On March 25, 2022 Bristol-Myers Squibb K.K. reported that the Ministry of Health, Labour and Welfare (MHLW) has accepted the supplemental New Drug Application for Breyanzi (lisocabtagene maraleucel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy for the second-line treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (Press release, Bristol-Myers Squibb, MAR 25, 2022, View Source [SID1234610988]). This is the first CAR T cell therapy application filed for the second-line treatment of R/R LBCL in Japan.

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!

The acceptance is based on the efficacy and safety data yielded by the TRANSFORM study in patients with R/R aggressive B-cell non-Hodgkin lymphoma conducted in Japan, the U.S. and the EU, and other studies.

LBCL comprises several disease types including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin lymphoma in Japan, accounting for 30-40% of all B-cell cases diagnosed,1 and is especially prevalent among those in their 60s.2 There are currently no established standard-of-care treatment options for patients with R/R LBCL,3 which underscores the need for new treatments for this disease.

Makoto Sugita, Vice President, R&D Japan, Bristol-Myers Squibb K.K., commented, "I am pleased we are the first company in Japan to file an application for a cell therapy in second-line relapsed or refractory large B-cell lymphoma. This filing brings us one step closer to delivering a potentially practice-changing treatment for primary relapsed or refractory large B-cell lymphoma, making Breyanzi available to more patients in need, and underscores the advancements we’re making in cell therapy research to transform the lives of patients with difficult-to-treat blood cancers, including lymphoma."

Breyanzi is a CD19-directed CAR T cell therapy with a defined composition and 4-1BB costimulatory domain. Breyanzi is administered as a defined composition to reduce variability of the CD8 and CD4 component dose. The 4-1BB signaling domain enhances the expansion and persistence of the CAR T cells. Breyanzi has been designated as an orphan regenerative medicine product by the MHLW for aggressive B-cell non-Hodgkin lymphoma, and was approved in March 2021 for the treatment of patients with R/R LBCL and R/R follicular lymphoma. 4,5

Breyanzi U.S. FDA-Approved Indication

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients.

Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com or contact Bristol Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

On March 25, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorisation of ciltacabtagene autoleucel (cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy (Press release, Johnson & Johnson, MAR 25, 2022, View Source [SID1234611004]). In December 2017, Janssen Biotech, Inc. (Janssen) entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialise cilta-cel.1

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!

Cilta-cel is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies.2 CAR-T therapy is a highly personalised technology where a patient’s own T-cells are re-programmed to target and kill cancer cells – and is administered as a single infusion.3

Multiple myeloma is an incurable blood cancer, with around 50 percent of newly diagnosed patients not reaching five-year survival.4,5 Despite the development of additional treatment options in recent years, most people living with multiple myeloma face poor prognoses after being exposed to all three major drug classes, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.6

"Although significant advances have been made in the treatment of multiple myeloma, it remains a heterogenous disease that is challenging to treat," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "Therapeutic innovations with novel mechanisms of action are urgently needed. Our focus is on bringing transformative treatments to the medical community, like cilta-cel, for patients with multiple myeloma in need of new options."

The positive CHMP Opinion is supported by data from the pivotal CARTITUDE-1 study. Results from the study were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting (Abstract #549).2

"At Janssen, we are resolute in our commitment to advance science and improve outcomes for patients diagnosed with multiple myeloma," said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Research, Janssen Research & Development, LLC. "Today’s CHMP positive opinion marks important progress in the ongoing clinical development and registration of cilta-cel, globally."

This CHMP Opinion follows the recent approval of cilta-cel by the United States (U.S.) Food and Drug Administration (FDA) in February 2022.

#ENDS#

About Ciltacabtagene Autoleucel (cilta-cel)
Cilta-cel is a B-cell maturation antigen (BCMA)-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA.2,3 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.7,8 The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. 1 Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.9

In December 2017, Janssen Biotech, Inc. (Janssen) entered into an exclusive worldwide license and collaboration agreement with Legend Biotech to develop and commercialise cilta-cel.1

In April 2021, Janssen announced its submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed and/or refractory multiple myeloma. In addition to United States (U.S.) Breakthrough Therapy Designation granted in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission (EC) in April 2019, and a Breakthrough Therapy Designation in China in August 2020. Janssen also received Orphan Drug Designation for cilta-cel from the EC in February 2020 and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020.

