On February 17, 2022 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported financial results for the fourth quarter and full year 2021 (Press release, Prothena, FEB 17, 2022, View Source [SID1234608258]). In addition, the Company provided 2022 financial guidance and an update on business highlights.

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"Prothena made meaningful progress in multiple therapeutic indications across our portfolio in 2021 with the advancement of three clinical stage programs. We announced the initiation of the confirmatory Phase 3 AFFIRM-AL study of birtamimab, Phase 2b PADOVA study of prasinezumab, and Phase 1 study of PRX005. Additionally, we presented positive preclinical findings for our anti-Aβ PRX012 and our dual Aβ/tau vaccine at AAIC in June last year," said Gene Kinney, Ph.D., President and Chief Executive Officer of Prothena. "In 2021, we also received $200 million from strategic partnerships with leading pharmaceutical companies and bolstered our cash position with $175 million raised through equity offerings. In 2022, we look forward to multiple scientific congresses starting with the presentation of additional preclinical data at AD/PD in March. Our strong capital position funds Prothena through multiple value-creating milestones as we transition into a fully integrated commercial company."

2021 Business Highlights and Upcoming Milestones

Neurodegenerative Diseases Portfolio

Alzheimer’s Disease (AD)

PRX012, a potential best-in-class treatment for AD, is an investigational monoclonal antibody targeting a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency

•Presented preclinical results at the Alzheimer’s Association International Conference in 2021 (AAIC) demonstrating that PRX012 significantly cleared both pyroglutamate-modified and -unmodified Aβ plaque in post-mortem brain tissue of late-stage AD patients
•Investigational New Drug (IND) application filing expected 1Q 2022

PRX005, a potential best-in-class treatment for AD, is an investigational antibody that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in diseases including AD, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), and other tauopathies. PRX005 is part of the global neuroscience research and development collaboration with Bristol Myers Squibb

•Received $80 million option payment from Bristol Myers Squibb for execution of U.S. license agreement in 2021
•Phase 1 study initiated in 2021
•Topline Phase 1 data expected in 2022

Dual Aβ/tau vaccine, a potential first-in-class treatment and prevention for AD, is a dual-target vaccine targeting key epitopes within the Aβ and tau proteins to promote amyloid clearance and blockade of pathogenic tau

•AAIC presentation in 2021 showcased preclinical data demonstrating that Prothena’s dual Aβ/tau vaccine generated appropriate and balanced antibody titers promoting both phagocytosis of Aβ plaque and blockade of tau transmission in vitro
•Presentation of preclinical data at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) expected in March 2022
•IND filing expected in 2023

Parkinson’s Disease (PD)

Prasinezumab, a potential first-in-class treatment for PD, is a humanized monoclonal antibody designed to target key epitopes within the C-terminus of alpha-synuclein and is the focus of the worldwide collaboration with Roche
•Earned $60 million clinical milestone payment in 2021 upon dosing of the first patient in the global Phase 2b PADOVA study for prasinezumab (NCT#04777331)
•Presentation of additional data by Roche at AD/PD expected in March 2022
•Phase 2b PADOVA study results expected in 2024

Rare Peripheral Amyloid Diseases Portfolio

AL Amyloidosis (AL)

Birtamimab, a potential best-in-class amyloid depleter treatment for AL, is an investigational humanized monoclonal antibody designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid that causes organ dysfunction and failure

•Reached Special Protocol Assessment (SPA) agreement with FDA at p≤0.10 and initiated confirmatory Phase 3 AFFIRM-AL study of birtamimab in Mayo Stage IV patients with AL amyloidosis in 2021 (NCT#04973137)
•Confirmatory Phase 3 AFFIRM-AL study results expected in 2024

ATTR Amyloidosis (ATTR)

PRX004, a potential first-in-class treatment for ATTR, is a humanized monoclonal antibody designed to deplete the pathogenic, non-native forms of the TTR protein, and is being developed by Novo Nordisk for the treatment of ATTR cardiomyopathy

•Announced Novo Nordisk acquisition of ATTR business for a total aggregate of up to $1.23 billion and Prothena received $60 million up front payment in 2021
•Novo Nordisk expected to initiate a Phase 2 trial in 1H 2022 with PRX004 for the treatment of ATTR cardiomyopathy

