On December 9, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported new preclinical and preliminary clinical results for ATA2271, a next-generation autologous chimeric antigen receptor (CAR) T-cell therapy targeting mesothelin (MSLN) (Press release, Atara Biotherapeutics, DEC 9, 2021, View Source [SID1234596690]). These promising early safety and functional persistence data were presented by collaborators at Memorial Sloan Kettering Cancer Center as a mini-oral session at the European Society for Medical Oncology Immuno-Oncology (ESMO I‑O) Congress 2021, in Geneva, Switzerland.

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ATA2271 is an investigational, autologous, second-generation CAR-T immunotherapy that is designed to treat certain aggressive solid tumors, including malignant pleural mesothelioma (MPM). Even with successful completion of a combination of chemotherapy, aggressive surgical resection and radiation therapy, the median survival of treated patients in this report is only 9-17 months. ATA2271 incorporates Atara’s novel inclusion of armoring, in the form of a PD-1 DNR construct, to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR to enhance expansion and functional persistence of the CAR T-cells.

"CAR T-cell therapies have made incredible in-roads in the treatment of hematological malignancies, but new technology and targeting approaches are needed to apply these gains to aggressive solid tumors," said Cokey Nguyen, Senior Vice President and Chief Scientific Officer at Atara. "We are extremely encouraged by these early data assessing ATA2271 in advanced mesothelioma from a first-in-human (FIH) Phase 1 study. Early findings represent the first report of CAR T cells persisting over four weeks in a solid tumor microenvironment without need for additional agents, such as checkpoint inhibitors."

As reported in the full abstract available on the ESMO (Free ESMO Whitepaper) website, results from the evaluation of ATA2271 demonstrate the safety, functional persistence and activation of the CAR T cells. These studies, led by Prasad S. Adusumilli, MD, and collaborators at MSK provide both in vitro and in vivo evidence of the preclinical safety, improved functional characteristics and enhanced anti-tumor efficacy of ATA2271 and promising preliminary safety and persistence data in patients with MPM.

Specifically, in vitro functional studies show potent antitumor activity of ATA2271 following repeat antigen stimulation, with enhanced expansion observed in cells equipped with a PD-1 dominant negative receptor (PD1DNR) that provides T-cell intrinsic checkpoint blockade compared to CAR T-cells with a modified CD3z (1XX) alone. These data support the design of ATA2271, which expresses a dominant negative version of PD-1 receptor, to maintain function in the presence of suppressive checkpoint ligands commonly associated with solid tumor microenvironments. In addition, results further support the combination of next-gen CAR design (1XX) plus PD1 DNR armoring technology in differential enrichment of cytokine production involving cytokine signaling, effector immune responses, leukocyte activation and differentiation. Furthermore, in vivo, intrapleural administration of ATA2271 CAR T-cells in mice (n=8) eradicated mesothelioma and prolonged survival. Functional persistence of ATA2271 in vivo was evident by resistance to tumor reestablishment following 10 rechallenges.

In the ongoing Phase 1 dose finding study (NCT04577326), intrapleural administration of ATA2271 was found to be well-tolerated at lowest dose levels with no CAR T-cell related adverse events (AEs) of Grade >2 observed and no AEs of Grade >3 to date in the study. All four patients had received at least four prior lines of therapy. Importantly, ATA2271 CAR T-cells persisted in patients’ peripheral blood for greater than four weeks and was associated with upregulated effector cytokines.

Mini-Oral Presentation Details:

Title: Promoting Functional Persistence in Solid Tumor CAR T-cell Therapy: Mesothelin-targeted CAR (M28z1XXPD1DNR) with T-cell Intrinsic PD1 Dominant Negative Receptor

Presenting Author: Prasad S. Adusumilli, MD, FACS, Memorial Sloan Kettering Cancer Center, New York, NY
Date & Time: Thursday, December 9, 2021, at 11:05 a.m. CET / 5:05 a.m. EST / 2:05 a.m. PST
Abstract Number: 46MO
Session: Mini Oral Session
Location: Palexpo Congress Centre, Room C
About Atara’s Mesothelin CAR T Franchise

Atara’s preclinical pipeline is rapidly expanding with novel technologies and next-generation, multi-targeted CAR T immunotherapies through collaborations with Moffitt Cancer Center and Memorial Sloan Kettering Cancer Center.