About Multiple Myeloma
Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4,10 When damaged, these plasma cells change and grow out of control.10 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.11 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.12

On March 25, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported its financial results for the year ended December 31, 2021 (Press release, Moleculin, MAR 25, 2022, View Source [SID1234610989]). The Company also provided an update on its portfolio of oncology drug candidates for the treatment of highly resistant tumors and viruses.

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!

"Over the course of 2021, we have made significant progress across multiple fronts. As we look ahead, I believe we are well positioned for an exciting 2022 with a number of clinical and regulatory milestones expected throughout the year," commented Walter Klemp, Chairman and CEO of Moleculin. "Our Annamycin development programs in STS lung mets and AML continue to progress and we remain encouraged by the data seen to date. Additionally, with the necessary regulatory approvals received, we are advancing parallel development of WP1122 for the treatment of COVID-19 and GBM. With our growing body of encouraging clinical data and our strong financing position, we remain laser focused on executing our initiatives, driving value for all stakeholders, and importantly, addressing unmet needs for people with highly resistant tumors and viruses."

Recent Highlights

●Appointed Joy Yan, M.D., Ph.D., an oncology physician-scientist with extensive experience in early and late clinical development with successful track record, to its Board of Directors.

●Successfully concluded the Company’s second Phase 1 trial (MB-105) in Poland evaluating Annamycin for the treatment of relapsed and refractory acute myeloid leukemia (AML), where Moleculin determined a dose of 240 mg/m2 as the Recommended Phase 2 Dose (RP2D) and demonstrated no signs of cardiotoxicity (a common problem with currently prescribed anthracyclines).

●Reported an updated independent safety review of certain preliminary data for the first 30 patients in its three Phase 1 clinical trials with Annamycin targeting relapsed or refractory AML and the metastases of soft tissue sarcoma to the lungs (STS Lung), which concluded there was no evidence of cardiotoxicity. The review included analysis of ejection fraction, echo strain and certain troponin levels intended to assess potential for both acute and chronic heart damage. Additionally, the Company reported evidence that Annamycin may have a substantially lower incidence of alopecia (hair loss) than currently prescribed anthracyclines such as doxorubicin.

●Reported preliminary interim results from its U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of STS lung metastases in its fourth cohort with three patients recruited and dosed which continues to document preliminary human activity for this drug. In this cohort one patient experienced a dose limiting toxicity (DLT) that resolved and continues in the trial. All three initial patients had their scans after two cycles and reported stable disease and are continuing in the study. This information is preliminary and subject to change.

●Received allowance from the U.S. Food and Drug Administration (FDA) for the Company’s Investigational New Drug (IND) application to study WP1122 for the treatment of GBM. With this IND now cleared, Moleculin plans to identify investigators interested in initiating a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.

●Filed an amended protocol with both the Riverside Ethics Committee and Medicines and Healthcare Products Regulatory Agency (MHRA) to commence a Phase 1a clinical trial of WP1122 in the United Kingdom; once approved, the internally funded trial is expected to begin in the first half of 2022.

Programs Update

Next Generation Anthracycline – Annamycin

Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin, as well as demonstrating the ability to avoid the multidrug resistance mechanisms that typically limit the efficacy of doxorubicin and other currently prescribed anthracyclines. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple human clinical trials, including ongoing trials for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases, and the Company believes that the use of Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently prescribed anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes it may have the potential to treat a number of additional indications.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of STS lung metastases, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia.

For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

Upcoming Milestones Expectations

●H1 2022: Initiate Phase 1/2 study in Europe for the treatment of AML evaluating combination therapy of Annamycin + Ara-C.

●H1 2022: Commencement of an investigator-funded, second Phase 1b/2 clinical trial of Annamycin in sarcoma lung metastases in Europe.

●H1 2022: Complete Phase 1b portion of ongoing Phase 1b/2 study of Annamycin for the treatment of sarcoma lung metastases in the US.

