On January 11, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported 2022 corporate priorities and anticipated clinical development and research milestones (Press release, Xencor, JAN 11, 2022, View Source [SID1234598571]).

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"The plug-and-play nature of Xencor’s XmAb Fc domains and our protein engineering expertise have enabled a broad portfolio of bispecific antibody and engineered cytokine drug candidates, as well as a multitude of partnerships, which have thus far produced three marketed products," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "In 2022, we expect emerging clinical data to continue to support our own mid-stage development plans for vudalimab and plamotamab, and we will continue to initiate new studies with potential to present new data that may define a path to registration for these programs. Additionally, we remain excited by the opportunities to use our technological competitive advantage to address challenging areas of biology and continually grow our portfolio, now with multiple reduced-potency cytokines and CD3 and CD28 T cell engagers in development, both internally at Xencor and with our partners."

Execute on development plans for mid-stage XmAb bispecific antibody programs

Vudalimab (PD-1 x CTLA-4), designed to activate intra-tumoral T cells
Xencor presented updated Phase 1 expansion cohort data in November 2021 and is enrolling a Phase 2 study in patients with metastatic castration-resistant prostate cancer (mCRPC), where vudalimab is being evaluated as a monotherapy or in combination depending on the tumor’s molecular subtype. Xencor plans to:

Initiate a second Phase 2 study, evaluating vudalimab in patients with advanced pelvic tumors, including clinically defined high-risk mCRPC and certain gynecologic malignancies.
Present initial data from the Phase 2 study in mCRPC, in the second half of 2022.
Plamotamab (CD20 x CD3), for B-cell malignancies
Xencor presented updated Phase 1 dose-escalation data in December 2021 and is currently recruiting non-Hodgkin lymphoma patients in expansion cohorts of plamotamab monotherapy at the Phase 2 recommended dose. Xencor entered a global collaboration and license agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to expand the Company’s strategy to develop plamotamab as part of multiple highly active chemotherapy-free regimens across B-cell cancers. Xencor plans to:

Initiate potentially registration-enabling Phase 2 study, evaluating plamotamab in combination with tafasitamab and lenalidomide, in patients with relapsed or refractory DLBCL.
Incorporate subcutaneous administration into the ongoing Phase 1 monotherapy study.
Present data from Phase 1 expansion cohorts, in the second half of 2022.
Develop B-cell targeted CD28 bispecific antibodies to selectively enhance T-cell cytotoxic activity in combination with plamotamab.
Advance multiple potency-reduced XmAb cytokine programs in oncology and autoimmune disease

Xencor’s engineered, potency-reduced cytokines are designed to expand select immune cell populations, to have longer circulating half-life and to be tolerable, active and easy to administer. XmAb cytokines incorporate Xtend extended half-life technology.

XmAb306, potency-reduced IL15/IL15Rα-Fc fusion protein
Recently, Xencor announced encouraging initial dose-escalation data from an ongoing Phase 1 study in patients with advanced solid tumors, in which the preliminary safety profile, biological activity and signs of anti-tumor activity provide initial validation for the Company’s approach to engineering cytokine therapeutics. Xencor plans to:

Announce new clinical studies of XmAb306 in combination with other agents, such as NK- or T-cell recruiting therapies in collaboration with the Company’s co-development partner.
XmAb564, potency-reduced IL2-Fc fusion targeting regulatory T cells in autoimmune disease
Xencor plans to:

Present tolerability, durability and biomarker data from the ongoing Phase 1 single-ascending dose study in healthy volunteers.
Identify development indications and initiate a multiple-ascending dose study in select patient populations.
XmAb662, potency-reduced IL12-Fc fusion protein designed to increase tumor immunogenicity
Xencor plans to:

Submit an investigational new drug (IND) application in 2022, and initiate a Phase 1 study in patients with advanced solid tumors in 2023.
Xencor plans to present preclinical data from additional cytokine-Fc programs in 2022.

