation Platform and Alexandria Venture Investments (Press release, DEM BioPharma, JUN 23, 2022, View Source [SID1234616205]).

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DEM Bio is pioneering the next generation of immunotherapeutics designed to unleash macrophages and other myeloid effector cells to eliminate tumors by targeting novel ‘don’t eat me’ (DEM) and ‘eat me’ (EM) signals on cancer cells and macrophages. The company’s approach builds on the groundbreaking research from its scientific co-founders:

Jonathan Weissman, Ph.D. – Whitehead Institute, National Academy of Sciences member, HHMI, world leader in genome-wide CRISPR screens;
Michael Bassik, Ph.D. – Stanford University, a distinguished biologist in cancer, phagocytes, and CRISPR screening; and
Kipp Weiskopf, M.D., Ph.D. – Whitehead Fellow and physician at Dana-Farber Cancer Institute, one of the world’s leaders in macrophage and cancer biology.
DEM Bio is focused on accessing the largely untapped opportunity around macrophage biology and innate immune system pathways to discover potent DEM and EM signals on cancers and expand the therapeutic potential of the field beyond the relatively small number of signals targeted by current investigational therapies. The company’s proprietary CHoMP platform (Co-culture with Human Myeloid Phagocytes) will be used to identify unexplored DEM and EM signals in a systematic and unbiased manner via inter-cellular CRISPR screening using tumor cells, primary macrophages, and other innate immune effector cells.

DEM Bio also announced the appointment of Jan Skvarka, former CEO of Trillium Therapeutics (acquired by Pfizer for $2.22 billion in November 2021), as Executive Chairman. As part of the financing, Christoph Westphal, M.D., Ph.D., Founding CEO, DEM Bio, and Founding Partner Longwood Fund; Dan Janney, Managing Partner, Alta Partners; Dylan Morris, Managing Director, Insight Partners; Marie-Claire Peakman, Ph.D., Principal, Pfizer Ventures; and Hiro Kimura, Ph.D., Investment Director, Astellas Venture Management have joined DEM Bio’s Board of Directors.

"Currently known DEM signals have been described in an ad hoc manner. DEM Bio’s founders discovered a scalable approach to systematically unlock the potential of innate immune system checkpoints," noted Dr. Westphal.

"This financing from an exceptional group of investors positions us to execute on our ambitious plans to develop the next generation of macrophage checkpoint inhibitors that may revolutionize how we treat cancer," said Mr. Skvarka.

DEM Bio has assembled a world-class Scientific Advisory Board consisting of leaders in the field of CRISPR high-throughput screening, immune phagocytes, cancer biology, and therapeutic development, including co-founders Drs. Weissman, Bassik and Weiskopf, Roarke Kamber, Ph.D., Postdoctoral fellow, Genetics, Stanford School of Medicine, Dian Yang, Ph.D., Postdoctoral fellow, Whitehead Institute for Biomedical Research, as well as Kai Wucherpfennig, M.D., Ph.D., Professor and Chair, Dana-Farber Cancer Institute; Dane Wittrup, Ph.D., Professor of Chemical Engineering & Bioengineering, MIT; and Bob Uger, Ph.D., former CSO, Trillium Therapeutics.

"The currently known DEM and EM pathways were discovered serendipitously," said Dr. Bassik. "Similar to other areas of immunotherapy, there are likely other signals that are more potent and offer better therapeutic targets, but no one has yet taken a systematic approach to identifying those pathways."

"By leveraging cutting-edge functional genomics and macrophage biology, we created the CHoMP platform to discover new DEM/EM signals in a fully unbiased and systematic way," said Dr. Weiskopf.

"CHoMP is a highly differentiated platform built on unique, proprietary CRISPR screening capabilities in primary human cells, enabling DEM Bio to methodically evaluate unexplored DEM/EM signals," said Dr. Weissman.

The CHoMP platform has identified a number of promising new DEM/EM signals, including the novel DEM pathway APMAP. In preclinical work, targeting APMAP enhanced tumor cell phagocytosis in multiple cancer cell types and animal cancer models, and demonstrated synergistic effects with a broad range of tumor-binding antibodies.

David Donabedian, Co-founder and start-up CEO of DEM Bio, and Operating Partner, Longwood Fund added, "APMAP is just one of the promising programs identified using the CHoMP platform, and the encouraging initial data on this pathway has helped validate our differentiated approach to identifying novel, potent DEM/EM signals. The company plans to use proceeds from this financing to further develop our platform and to advance our portfolio of novel targets towards therapeutic development in oncology."

On June 23, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) applications for [225Ac]-FPI-2059 (FPI-2059) and the corresponding imaging analogue [111In]-FPI-2058 (FPI-2058). FPI-2059 is a targeted alpha therapy (TAT) designed to use a small molecule to target and deliver actinium-225 to tumor sites expressing neurotensin receptor 1 (NTSR1), a protein that is overexpressed in multiple solid tumor types, including colorectal, pancreatic, gastric, neuroendocrine differentiated prostate, head and neck squamous cell carcinoma, and Ewing sarcoma cancers (Press release, Fusion Pharmaceuticals, JUN 23, 2022, View Source [SID1234616221]).