Metabolism/Glycosylation Inhibitor – WP1122

Moleculin has new compounds designed to target the roles of glycolysis and glycosylation in both cancer and viral diseases. The Company’s lead Metabolism/Glycosylation Inhibitor, WP1122, is a prodrug of 2-DG that appears to improve the drug-like properties of 2-DG by increasing its circulation time and improving tissue/organ distribution. Based on recently published research that has identified that 2-DG has antiviral potential against SARS-CoV-2 in vitro, Moleculin believes WP1122 has significant potential as a COVID-19 therapy. Its unique mechanism of action may also be well-suited for combinations that potentiate existing therapies, including checkpoint inhibitors.

The Company has received authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) to commence a Phase 1a clinical trial of WP1122 in the United Kingdom. The Company also received a favorable opinion from the London – Riverside Research Ethics Committee in the UK to begin the study, which is expected to be conducted at the Medicines Evaluation Unit in Manchester, United Kingdom. In early March 2022, the Company filed an amended protocol with both the Riverside Ethics Committee and the MHRA. The amendment updated the dilution of the oral solution to achieve full dissolution of WP1122. No risk/benefit to the study was affected because of this change. The Phase 1a study in healthy human volunteers will investigate the effects of a single ascending dose (SAD) and multiple days of ascending dosing (MAD) of WP1122 administered as an oral solution. Dose escalation will take place in sequential SAD cohorts, and MAD will start as soon as SAD has completed at least 3 dosing cohorts in which WP1122 is found to be safe and well-tolerated. This study in healthy volunteers will explore safety and pharmacokinetics (PK), and subsequent clinical development will be in patients infected with SARS-CoV-2 to further evaluate safety and establish a favorable risk/benefit profile. The Company expects to enroll approximately 80 healthy volunteers in the United Kingdom.

Glioblastoma Multiforme

Additionally, the Company recently announced that the FDA is allowing the Company’s Investigational New Drug (IND) application to study WP1122 for the treatment of GBM to go forward. With this IND now cleared, Moleculin plans to identify investigators who are interested in initiating a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.

Upcoming Milestones Expectations

●H1 2022: Commence Phase 1a study of WP1122 for the treatment of COVID-19 in the UK.

●H1 2022: Potential to launch Phase 2 pivotal study of WP1122 for the treatment of COVID-19 outside of the US.

●2022: Identify investigators interested in initiating a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.

●Ongoing preclinical development work in additional anti-viral indications such as HIV, Zika, and Dengue. Collaborations targeted for 2022.

Summary of Financial Results for the Full Year 2021

Research and development (R&D) expense was $14.4 million and $12.8 million for the year ended December 31, 2021 and 2020, respectively. The increase in R&D of $1.6 million is mainly related to increase in the number of internally funded clinical trials and overall clinical trial activity, and costs related to manufacturing of additional drug product.

General and administrative expense was $8.4 million and $6.8 million for the year ended December 31, 2021 and 2020, respectively. The increase of $1.6 million is mainly related to an increase in headcount, consulting and advisory fees, and an increase in our corporate insurance.

For the year ended December 31, 2021 and 2020, the Company incurred net losses of $15.9 million which included non-cash gains of $6.7 million on warrants in 2021 as compared to $2.3 million in the prior year and approximately $2.4 million of stock-based compensation expense in 2021 as compared to $1.7 million in 2020.

The Company ended the year with $70.9 million of cash. The Company believes that this cash is sufficient to meet its projected operating requirements, which include a forecasted increase over its current R&D rate of expenditures, into 2024.

On March 25, 2022 Broncus Medical (02216HK), Inc., developer of diagnostic and therapeutic technology for a variety of lung diseases, reported online publication in the Respirology journal of a global, multicenter study demonstrating the effectiveness of the company’s Archimedes Virtual Bronchoscopic Navigation (VBN) System in guiding the sampling of peripheral pulmonary lesions (Press release, Broncus Technologies, MAR 25, 2022, View Source [SID1234611005]).

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!

The prospective, single-arm, multicenter study of 104 patients studied biopsy yield (biopsy forceps and/or needle), sampling yield (including cytologic sampling) and diagnostic yield using the Archimedes System to guide bronchoscopic transparenchymal nodule access (BTPNA) and guided transbronchial needle aspiration (TBNA). The global study took place at:

U.S. – Beth Israel Deaconess Medical Center, Cancer Treatment Centers of America at Southwestern Regional Medical Center, Duke University, Houston Methodist Hospital, Temple University Hospital, University of Pennsylvania
China – The First Affiliated Hospital of Guangzhou Medical University, Shanghai Chest Hospital
Germany – ThoraxKlinik
Hong Kong – Hong Kong Sanatorium and Hospital
The study’s authors concluded that, "BTPNA and TBNA contribute to safe and effective sampling of peripheral pulmonary lesions. A relatively high biopsy yield was obtained independent of the presence or absence of a bronchus sign, and high sampling yield and diagnostic yield were obtained independent of location, lesion size and presence or absence of a broncus sign."