In December 2020, Bayer and Atara announced an exclusive worldwide license agreement for next-generation, mesothelin-directed CAR T-cell therapies for the treatment of solid tumors. The agreement includes the development candidate ATA3271, an armored next generation allogeneic T-cell immunotherapy, and an autologous version, ATA2271, for the treatment of high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small cell lung cancer.

Both ATA2271 and ATA3271 incorporate Atara’s novel inclusion of armoring in the form of a PD-1 DNR construct to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR to enhance expansion and functional persistence of the CAR T-cells. ATA3271 leverages Atara’s EBV T-cell platform and is currently in IND-enabling studies.

MSK Disclosures: Dr. Prasad S. Adusumilli has intellectual property interests and other financial interests related to Atara. MSK has intellectual property rights and associated interests by virtue of licensing agreements between MSK and Atara.

On December 9, 2021 Sapience Therapeutics, Inc., a biotechnology company focused on the discovery and development of peptide therapeutics to address difficult-to-treat cancers, reported that it will present multiple posters on its lead program, ST101, at the 2021 San Antonio Breast Cancer Symposium, being held in San Antonio, Texas in a hybrid format (in-person and virtual), December 7-10, 2021 (Press release, Sapience Therapeutics, DEC 9, 2021, View Source [SID1234596689]).

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Presentation details for the posters are as follows:

Presentation Title: Phase 1 study of ST101, a first-in-class peptide antagonist of CCAAT/-binding protein β (C/EBPβ), in patients with advanced solid tumors, with a phase 2 expansion in patients with hormone receptor positive breast cancer (HR+ BC)
Date/Time: Thursday, December 9, 2021 5:00 PM-6:30 PM CT

Presentation Title: C/EBPβ antagonist peptide, ST101, as a novel therapeutic for breast cancer
Date/Time: Friday, December 10, 2021 7:00 AM-8:30 AM CT

About ST101
ST101, a peptide antagonist of C/EBPβ, is currently being evaluated in an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). In the ongoing study, ST101 has demonstrated clinical proof-of-concept with a RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. Following conclusion of the final dose-escalation cohort, Sapience plans to initiate four Phase 2 expansion cohorts in refractory, locally advanced and metastatic cutaneous melanoma, hormone-receptor-positive breast cancer, castrate-resistant prostate cancer, and glioblastoma starting in the second half of 2021. ST101 has been granted orphan drug product designation from the U.S. Food and Drug Administration and orphan medicinal product designation for the treatment of glioma by the European Commission.

On December 9, 2021 Bavarian Nordic A/S (OMX: BAVA) ("Bavarian Nordic" or the "Company") reported that it has in connection with the directed issue and private placement registered with the Danish Business Authority, a capital increase of a nominal value of DKK 63,736,800 (6,373,680 shares of DKK 10 each) (the "New Shares"), representing 9.94% of the registered share capital prior to the capital increase (the "Offering") (Press release, Bavarian Nordic, DEC 9, 2021, View Source [SID1234596688]).

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The New Shares have been issued under a temporary ISIN code and are expected to be admitted to trading and official listing under the permanent ISIN code DK0015998017 on Nasdaq Copenhagen A/S with effect from 10 December 2021. After registration of the share capital increase, the share capital of Bavarian Nordic amounts to nominally DKK 704,683,930 divided into 70,468,393 shares of DKK 10 each. The total number of voting rights in Bavarian Nordic are 70,468,393.