Expand the Company’s portfolio with the first internally developed XmAb 2+1 CD3 and XmAb CD28 bispecific antibodies advancing into Phase 1 clinical studies

XmAb819 (ENPP3 x CD3), XmAb 2+1 bispecific antibody for renal cell carcinoma (RCC)
The multivalent XmAb 2+1 bispecific antibody format enables greater selectivity for tumor cells compared to normal cells, which also express ENPP3 at lower levels. Xencor plans to:

Initiate a Phase 1 study evaluating XmAb819 in patients with RCC in the first half of 2022.
XmAb808 (B7-H3 x CD28), tumor-selective, co-stimulatory CD28 bispecific antibody
CD28 is a key immune co-stimulatory receptor on T cells; however, the ligands that activate T cells through CD28 are usually not expressed on tumor cells. Targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells, for example, to T cells recognizing neoantigens or in concert with CD3 T-cell engaging bispecific antibodies. XmAb808 targets the broadly expressed tumor antigen B7-H3. Xencor plans to:

Submit an IND application in the first half of 2022, and initiate a Phase 1 study in patients with advanced solid tumors in the second half of 2022.
Cash Position and Financial Guidance

Xencor ended the fourth quarter of 2021 with unaudited cash, cash equivalents, receivables and marketable debt securities totaling approximately $660 million. Based on current operating plans, Xencor expects to have sufficient cash resources to fund research and development programs and operations through 2025.

On January 11, 2022 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported updated data from the Company’s ongoing Phase 1/2 study evaluating ADXS-503 in combination with KEYTRUDA (Press release, Advaxis, JAN 11, 2022, View Source [SID1234598570]). ADXS-503 is the first drug construct from the ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens.

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"NSCLC patients resistant to PD-1/-L1 checkpoint inhibitors (CPIs) have limited treatment options. Current treatment guidelines allow for CPI re-challenge but the overall response rate (ORR) seen with this approach is below 10% and disease control rate (DCR) of up to 45%. Thus, it is encouraging to report that in Part B of the study, the documented ORR has now increased to 15.4 % and DCR has reached 46% in the first 13 evaluable patients treated with ADXS-503 as an add-on therapy at progression with pembrolizumab," said Dr. Jonathan W. Goldman, Associate Professor of UCLA Hematology and Oncology, Associate Director of Drug Development and Director of Clinical Trials in Thoracic Oncology at UCLA Medical Center in Santa Monica, California. "These results now include a second additional patient with a partial response and 4 patients with stable disease. The durable nature of disease control is also encouraging and includes two patients with ongoing partial responses for 702 and 189 days, and three patients with stable disease sustained for 448, 175 and 117 days."

Dr. Goldman continued, "If the addition of ADXS-503 to patients progressing on pembrolizumab could achieve a durable response rate at or above 20%, with minimal added toxicity, this combination could become a new therapeutic option for this underserved patient population. We look forward to completing the enrollment of a total of 18 patients in Stage 1 of Part B."

Dr. Andres A. Gutierrez, Chief Medical Officer of Advaxis, said, "The enrollment of Part C of the study, evaluating NSCLC patients treated in first line with ADXS-503 in combination with pembrolizumab, has also started. Given the median progression free survival (PFS) achieved with CPIs alone in first line NSCLC is 7-10 months, and the encouraging results from Part B in this study, it is expected that the addition of ADXS-503 to pembrolizumab may achieve meaningful improvements in PFS above standard of care with a target of greater than or equal to 9 months. Three patients have thus far been evaluated showing a disease control rate of 67%, with two patients sustaining stable disease for 332 and 94 days. As expected, the combination therapy has been well tolerated with mild and transient flu-like syndrome a few hours after the infusion of the drugs but without increasing the frequency of immune-related adverse events."

Ken Berlin, Chief Executive Officer of Advaxis, said, "Major milestones for the ADXS-503 trial in the second half of 2022 include updated clinical and immunogenicity data for all patients in Stage 1 in Part B and from up to 10 patients in Part C. Also, initial clinical and immunogenicity data from the ADXS-504 trial in early prostate cancer are expected to be reported in the second half of this year."