2021 Organizational Highlights

•Sanjiv Patel, MBBS, MA, MBA, appointed to the Board of Directors
•Hideki Garren, M.D., Ph.D., appointed to Chief Medical Officer
•Tran Nguyen, Chief Financial Officer, appointed to the additional, newly created role of Chief Strategy Officer
•Brandon Smith promoted from Chief Business Officer to Chief Operating Officer

Upcoming Investor Conference

Members of the senior management team will present and participate in investor meetings at the following upcoming investor conference:

•Oppenheimer 32nd Annual Healthcare Conference, March 15, 2022, at 1:20 PM ET

Fourth Quarter and Full Year of 2021 Financial Results
For the fourth quarter and full year of 2021, Prothena reported a net loss of $33.2 million and net income of $67.0 million, respectively, as compared to a net loss of $30.7 million and $111.1 million for the fourth quarter and full year of 2020, respectively. Net loss per share for the fourth quarter of 2021 was $0.71 and net income per share on a diluted basis for the full year of 2021 was $1.38, as compared to net loss per share of $0.77 and $2.78 for the fourth quarter and full year of 2020, respectively.
Prothena reported total revenue of $1.2 million and $200.6 million for the fourth quarter and full year of 2021, respectively. Revenue for the fourth quarter of 2021 related to $1.2 million from Bristol Myers Squibb. Revenue for the full year of 2021, included $79.7 million from Bristol Myers Squibb for PRX005 U.S. License and U.S. Development Services and $60.7 million from the sale of the intellectual property and related rights to the Company’s ATTR amyloidosis business and pipeline to Novo Nordisk. In addition, the full year revenue included $60.0 million in clinical milestone payment from Roche related to the global Phase 2b PADOVA study for prasinezumab and a nominal amount of license revenue from Roche. This compares to total revenue of $0.4 million and $0.9 million for the fourth quarter and full year of 2020, primarily from collaboration revenue from Roche.

Research and development (R&D) expenses totaled $22.1 million and $82.3 million for the fourth quarter and full year of 2021, respectively, as compared to $20.8 million and $74.9 million for the fourth quarter and full year of 2020, respectively. The increase in R&D expense for the fourth quarter and full year of 2021 compared to the same periods in the prior year was primarily due to higher personnel expenses, higher clinical trial expenses primarily related to the birtamimab and PRX005 programs (offset in part by lower PRX004 clinical trial expense); offset in part by lower collaboration expenses related to the prasinezumab program with Roche as a result of the cost share opt-out exercised in May 2021 and lower manufacturing costs primarily related to PRX005 and birtamimab programs (offset in part by higher PRX012 preclinical expense). R&D expenses included non-cash share-based compensation expense of $2.9 million and $9.5 million for the fourth quarter and full year of 2021, respectively, as compared to $2.1 million and $8.2 million for the fourth quarter and full year of 2020, respectively.
General and administrative (G&A) expenses totaled $12.2 million and $46.3 million for the fourth quarter and full year of 2021, respectively, as compared to $9.9 million and $38.7 million for the fourth quarter and full year of 2020, respectively. The increase in G&A expenses for the fourth quarter and full year of 2021 compared to the same periods in the prior year was primarily related to higher personnel expenses, legal expenses, consulting and expense for our director and officer insurance premium. G&A expenses included non-cash share-based compensation expense of $4.0 million and $15.1 million for the fourth quarter and full year of 2021, respectively, as compared to $3.2 million and $13.8 million for the fourth quarter and full year of 2020, respectively.
Total non-cash share-based compensation expense was $6.9 million and $24.7 million for the fourth quarter and full year of 2021, respectively, as compared to $5.2 million and $22.0 million for the fourth quarter and full year of 2020.

As of December 31, 2021, Prothena had $580.4 million in cash, cash equivalents and restricted cash, and no debt. This includes net proceeds raised of $175 million raised through equity offerings and a total of $200 million in payments from partners Bristol Myers Squibb, Novo Nordisk and Roche.
As of February 11, 2022, Prothena had approximately 46.7 million ordinary shares outstanding.