The New Shares rank pari passu with the Company’s existing shares and carry the same dividend and other rights. Each New Share carries one vote at the Company’s general meetings.

Reference is made to company announcements no. 40 and 41 of 6 December 2021.

The amendments to the Company’s articles of association required by the capital increase have been registered today with the Danish Business Authority and an updated version can be found at bavarian-nordic.com.

JOINT GLOBAL COORDINATORS AND JOINT BOOKRUNNERS
Citigroup Global Markets Limited and Nordea Danmark, filial af Nordea Bank Abp, Finland acted as Joint Global Coordinators and Joint Bookrunners in connection with the Offering (jointly the "Joint Global Coordinators and Joint Bookrunners").

Kromann Reumert and Latham & Watkins LLP acted as Danish and U.S. legal advisors respectively to the Company. Plesner acted as Danish legal advisors to the Joint Global Coordinators and Joint Bookrunners.

On December 9, 2021 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported a series of events in December 2021 that will highlight various aspects of its DARPin cancer therapeutic portfolio (Press release, Molecular Partners, DEC 9, 2021, View Source [SID1234596685]). These events include a presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology (ESMO-IO) Congress, focused on the clinical-stage fibroblast activation protein (FAP)-targeted CD40 activator candidate, MP0317; a presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, focused on MP0533, the company’s acute myeloid leukemia (AML) candidate, designed to simultaneously engage CD3 on T cells and target three tumor associated antigens (TAAs); and a comprehensive review of the company’s cancer portfolio and its research & development strategy at a virtual Oncology Day to be held at 8:30 am ET on December 15, 2021.

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"Our growing understanding of cancer biology enables us to expand and enhance our oncology portfolio. We carefully analyze clinical results of antibodies, their targets, and the underlying biology, with a focus on near misses. We then apply our DARPin technology to overcome these problems to offer solutions to patients in need," said Patrick Amstutz, Ph.D., CEO of Molecular Partners. "Data shared this month will show how our current cancer therapeutic portfolio addresses difficult targets and modes of action. At our Oncology Day, we will discuss further extensions of our platform in cancer as part of our corporate strategy to build out our offering in areas where the unique DARPin protein drug class can make a meaningful impact for patients."

Details of the events follow:

ESMO Immuno-Oncology (onsite and online congress), Geneva, Switzerland; December 8-11, 2021
At ESMO (Free ESMO Whitepaper)-IO, Molecular Partners will focus on MP0317, which targets both fibroblast activation protein (FAP) and the immunostimulatory protein CD40 to enable tumor-localized immune activation in solid tumors. Through this mechanism, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to other CD40-targeting agents. MP0317 is the second DARPin immuno-oncology therapeutic candidate to enter clinical trials. Its Phase 1 first-in-human clinical study design includes collection of a wide array of biomarkers to support the establishment of combination therapies in specific indications.

A poster reviewing the MP0317 Phase 1 study will be on display throughout the conference.
A presentation on MP0317 will be presented on December 10:
Title: The development of MP0317 FAP X CD40 agonist DARPin
Educational Session: Emerging Immunotherapy platforms: From bispecifics to cell transfer therapy
Date: Friday, December 10
Time: 5:00-6:30 pm ET
Location: Virtual / Hall C
63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition, Atlanta, Georgia, U.S.; December 11-14, 2021
At ASH (Free ASH Whitepaper), Molecular Partners will focus on MP0533, its DARPin candidate for acute myeloid leukemia (AML). MP0533 is designed to target AML cells, especially leukemic stem cells (LSCs), via the three tumor-associated antigens CD33, CD70 and CD123, and bind CD3 on T cells to induce tumor cell killing. MP0533 preferentially targets AML cells via an avidity dependent mechanism which increases the candidate’s total binding strength when two or more antigens are bound. This leads to T-cell mediated killing of these malignant cells upon CD3 engagement, while healthy cells, which express only one of these targets or none, are left unharmed.