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"The FPI-2059 program showcases Fusion’s ability to use our platform technology and R&D expertise to efficiently convert different classes of targeting molecules into TATs against innovative targets that are designed to address cancers with high unmet need," said John Valliant, Ph.D. "With FPI-2059, we believe there is significant opportunity to address multiple solid tumor types, including neuroendocrine differentiated prostate cancer where PSMA expression is typically low and therefore patients are not adequately treated by existing radioligand therapies. We look forward to progressing FPI-2059, Fusion’s first small molecule-based TAT and third clinical program, into a Phase 1 study."

Fusion acquired [177Lu]-IPN-1087 (IPN-1087), a lutetium-based beta-emitting radiopharmaceutical, from Ipsen in April 2021, and converted the compound to the alpha-emitting [225Ac]-FPI-2059. In clinical studies, IPN-1087 showed promising early safety data and good uptake in multiple tumor types. In a head-to-head in vivo comparison of therapeutic efficacy in a mouse xenograft model of colorectal cancer between FPI-2059 and IPN-1087, results show tumor regression with FPI-2059 is achieved at doses of approximately 1500 times lower than IPN-1087.

Fusion plans to initiate a Phase 1, non-randomized, open-label clinical trial in patients with solid tumors expressing NTSR1, intended to investigate safety, tolerability and pharmacokinetics and to establish the recommended Phase 2 dose. The study will prioritize six solid tumor indications, including head and neck squamous cell carcinoma, pancreatic, neuroendocrine prostate, colorectal, gastric and Ewing sarcoma. The study employs a 3 + 3 dose escalation design to evaluate multiple ascending doses of FPI-2059. As part of the screening process, patients will be administered an imaging analogue of FPI-2059, FPI-2058, and only those who meet predefined tumor uptake and safety criteria will go on to receive FPI-2059.

Radiopharmaceuticals are a precision medicine in that the alpha therapeutic can be converted into a corresponding imaging analogue with a different radionuclide (in this case indium), used to screen for a biomarker in patients with tumors that express the cancer target, increasing the likelihood of response to therapy. Fusion plans to provide additional guidance on timelines for the FPI-2059 program following initial experience with patient screening in order to better predict the cadence of patient enrollment.

About FPI-2059
[225Ac]-FPI-2059 (FPI-2059) is a targeted alpha therapy combining actinium-225 with a small molecule designed to target neurotensin receptor 1 (NTSR1), in development as a potential treatment for various solid tumors. NTSR1 is a promising target for cancer treatment that is overexpressed in multiple solid tumors including colorectal, pancreatic, gastric, neuroendocrine differentiated prostate, head and neck squamous cell carcinoma and Ewing sarcoma cancers. FPI-2059 is currently being evaluated in a Phase 1 study.

On June 23, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision-oncology biopharmaceutical company, reported that the first patient has been enrolled in a multicenter phase 2 clinical trial evaluating its spleen tyrosine kinase (SYK) inhibitor mivavotinib (CB-659) in patients with relapsed/refractory non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL), a DLBCL subpopulation that primarily comprises patients with activated B-cell like disease (ABC) (Press release, Calithera Biosciences, JUN 23, 2022, View Source [SID1234616206]).

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In a retrospective analysis of prior phase 1/2 studies in patients with DLBCL, patients with non-GCB DLBCL who received mivavotinib had a response rate of 53%, as compared to a response rate of 22% in patients with GCB DLBCL. Additionally, recent preclinical studies have shown enhanced SYK activity, and greater sensitivity to SYK inhibition, in DLBCL tumor-cell lines with mutations in MYD88 and CD79b genes. A significant fraction of patients with non-GCB DLBCL have tumors that harbor these mutations, and this subset of patients is known to have poorer outcomes with standard-of-care therapies.

"Mivavotinib has demonstrated potential to be a first-to-market approach for non-GCB DLBCL, including the genetic subset of patients harboring MYD88 and/or CD79 mutations," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "This study will advance understanding of how our novel biomarker-driven approach could help address this high unmet therapeutic need, and we look forward to sharing data by the first quarter of 2023."

The phase 2 clinical trial (NCT05319028) is an open-label study of mivavotinib monotherapy in patients with relapsed/refractory non-GCB DLBCL. The main study objectives are to confirm previously seen single-agent activity in non-GCB DLBCL patients, evaluate activity according to MYD88/CD79b mutational status, and refine dose/schedule in this patient population. Approximately 50 non-GCB DLBCL patients, with or without MYD88/CD79b mutations, will be randomized 1:1 to one of two oral dose/schedule cohorts: a continuous dosing schedule (100 mg QD) or an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15).

Centrally assessed ctDNA-based liquid next-generation sequencing (NGS) will be performed after randomization to ascertain MyD88/CD79b mutation status. The primary endpoints of the study are overall response rate as assessed by an independent radiology review committee and safety. Key secondary endpoints include duration of response, progression-free survival, and complete response.

Data from the trial could position Calithera to initiate a study with registrational intent in biomarker-specific DLBCL populations.