2022 Financial Guidance

The Company expects the full year 2022 net cash used in operating and investing activities to be $120 to $132 million, which includes an expected $40 million clinical milestone payment from Novo Nordisk and expects to end the year with approximately $454 million in cash, cash equivalents and restricted cash (midpoint). The estimated full year 2022 net cash used in operating and investing activities is primarily driven by an estimated net loss of $154 to $170 million, which includes an estimated $32 million of non-cash share-based compensation expense.

Conference Call Details

Prothena management will discuss these results and its 2022 financial guidance during a live audio conference call today, Thursday, February 17, 2022, at 4:30 PM ET. The conference call will be made available on the Company’s website at www.prothena.com under the Investors tab in the Events and Presentations section. Following the live audio webcast, a replay will be available on the Company’s website for at least 90 days.

To access the call via dial-in, please dial (888) 440-6385 (U.S. and Canada toll free) or +00 1 646 960-0180 (international) five minutes prior to the start time and refer to conference ID number 92750. A

replay of the call will be available until March 3, 2022, via dial-in at (800) 770-2030 (U.S. toll free) or +00 1 647 362-9199 (international), Conference ID Number 92750.

On February 17, 2022 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported commencement of production of its first dendritic cell cancer vaccine for a compassionate use patient at its recently licensed production facility in Sawston, UK (Press release, Northwest Biotherapeutics, FEB 17, 2022, View Source [SID1234608257]).

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This milestone follows approval by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) of a license for manufacture of GMP (clinical grade) cell therapy products at its Sawston, UK facility for compassionate use cases, and approval by the Human Tissue Authority (HTA) of a license for collection and processing of human cells and tissues for medical purposes. Under this regulatory program in the UK, the vaccine is identified as ADCV ("Autologous Dendritic Cell Vaccine").

As previously reported, the MHRA license was received in December of 2021, following nearly two years of preparations. This included hiring and training of technical staff, preparation of approximately 1,000 regulatory documents (including Standard Operating Procedure documents and others), validation of facilities, equipment and protocols, and practice manufacturing cycles. This was followed by a review and detailed inspection by the MHRA.

Since the issuance of the MHRA license, Advent Bioservices, NW Bio’s contract manufacturer in the UK, has been conducting the required post-approval re-validations and testing so that the facility is now ready for the manufacture of cell therapy products for clinical use. Accordingly, the first vaccine production for compassionate use treatment for a glioblastoma patient has now begun in the Sawston facility.

The Company anticipates that Phase 1A of the Sawston facility will have the capacity to produce cancer vaccines for 450-500 patients per year. The Company plans to continue developing the Sawston facility in phases, both to calibrate the capital expenditures with the capacity needed and to leave room for implementation of new technologies such as the Flaskworks system.

On February 17, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the Company will release its fourth quarter 2021 financial results on Thursday, February 24, 2022, after the close of U.S. markets (Press release, Curis, FEB 17, 2022, View Source,-2022 [SID1234608256]). Management will host a conference call on the same day at 4:30 pm ET.

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To access the live conference call, please dial (888) 346-6389 from the United States or (412) 317- 5252 from other locations, shortly before 4:30 pm ET. The conference call can also be accessed on the Curis website at www.curis.com in the ‘Investors’ section. A replay of the financial results conference call will be available on the Curis website shortly after completion of the call.

On February 17, 2022 College of American Pathologists (CAP) reported A new evidence-based guideline published can help improve how pediatric and adult patients with the most common type of primary brain tumor, diffuse glioma, are diagnosed and managed (Press release, College of American Pathologists, FEB 17, 2022, View Source [SID1234608254]).

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"Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas," published in an early online edition of Archives of Pathology & Laboratory Medicine, sets forth 13 recommendations to guide biomarker testing of these tumors. Diffuse gliomas affect approximately 15,000 people in the US each year and present with widely variable clinical courses and treatment approaches.

"Our understanding of diffuse gliomas as discrete genetic and clinical entities has advanced markedly in the last decade, making molecular testing an established component of their integrated diagnosis," explains guideline chair Daniel Brat, MD, PhD, FCAP. "This allows for a more refined definition of disease and better prediction of both prognosis and therapeutic response."