Key Updates and Future Data Read-outs:

In Part B of the study, 14 patients have been treated and 13 are evaluable with ADXS-503 as an add on therapy to patients failing pembrolizumab as last therapy with all of them evaluable for safety and efficacy
Combination therapy was well tolerated with no dose-limiting-toxicity (DLT) or added toxicity of the two drugs. Grade 1 and 2, transient and reversible events included chills, fever, fatigue, in approximately half of the patients
The ORR was 15.4% (2/13) and DCR was 46% (6/13)
Clinical benefit was durable, with two partial responses (PR) sustained for 702 and 189 days, respectively, and 3 patients with stable disease (SD), sustained for 448, 175 and 117 days. Another patient with stable disease is still under evaluation
Available data demonstrate that patients who achieve clinical benefit include those with PD-L1 expression ≥50%, secondary resistance disease to pembrolizumab and those who show proliferation and/or activation of NK and CD8+ T cells within the first weeks of therapy
Additional translational studies, including flow cytometry, ELISPOT, cytokines/chemokine levels, mutational analysis, MSI TMB and cfDNA and their clinical correlates, will be presented at an upcoming medical meeting
In Part C of the study, 3 patients with newly diagnosed NSCLC have been treated with ADXS-503 plus pembrolizumab. Treatment has been well tolerated and disease control rate thus far is 67%, with two patients sustaining stable disease for 332 and 94 days.
Enrollment in Part B and Part C of the ongoing study will continue to further evaluate the clinical benefit and immune effects of adding on ADXS-503 to patients progressing on pembrolizumab
The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. The two dose levels with monotherapy in Part A, (1 X108 and 5 X108 CFU) have been completed. Part B with ADXS-503 (1 X108 CFU) in combination with KEYTRUDA is currently enrolling its efficacy expansion for up to 18 patients at dose level 1 (1 X108 CFU + KEYTRUDA) with the potential to proceed to dose level 2 (5 X108 CFU + KEYTRUDA) at a later date. Part C of this ADXS-503 trial evaluating ADXS-503 in combination with KEYTRUDA (1 X108 CFU + KEYTRUDA) as a first line treatment for patients with NSCLC with PD-L1 expression ≥ 1% or who are unfit for chemotherapy, is currently enrolling patients.

About ADXS-503
ADXS-503 is a live attenuated Listeria monocytogenes (Lm)-based, off-the-shelf immunotherapy that is under clinical development as a single agent and in combination with other cancer therapies for the treatment of squamous and non-squamous non-small cell lung cancer (NSCLC). ADXS-503 is bioengineered to secrete an antigen-adjuvant fusion protein consisting of a truncated fragment of listeriolysin O (tLLO) fused to 22 NSCLC-associated tumor antigens. The proposed mechanism of action of Advaxis’ Lm-based immunotherapy is to stimulate both the innate and adaptive immune systems to initiate a coordinated antitumor response culminating in the generation of tumor antigen-specific T cells that are capable of infiltrating and destroying the tumor.

On January 11, 2022 Amgen (NASDAQ:AMGN) and Arrakis Therapeutics reported a research collaboration focused on the discovery and development of RNA degrader therapeutics against a range of difficult-to-drug targets in multiple therapeutic areas (Press release, Amgen, JAN 11, 2022, https://www.prnewswire.com/news-releases/amgen-and-arrakis-therapeutics-announce-multi-target-collaboration-to-identify-novel-rna-degrader-small-molecule-therapeutics-301458380.html [SID1234598569]). This new class of "targeted RNA degraders" consists of small molecule drugs that selectively destroy RNAs encoding disease-causing proteins by inducing their proximity to nucleases.

