On June 20, 2022, Celldex Therapeutics Inc. (the "Company") reported that entered into a binding settlement term sheet (the "Term Sheet") with Shareholder Representatives Services LLC ("SRS"), relating to the previously disclosed litigation brought by the Company (the "Litigation") arising under the Agreement and Plan of Merger, dated November 1, 2016 (the "Merger Agreement"), by and among Kolltan Pharmaceuticals, Inc., the Company, Connemara Merger Sub 1 Inc., Connemara Merger Sub 2 LLC and SRS, solely in its capacity as the Stockholders Representative, which, upon execution of a definitive settlement agreement and the payment of the Initial Payment (as defined below), will result in the joint dismissal, with prejudice, of all claims and counterclaims in the Litigation (Filing, 8-K, Celldex Therapeutics, JUN 20, 2022, View Source [SID1234616207]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pursuant to the terms of the Term Sheet, all milestone payments provided for by the Merger Agreement are replaced in their entirety with the following payments, each of which is payable only once:

(i)The Company shall pay $15,000,000 upon execution of the Settlement Agreement (the "Initial Payment").
(ii)The Company shall pay $15,000,000 upon the Successful Completion (as defined in the Term Sheet) of a Phase 2 Clinical Trial (as defined in the Merger Agreement) of CDX-0159, subject to the $2,500,000 contractual credit as set forth in the Merger Agreement.
(iii)The Company shall pay $52,500,000 upon the first United States Food and Drug Administration or European Medicines Agency, or, in each case, any successor organization, regulatory approval of a Surviving Company Product (as defined the Term Sheet).

The above payment obligations replace, in their entirety, the contingent consideration in the form of development, regulatory approval and sales-based milestones of up to $172.5 million contained in the Merger Agreement.

Each of the Company and SRS will provide broad mutual releases of all claims relating to or arising out of the Merger Agreement, including without limitation, all claims brought in the Litigation or that could have been brought in the Litigation. The Term Sheet is binding pending the execution of a formal settlement agreement on or before July 15, 2022.

The Company has elected to pay the Initial Payment in cash. When and if any of the remaining payments described above become due, they shall be payable, at the Company’s sole election, in either cash or stock (as set forth in the Merger Agreement) or a combination thereof.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 Athenex (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported that Daniel Lang, M.D., President, Athenex Cell Therapy, will participate in The Next Cells & Mechanisms to Watch in Oncology panel at the Truist Securities Cell Therapy Symposium on Tuesday, June 28, 2022 at 11:30 am Eastern Time in New York, NY (Press release, Athenex, JUN 23, 2022, View Source [SID1234616203]). Company management will also participate in one-on-one investor meetings during the event.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Registration is available on the Truist symposia-cel website. An audio archive of the webcast will be available in the "Events and Presentations" section of the Athenex website for the following 90 days.