In previously reported preclinical work, Molecular Partner’s AML program has demonstrated the potential to improve upon the therapeutic window of CD3-activated T cell engagers through reducing dose-limiting toxicity via its unique avidity-driven targeting mechanism. The research at ASH (Free ASH Whitepaper) will review prior work from the program and share new ex vivo and in vivo studies supporting MP0533’s anti-tumor activity and enhanced therapeutic window, relative to another CD3-activating molecule. More specifically, we will show that MP0533 is able to induce the killing of AML patients’ malignant cells by the patients’ own T cells, demonstrating that AML patients could respond to MP0533 despite a potentially weaker T cell response. We will further demonstrate that such an efficacy may be achieved without impacting the safety profile of MP0533, as demonstrated by specific killing of LSCs while preserving healthy hematopoietic stem cells. Clinical development of MP0533 is expected to initiate in 2022.

A poster reviewing the preclinical development of MP0533 will be displayed on December 11 accompanied by an oral presentation.
Title: Avidity-Engineered CD3 Engaging DARPin Targeting Three Tumor Associated Antigens Induce Strong and Specific T Cell Dependent Killing of AML Cells with Potential for Improved Safety
Session: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Date: Saturday, December 11, 2021
Time: 5:30 PM – 7:30 PM ET
Location: Virtual / Georgia World Congress Center, Hall B5

Molecular Partners Virtual Oncology Day (online only), 8:30 am ET, December 15. Register here.
Molecular Partners will host a virtual session with its management team focused on cancer portfolio and strategy, including MP0310, MP0317, MP0533 and additional research programs. After a brief corporate review, the session will explore the underlying biology, candidate design and preclinical data supporting each oncology or immuno-oncology program, as well as the underlying development strategy and new opportunities for the portfolio. Molecular Partners management will be joined by leading AML experts Professors Ochsenbein and Riether from the University of Bern.

Relevant materials from the above events will be shared via Molecular Partners’ website investor portal at investors.molecularpartners.com.

On December 9, 2021 Investigators from US Oncology Research, The US Oncology Network (The Network), and OntadaTM reported that it will share results from more than 30 studies exploring areas such as diffuse large B cell lymphoma, non-Hodgkin lymphoma, multiple myeloma and hematological adverse event management in the community oncology setting at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, US Oncology, DEC 9, 2021, View Source [SID1234596681]). The ASH (Free ASH Whitepaper) Annual Meeting, a leading scientific event in malignant and non-malignant hematology, will take place in Atlanta, Georgia and virtually from Dec. 11-14, 2021.

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"We are making tremendous strides in caring for a wide array of hematological malignancies, including hard-to-treat blood cancers, and have much more to offer patients than in years past. However, there is still need for advances," said Robert L. Coleman, MD, FACOG, FACS, chief scientific officer, US Oncology Research. "We are excited about presenting our latest findings and coming back together with the community as we continue to learn, collaborate and innovate towards improved patient outcomes."

In a late-breaking abstract session on Tuesday, Dec. 14 from 9:00 am to 10:30 am ET, results will be presented from "The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma."

"Approximately 40 percent of patients with newly diagnosed diffuse large B-cell lymphoma are not cured with the current standard of care regimen known as R-CHOP," said study co-author John Burke, MD, a hematologist with Rocky Mountain Cancer Centers, a practice in The Network. "In the Phase 3 POLARIX study, we compared a combination of the CD79b-targeting antibody–drug conjugate, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone, or pola-R-CHP, with R-CHOP. The results of the POLARIX study may have significant implications for the way we treat diffuse large B-cell lymphoma in the front-line setting in the future and look forward to the findings being shared at the ASH (Free ASH Whitepaper) Meeting."

Additionally, Dr. Burke will present an abstract titled, "Efficacy and Safety of Umbralisib, Ublituximab (U2), and U2 Plus Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)," in an oral presentation Sunday, Dec. 12 at 5:30 pm.