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Under the terms of the agreement, Arrakis will lead research activities for the identification of RNA-targeted small molecule (rSM) binders against a broad set of targets nominated by Amgen. Both parties will collaboratively design and functionalize these molecules to specifically degrade targeted RNAs, and Amgen will lead further preclinical and clinical development activities. Amgen will pay $75 million upfront to Arrakis for five initial programs and will have the option to nominate additional programs. For each program, Arrakis will be eligible for additional payments from Amgen for preclinical, clinical, regulatory and sales milestones, and royalties up to low double digits. Arrakis could potentially receive several billion dollars in future payments if all milestones are met and future program options are exercised.

"Targeted RNA degradation is an exciting area that is pushing the boundaries of drug discovery and design," said Raymond Deshaies, Ph.D., senior vice president of Global Research at Amgen. "The collaboration with Arrakis combines Amgen’s induced proximity expertise in discovering multispecific molecules to target the biologic mechanisms of disease and Arrakis’ pioneering discovery platform to predict RNA structures and identify small molecules that bind to them, significantly broadening the possibilities of addressing difficult protein targets considered undruggable because they may not have binding sites needed for conventional medicines. Combining this approach with Amgen’s targeted protein degradation induced proximity research already underway has the potential to significantly expand the druggable genome."

By integrating the capabilities of the two innovative discovery platforms from Amgen and Arrakis, the collaboration creates an opportunity to design and engineer targeted RNA degraders. Amgen has built its Induced Proximity Platform to identify multispecific molecules that harness the power of cell biology by forming novel connections between natural effectors and targets. One end of the molecule binds to the target to be altered (inhibited, activated or destroyed) and the other end binds to a cellular effector that acts on the target, offering the potential to engage a broad range of cellular mechanisms to treat disease. With targeted RNA degraders, the effector, such as a ribonuclease or other RNA modulator, is brought into proximity of the RNA to degrade or otherwise modify the disease-causing RNA of interest. This complements Amgen’s existing efforts to target RNA with siRNA. In this collaboration, Arrakis’ rSM platform will be applied as a drug discovery engine to identify small molecules that bind target RNA. These rSMs will then be functionalized with nuclease recruiters to create heterobifunctional molecules that trigger degradation of disease-relevant RNA targets.

"We are excited to partner with Amgen’s strong research team to pursue a shared goal of creating a new class of medicines that induce degradation of disease-causing RNAs. This collaboration further demonstrates the utility of our proprietary rSM discovery platform for targeting RNA with small molecules and paves the way for creating powerful new treatments for patients," said Michael Gilman, Ph.D., chief executive officer of Arrakis. "Based on our long-term goal to build a broad and industry-leading platform that adapts state-of-the-art drug discovery tools to target RNA biology, we have enabled a range of different applications and collaborations to leverage our science, a strong capital position and the ability to grow our business and our impact to advance RNA-targeted drug programs for diseases unaddressed by today’s medicines."

On January 11, 2022, Harpoon Therapeutics, Inc. (the "Company") Presented the Corporate Presentation (Presentation, Harpoon Therapeutics, JAN 11, 2022, View Source [SID1234598564]).

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On January 11, 2022 GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) reported that the US Government will purchase an additional 600,000 doses of sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, enabling further nationwide access to sotrovimab for patients (Press release, GlaxoSmithKline, JAN 11, 2022, View Source [SID1234598563]). The additional 600,000 doses will be delivered throughout the first quarter of 2022. This agreement is an amendment to earlier commitments announced with the US Government in November 2021.

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Including the commitments announced today, GSK and Vir have received binding agreements for the sale of approximately 1.7 million doses of sotrovimab worldwide. In addition, today’s agreement also includes the option for the US government to purchase further additional doses in the second quarter of 2022.

Sotrovimab, which was granted Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) in May 2021, is an investigational single-dose intravenous (IV) infusion SARS-CoV-2 monoclonal antibody. Under the EUA, sotrovimab can be used for the treatment of mild-to-moderate COVID-19 in adults and paediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalisation or death.

GSK and Vir expect to manufacture approximately 2 million doses globally in the first half of 2022 and additional doses in the second half of the year.