The Archimedes VBN System combines fused fluoroscopy, real-time bronchoscopy and virtual bronchoscopic navigation for 3D views and access to nodules anywhere in the lung, with the ability to avoid major blood vessels through vessel mapping. Archimedes uniquely enables BTPNA, a sampling method that enables a surgeon to precisely and quickly access a lesion via tunneling when the lesion is not adjacent to an airway.

The study showed that BTPNA enabled a sampling yield of 90.2 percent and a biopsy yield of 86.3 percent, while the sampling yield across both BTPNA and guided TBNA was 93.9 percent. This was achieved with a low pneumothorax rate of only 1.9 percent. The diagnostic yield from more than one-year follow-up across both procedures was 75.4 percent and 72.8 percent, respectively, on the high and low estimate. Sufficient histologic and/or cytologic samples were obtained in 107 of 124 lesions, resulting in a technical success rate of 86.3 percent.

"Despite new technologies to improve bronchoscopic diagnosis, their results are limited by their reliance on the presence of an airway leading to the lesion. The BTPNA approach using virtual bronchoscopic navigation is exciting as it is demonstrating the ability to achieve a very high biopsy yield no matter where the lesion is located, while avoiding blood vessels and minimizing the risk of pneumothorax," said Gerard Criner, MD, Chair and Professor, Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University and Director, Temple Lung Center. "Seeing these results in a global multicenter study in a real world setting is very encouraging as we look to advance the care we can provide every day to lung cancer patients."

"In this study, BTPNA showed a superior biopsy yield when compared to today’s bronchoscopic diagnostic approaches. While BTPNA is an emerging approach, its capabilities will become even more valuable with the advent of new therapeutics in the near future, when both diagnosis and treatment will be able to be accomplished bronchoscopically, no matter where the lesion is located in the lung," said Brandon Markle, Senior Director of Global Sales and Marketing, Broncus Medical.

On March 25, 2022 Vaccitech plc (NASDAQ: VACC) reported its financial results for the full year ended December 31, 2021 and provided an overview of the Company’s recent corporate developments (Press release, Vaccitech, MAR 25, 2022, View Source [SID1234610991]). Vaccitech is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases and cancer.

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!

"2021 was a pivotal year for Vaccitech during which we achieved a number of strategic, operational, and financial objectives, advanced multiple immunotherapeutic and prophylactic candidates in clinical development and strengthened and expanded our T cell activating discovery engine platform via the acquisition of Avidea Technologies," commented Bill Enright, Vaccitech’s CEO. "All of this progress puts us in a strong position to deliver on our long-term plans. We anticipate that 2022 will be a year where we continue to advance our product pipeline with key data readouts in several programs. We look forward to reporting on these developments throughout the year."

2021 and Recent Corporate Developments

·Raised $166.5 million of proceeds in a Series B private financing, including $41.2 million from previously issued convertible loan notes that converted into Series B shares.
·Completed a public listing on NASDAQ, raising gross proceeds of $110.5 million through an offering of American Depository Shares.
·Initiated patient dosing in HPV001, a Phase 1/2 clinical trial of VTP-200, an immunotherapeutic candidate in development for the treatment of persistent infection with high-risk HPV.
·Signed a clinical trial collaboration agreement with Arbutus Biopharma Corporation to evaluate an innovative therapeutic combination for the treatment of patients with chronic Hepatitis B virus (HBV) infection who are already receiving standard-of-care nucleos(t)ide reverse transcriptase inhibitor, or Nrtl, therapy. The Phase 2a clinical trial will evaluate the safety, pharmacokinetics, immunogenicity, and antiviral activity of Arbutus’s RNAi therapeutic, AB-729, followed by Vaccitech’s immunotherapy candidate, VTP-300, in Nrtl-suppressed patients with chronic HBV infection.
·Signed a lease for 31,000 square feet within the Zeus development at Harwell Science and Innovation Campus in Oxfordshire, United Kingdom. The site will house Vaccitech’s headquarters, state-of-the-art wet laboratory, and offices. Vaccitech anticipates completing the relocation by mid-2022.
·Online publication in The Lancet Microbe results of a Phase 1 clinical trial of VTP-500, a vaccine candidate in development to prevent Middle East Respiratory Syndrome (MERS). The study, sponsored and conducted by researchers at The King Abdullah International Medical Research Centre in Saudi Arabia in partnership with Oxford University, showed that the vaccine candidate was generally well tolerated and induced both humoral and cellular immune responses.