"Patients with relapsed or refractory DLBCL generally have a poor prognosis, particularly if they are not candidates for autologous stem cell transplantation or experience relapse following approved CAR-T therapies. In the UNITY-NHL study, we systematically explored the efficacy and tolerability of the PI3K-d/CK1-e inhibitor, umbralisib, alone, and in combination with the glycoengineered anti-CD20 monoclonal antibody ublituximab, followed by a cohort treated with umbralisib, ublituximab and bendamustine," said lead author Dr. Burke. "We found that the triplet regimen was effective and well tolerated in patients with relapse or refractory DLBCL who were unsuitable for transplant or who had relapsed following transplant."

In an oral abstract session on Monday, Dec. 13 at 4:45 pm, results will be presented from the study, "Completed Induction Phase Analysis of Magnify: Phase 3b Study of Lenalidomide + Rituximab (R2) Followed By Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma."

"Unfortunately, people with relapsed indolent non-Hodgkin lymphoma have limited standard treatment options," said study co-author David Andorsky, MD, hematologist with Rocky Mountain Cancer Centers. "Therefore, our analysis from the induction phase of the Phase 3b MAGNIFY trial which provides additional evidence that lenalidomide combined with rituximab is active with a tolerable safety profile in a wide range of patients with relapsed or refractory disease is encouraging."

Jerome Goldschmidt, MD, oncologist at Blue Ridge Cancer Care, a practice in The Network, will present results during a poster presentation titled, "Understanding Hematological Adverse Event Management through Health Care Resource Utilization, Costs, and Treatment Patterns of Patients with Extensive-Stage Small Cell Lung Cancer Treated in the Community Oncology Setting," on Saturday, Dec. 11 from 5:30 pm to 7:30 pm. Dr. Goldschmidt, lead author of the abstract, worked with Ontada researchers on this retrospective, observational study. Ontada is an oncology real-world data and evidence, clinical education and provider technology business dedicated to improving the lives of cancer patients.

"Our study found that there is significant burden of myelosuppressive hematological adverse events among extensive stage small cell lung cancer patients in the community oncology setting. Notably, patients with grade ≥3 hematological adverse events appear to have more dose reductions, treatment delays and healthcare service utilizations than those without," said Dr. Goldschmidt. "Future research should strive to understand the full scope of hematologic adverse event management and define the role therapies that protect bone marrow from these adverse events can play in reducing this burden."

Robert Rifkin, MD, medical director of biosimilars for McKesson, associate chair of hematology research and myeloma disease lead for The US Oncology Network, and hematologist with Rocky Mountain Cancer Centers, co-authored an analysis of outcomes among people with triple-class refractory multiple myeloma titled, "Real-World Treatment Patterns and Clinical, Economic, and Humanistic Burden in Triple-Class Refractory Multiple Myeloma: Analysis of the Connect Multiple Myeloma (MM) Disease Registry." The oral presentation will take place on Saturday, Dec. 11 at 10:00 am.

"Treatment resistance remains a challenge for most multiple myeloma patients and their outcomes and health-related quality of life worsens with each line of therapy. Patients who are refractory to immunomodulatory drugs, proteasome inhibitors and anti-CD38 antibodies, or triple-class refractory, have an especially bleak prognosis and high disease burden," said Dr. Rifkin. "Data presented from the ongoing prospective Connect MM Disease Registry confirm that people with triple-class refractory multiple myeloma experience poor survival, substantial hospitalizations and a clinically meaningful decline in health-related quality of life and suggest that novel tolerable and efficacious therapeutic agents are urgently needed to address the burden of illness in triple-refractory multiple myeloma."

The full schedule of affiliated data presentations, including timing and author information, can be found here. For more information or to interview a trial investigator, contact Claire Crye at 281.825.9927 or [email protected] or Edie DeVine at 209.814.9564 or [email protected].