Traditionally, diffuse gliomas have been classified by their microscopic properties as astrocytomas, oligodendrogliomas, or oligoastrocytomas ranging from World Health Organization (WHO) grades 2 to 4. And while there is some standardization around molecular-level definitions and classifications, the molecular profiles and genetic alterations of diffuse gliomas can vary widely, as can the testing methods that pathologists use to assess them.

With the new CAP guideline, clinical teams now have evidence-based guidance for diffuse glioma molecular testing more broadly, which can help improve the diagnosis, prognosis, and therapeutic care for patients.

Working across the clinical spectrum, three societies collaborated with the CAP on the guideline: the Society for Neuro-Oncology, the American Association of Neuropathologists, and the Association for Molecular Pathology.

Most notably, the guideline recommendations:

Call for IDH mutation testing for all diffuse gliomas in the appropriate clinical and radiologic setting.
Address the use of tests that assess the status of several genetic alterations that allow pathologists to classify diffuse gliomas according to the WHO classification schema.
Offers guidance specific to biomarker testing in pediatric patients with diffuse gliomas.
Under Dr. Brat’s leadership, an expert panel screened more than 4,000 titles and abstracts, reviewed 703 manuscripts, and extracted data from 188 studies to develop the recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach—a common, transparent method for grading quality (or certainty) of evidence and strength of recommendations.

Consistent with the CAP’s guideline process and principles, which follow the National Academy of Medicine’s standards, the guideline will be reviewed in four years, or earlier if evidence becomes available that could potentially alter the original guideline recommendations.

On February 17, 2022 Repertoire Immune Medicines, Inc. reported it has entered a sponsored research agreement with UMass Chan Medical School (UMass Chan) to identify the specific T cell and antigen pairs involved in causing the onset and progression of the autoimmune disease vitiligo (Press release, Repertoire, FEB 17, 2022, View Source [SID1234608253]). The potential discovery of these immunogenic drivers of vitiligo could be used to develop antigen-specific therapeutic candidates for this disease.

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The research team at UMass Chan will be led by John E. Harris, M.D., Ph.D., Chair and Professor of Dermatology and Director of the Vitiligo Clinic and Research Center.

"In autoimmune diseases, the best therapeutic options typically act broadly to suppress the immune system, which can lead to other complications for patients. One of the challenges to discovering new treatment options for vitiligo is the significant complexity of the immune system," said Dr. Harris. "We understand the role of the T cell but have not been able to identify the specific codes directing their function. The opportunity to combine our expertise in vitiligo with Repertoire’s DECODE technology means that, for the first time, we may be able to advance from translational insight to novel, antigen-specific therapies."

Vitiligo is a chronic autoimmune disease in which CD8+ T cells kill melanin-producing cells, leading to the loss of skin pigmentation. In autoimmune diseases like vitiligo, the immune system directs T cells to target and damage healthy cells. It is unknown exactly why this occurs, but it is understood that the immune system activates T cells through codes communicated by antigens that direct T cell activity. If the codes directing the CD8+ T cells can be identified, then it may be possible to develop an immunotherapy that targets these cells and prevents them from killing healthy cells.

"The deep expertise and clinical experience that the UMass Chan team has in the field of vitiligo makes this an ideal partnership for Repertoire. We will be able to apply the proprietary technology in our DECODE platform to assess and potentially identify the key drivers of the dysregulated immune response underlying this autoimmune disease, specifically the T cells and the antigens that activate them," said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. "Repertoire’s DECODE technology also provides us with the potential to design targeted immunotherapies for vitiligo."

About the DECODE Platform

The DECODE platform is a powerful discovery engine that characterizes essential elements of the immune synapse. In particular, the platform identifies T cell receptor-antigen pairs in the context of other important features of the immune synapse, such as T cell function and how these antigens are presented by molecules on antigen-presenting cells, known as major human leukocyte antigen, or HLA, molecules. Repertoire intends to utilize these insights into key drivers that govern immune function to design and develop novel immune product candidates.