·Presented at the AASLD The Liver Meeting data from a Phase 1 (HBV001) and Groups 1 and 2 of a Phase 1/2a (HBV002) clinical trial demonstrating that VTP-300 was tolerated and induced T cells against targeted HBV antigens in both healthy volunteers and patients with chronic HBV infection.
·Reported efficacy data from an interim analysis of the HBV002 clinical trial of VTP-300 in patients with chronic HBV infection. The data from 27 patients who completed three months in the trial demonstrated reductions in surface antigen (HbsAg) levels in patients receiving VTP300 both alone and in combination with nivolumab.
·Acquired Avidea Technologies, Inc. in a cash and stock transaction that added complementary synthetic T cell boosting technologies and expands Vaccitech’s pipeline to include autoimmunity to its current infectious disease and oncology therapeutic areas of focus. The transaction also furthers Vaccitech’s scientific expertise and establishes U.S.-based research and development capabilities.
·Cancer Research UK and the Ludwig Institute for Cancer Research initiated patient dosing in a Phase 1/2a clinical trial to test the safety and initial efficacy of VTP-600, an immunotherapeutic candidate in development for the treatment of non-small cell lung cancer. The therapeutic candidate employs Vaccitech’s viral vector prime-boost platform to induce T cell immunity against two cancer-associated proteins, MAGE-A3 and NY-ESO-1, found on some tumor cells.

Upcoming Milestones

·In the second quarter of 2022, the Company expects to present additional Phase 1/2a interim efficacy data of VTP-300 in patients with chronic HBV infection at the International Liver Congress on June 22 to 26, 2022, which is also expected to be followed by Phase 1/2a full efficacy clinical trial data in the second half of this year.
·In the third quarter of 2022, the Company expects to initiate dosing in a Phase 1/2 clinical trial of VTP-850 in patients with prostate cancer and also expects to initiate dosing of a Phase 2 clinical trial of VTP-300 in patients with chronic HBV infection.
·In the fourth quarter of 2022, the Company intends to conduct an interim efficacy review of HPV001, a Phase 1/2a clinical trial of VTP-200, a potential non-invasive treatment for low grade HPV-related cervical lesions.

Full Year 2021 Financial Highlights:

·Cash position: As of December 31, 2021, cash and cash equivalents were $214.1 million, compared to $43.3 million as of December 31, 2020. The increase was primarily due to completion of the Series B financing in the first quarter of 2021, which raised gross proceeds of $125.2 million, and to the initial public offering in the second quarter, which raised gross proceeds of $110.5 million. The Company believes its cash and cash equivalents are sufficient to fund operations into the second half of 2024.

·Research and development expenses: Research and development expenses were $20.4 million in 2021 compared to $14.4 million in the prior year. The increase in R&D expenses was primarily due to increased spending on the development of VTP-200, VTP-300, and VTP-850.

·General and administrative expenses: General and administrative expenses were $25.1 million in 2021 compared to $10.5 million in the prior year. This includes the share-based payment charge of $14.2 million and $6.0 million unrealized foreign exchange gain on revaluation of Company’s cash balances recorded in 2021. Net of this gain, the increase in general and administrative expenses between the periods was mainly attributable to higher personnel costs, reflecting an increase in the Company’s headcount over the period and higher insurance costs associated with operating as a public company.

·Net loss: The Company generated a net loss attributable to its shareholders of $50.9 million, or $1.96 per share on both basic and fully diluted bases in 2021, compared to a net loss of $17.7 million, or $2.24 per share on both basic and fully diluted bases, for the prior year.