Maya Martinez-Davis, President, US Pharmaceuticals, GSK, said: "We are proud to continue to work with the US government to bring sotrovimab to patients who need it, especially as the Omicron variant continues to grow in prevalence across the country. We understand the role we can play in supporting the ongoing pandemic response, and our teams are working with urgency to explore options to expand our supply capacity so we can support more patients in 2022."

George Scangos, PhD, chief executive officer of Vir, said: "As the Omicron variant continues its rapid spread alongside the still prevalent Delta variant, we are pleased to once again work with the US government to provide more access to sotrovimab for people in the US at high risk of progression to severe COVID-19. Data from multiple pseudo-virus and live virus preclinical studies, generated by industry and academia, continue to demonstrate that sotrovimab retains activity against all tested variants of concern and interest. We are proud of our ongoing contributions to the fight against the COVID-19 pandemic here in the US and around the world."

The Biomedical Advanced Research and Development Authority (BARDA), part of the Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR), collaborated with the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) and Army Contracting Command to purchase contract numbers W58P0521C0008 and W58P0522C0002.

In June 2021, GSK and Vir announced confirmatory full results for the COMET-ICE Phase III trial examining use of sotrovimab for early treatment of mild-to-moderate COVID-19 in high-risk, non-hospitalised adults. The trial met the primary endpoint with a 79% reduction (adjusted relative risk reduction) (p<0.001) in all-cause hospitalisations for more than 24 hours or death due to any cause by Day 29 compared to placebo. In absolute numbers, 30 (6%) of the 529 patients in the placebo arm progressed, compared to six (1%) of the 528 patients receiving sotrovimab. In clinical trials conducted to date, sotrovimab has been well-tolerated. The most common adverse reactions are hypersensitivity and infusion-related reactions, seen in approximately 2% and 1% of cases, respectively.

GSK and Vir are committed to the ongoing evaluation of sotrovimab as the COVID-19 landscape continues to evolve at different rates across the globe and new variants of concern and interest emerge. Preclinical pseudo-virus data, published in bioRxiv, demonstrate that sotrovimab retains activity against all tested variants of concern and interest of the SARS-CoV-2 virus as defined by the World Health Organization, including, but not limited to, Omicron (B.1.1.529), Delta (B.1.617.2), Delta Plus (AY.1 or AY.2) and Mu (B.1.621). Preclinical live virus testing has also been completed with data, recently published in bioRxiv, further demonstrating that sotrovimab retains activity against the Omicron variant.

About sotrovimab
Sotrovimab is an investigational SARS-CoV-2 neutralising monoclonal antibody. The antibody binds to an epitope on SARS-CoV-2 shared with SARS-CoV-1 (the virus that causes SARS), indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. Sotrovimab, which incorporates Xencor, Inc.’s Xtend technology, has also been designed to achieve high concentration in the lungs to ensure optimal penetration into airway tissues affected by SARS-CoV-2 and to have an extended half-life.

About global access to sotrovimab
Sotrovimab is authorised for emergency use in the US and has been granted a marketing authorisation in the EU, conditional marketing authorisation in Great Britain, provisional marketing authorisation in Australia, and conditional marketing authorisation in Saudi Arabia. It has also been approved via Japan’s Special Approval for Emergency Pathway. Temporary authorisations for sotrovimab have also been granted in 12 other countries.

Sotrovimab is supplied in several countries worldwide, including through national agreements in the US, UK, Japan, Australia, Canada, Singapore, Switzerland, and the United Arab Emirates. The companies are also supplying sotrovimab to participating Member States of the EU through a Joint Procurement Agreement with the European Commission. Additional agreements are yet to be disclosed due to confidentiality or regulatory requirements.

Sotrovimab in the United States
The following is a summary of information for sotrovimab. Healthcare providers in the US should review the Fact Sheets for information about the authorized use of sotrovimab and mandatory requirements of the EUA. Please see the Food and Drug Administration (FDA) Letter of Authorization, full Fact Sheet for Healthcare Providers and full Fact Sheet for Patients, Parents, and Caregivers.

Sotrovimab has been authorized by the US FDA for the emergency use described below. Sotrovimab is not FDA-approved for this use.

Sotrovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of sotrovimab under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Authorized Use
The US FDA has issued an EUA to permit the emergency use of the unapproved product sotrovimab for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Limitations of Authorized Use
Sotrovimab is not authorized for use in patients:

who are hospitalized due to COVID-19, OR
who require oxygen therapy due to COVID-19, OR
who require an increase in baseline oxygen flow rate due to COVID-19 (in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity)
Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID19 requiring high flow oxygen or mechanical ventilation.

Important Safety Information

CONTRAINDICATIONS
Sotrovimab is contraindicated in patients who have a history of anaphylaxis to sotrovimab or to any of the excipients in the formulation.

WARNINGS AND PRECAUTIONS
There are limited clinical data available for sotrovimab. Serious and unexpected adverse events may occur that have not been previously reported with sotrovimab use.

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions
Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening.

Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (eg, pre-syncope, syncope), dizziness and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs.

Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.

Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration
Clinical worsening of COVID‑19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, tachycardia, bradycardia), fatigue and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID‑19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID‑19
Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID‑19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID‑19 requiring high flow oxygen or mechanical ventilation. Therefore, sotrovimab is not authorized for use in patients: who are hospitalized due to COVID‑19, OR who require oxygen therapy due to COVID‑19 OR who require an increase in baseline oxygen flow rate due to COVID‑19 in those on chronic oxygen therapy due to underlying non‑COVID‑19 related comorbidity.

ADVERSE EVENTS
Hypersensitivity adverse reactions have been observed in 2% of patients treated with sotrovimab and 1% with placebo in COMET-ICE.

The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo.

USE IN SPECIFIC POPULATIONS
Pregnancy
There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcome. Sotrovimab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Lactation
There are no available data on the presence of sotrovimab in human milk, the effects on the breastfed infant or the effects on milk production. Individuals with COVID-19 who are breastfeeding should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

About the GSK and Vir collaboration
In April 2020, GSK and Vir entered into a collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. The collaboration uses Vir’s proprietary monoclonal antibody platform technology to accelerate existing and identify new anti-viral antibodies that could be used as therapeutic or preventive options to help address the current COVID-19 pandemic and future outbreaks. The companies will leverage GSK’s expertise in functional genomics and combine their capabilities in CRISPR screening and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. They will also apply their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.

GSK commitment to tackling COVID-19
GSK’s response to COVID-19 has been one of the broadest in the industry, with potential treatments in addition to the Company’s vaccine candidates in development with partner organisations.

GSK is collaborating with several organisations on COVID-19 vaccines by providing access to its adjuvant technology. The Company is working with Sanofi SA, Medicago Inc. and SK bioscience Co., Ltd. to develop adjuvanted, protein-based vaccine candidates, and all are now in phase III clinical trials. The use of an adjuvant can be of particular importance in a pandemic since it may reduce the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and contributing to protecting more people in need.

GSK is also working with mRNA specialist CureVac NV to jointly develop next-generation, optimised mRNA vaccines for COVID-19 with the potential to address multiple emerging variants in one vaccine.

GSK is also exploring treatments for COVID-19 patients, collaborating with Vir Biotechnology to investigate monoclonal antibodies that could be used as therapeutic or preventive options for COVID-19.

Vir’s commitment to COVID-19
Vir was founded with the mission of addressing the world’s most serious infectious diseases. In 2020, Vir responded rapidly to the COVID-19 pandemic by leveraging our unique scientific insights and industry-leading antibody platform to explore multiple monoclonal antibodies as potential therapeutic or preventive options for COVID-19. Sotrovimab is the first SARS-CoV-2-targeting antibody Vir advanced into the clinic. It was carefully selected for its demonstrated promise in preclinical research, including an anticipated high barrier to resistance and potential ability to both block the virus from entering healthy cells and clear infected cells. Vir is continuing to pursue novel therapeutic and prophylactic solutions to combat SARS-CoV-2 and future coronavirus pandemics, both independently and in collaboration with its partners.