On March 25, 2022 Exicure, Inc. (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported full year financial results for the quarter and year ended December 31, 2021 and provided an update on its business strategy and corporate progress (Press release, Exicure, MAR 25, 2022, View Source [SID1234611018]).

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!

"This past year brought significant challenges to our organization that prompted strategic decisions at year-end to refocus our business strategy on our next generation pipeline and investments in neuroscience in order to be cash efficient," said Matthias Schroff, Ph.D., Chief Executive Officer of Exicure. "Entering 2022, I believe we are off to a good start as we have now fully aligned our resources to support development of our preclinical programs targeting SCN9A for the treatment of pain and advancement of ongoing discovery associated with our Ipsen and AbbVie partner programs. I want to acknowledge our team for their commitment to moving our company forward during this difficult time and thank them for their continued dedication in our mission to pursue treatments for patients with unmet medical needs," concluded Dr. Schroff.

Corporate Progress

Corporate highlights for 2021 include:

•Entered into an exclusive collaboration targeting rare neurodegenerative disorders with Ipsen in July 2021 to research, develop, and commercialize novel Spherical Nucleic Acids (SNAs) as potential investigational treatments for Huntington’s disease (HD) and Angelman syndrome (AS).
•Completed a strategic review in fourth quarter of 2021, which resulted in a restructuring and pipeline focus on preclinical programs targeting SCN9A in pain and partnered programs.
•Completed a $11.5 million registered direct offering in December 2021.

Priorities for 2022 include:

•Advancement of the Company’s SCN9A preclinical discovery program. Exicure anticipates results from initial in vivo animal studies by year-end 2022 with goal of therapeutic candidate selection in the second half of 2023.
•Progressing work with the Company’s partnered programs, with plan of meeting potential pre-clinical milestones in 2023.
•Actively pursuing strategic out-license opportunities for cavrotolimod.
•Ongoing pursuit of near-term partnering opportunities for pain and other neuroscience programs.

2021 Financial Results

Cash Position: Cash, cash equivalents and short-term investments were $48.3 million as of December 31, 2021, as compared to $83.3 million as of December 31, 2020. The Company expects that its cash and cash equivalents will fund its current operations into the fourth quarter of 2022.

Revenue: Revenue was $(0.5) million during the year ended December 31, 2021, reflecting a decrease of $17.1 million from revenue of $16.6 million for the year ended December 31, 2020. The decrease in revenue is mostly due to a decrease in non-cash revenue of $19.3 million associated with the Company’s collaboration with AbbVie partially offset by the recognition of non-cash revenue of $2.3 million associated with the Company’s collaboration with Ipsen. Revenue recognized (reversed) associated with the Company’s collaboration with AbbVie for the year ended December 31, 2021 reflects the cumulative catchup adjustment (reduction) of revenue in connection with the change in estimate that resulted from a change in workplan related to the Company’s collaboration with AbbVie during the third quarter of 2021.

Research and Development (R&D) Expense: Research and development expenses were $49.0 million for the year ended December 31, 2021, as compared to $32.1 million for the year ended December 31, 2020. The increase is due to an increase in clinical trial activities during the year as well as the impact of higher than average headcount during 2021 as compared to the prior year period.

General and Administrative (G&A) Expense: General and administrative expenses were $13.1 million for the year ended December 31, 2021, as compared with $10.0 million for the year ended December 31, 2020. The increase is mostly due to costs related to new hires needed to grow the Company as it evolved, one-time severance costs of $0.6 million associated with the December 2021 restructuring, as well as higher legal costs and other costs associated with being a public company.

Net Loss: The Company had a net loss of $64.1 million for the year ended December 31, 2021, as compared to a net loss of $24.7 million for the year ended December 31, 2020. The increase in net loss was primarily driven by lower non-cash revenue during the period largely impacted by the reversal of non-cash revenue in 2021 associated with Exicure’s collaboration with AbbVie as well as higher R&D and G&A costs as discussed above.
Going Concern: The Company’s expectation to continue to generate operating losses and negative operating cash flows in the future and the need for additional funding to support its planned operations raise substantial doubt regarding its ability to continue as a going concern within one year after the date that its consolidated financial statements for the year ended December 31, 2021 are issued. The Company will require additional financing to address the Company’s working capital and other financing needs.

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 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 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported upcoming presentations on two of its skin cancer gene expression profile (GEP) tests at the 2022 American Academy of Dermatology (AAD) Annual Meeting, being held in Boston, March 25-29, 2022 (Press release, Castle Biosciences, MAR 25, 2022, View Source [SID1234611003]).

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!

"We are pleased to once again have the opportunity to share data supporting the value of our tests in the management of patients with skin cancer," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "Our data presentations at AAD highlight two of our proprietary GEP tests, DecisionDx-Melanoma and DecisionDx-SCC, and their ability to independently risk-stratify patients with melanoma or high-risk squamous cell carcinoma, respectively, to potentially guide better informed and more risk-aligned patient care."

DecisionDx-Melanoma

Title: "The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma"
Poster number: 32344
Presenter: Abel Jarell, M.D., Northeast Dermatology Associates, P.C., Portsmouth, N.H.
Date: Saturday, March 26, 2022
Location: Poster Presentation Center 2 in the Exhibit Hall
Time: 3:30-3:35 p.m. Eastern time

DecisionDx-Melanoma is Castle’s 31-GEP test designed to use a patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors. The test classifies a patient’s tumor as low risk of recurrence/metastasis (Class 1A), increased risk (Class 1B/2A) or high risk (Class 2B).

Consistent with previous studies, the poster reports that DecisionDx-Melanoma significantly stratified patients according to their metastatic risk (RFS, DMFS and MSS p<0.001). Further, the poster data demonstrates DecisionDx-Melanoma’s potential to guide patient care as a significant, independent predictor of metastatic recurrence compared to staging using the American Joint Committee on Cancer Staging Manual Eighth Edition (AJCC8) framework (high-risk Class 2B result: hazard ratio 5.38, p=0.014). Moreover, a high-risk Class 2B DecisionDx-Melanoma test result in Stage I and II patients (classified according to AJCC8 staging) was associated with lower patient survival (DMFS and MSS) than that of Stage III patients, showing that the DecisionDx-Melanoma test result provides additional risk information as a complement to existing melanoma management plans.

Additionally, combining a patient’s DecisionDx-Melanoma test result (specifically, a low-risk Class 1A test result) with sentinel lymph node (SLN) status, a commonly used prognostic indicator, was associated with improved recurrence outcomes compared to relying on a negative or positive SLN status alone (recurrence free was 98.0% for Class 1A/SLN negative vs. 93.8% for SLN negative alone, and 100% for Class 1A/SLN positive vs. 80.4% for SLN positive alone). Similar improvements in recurrence accuracy were observed in the high-risk Class 2B DecisionDx-Melanoma test result (recurrence free was 84.6% for Class 2B/SLN negative vs. 93.8% for SLN negative alone and 73.3% for Class 2B/SLN positive vs 80.4% for SLN positive alone). The results of the study provide further support for the ability of DecisionDx-Melanoma to provide independent risk-stratification to determine the likelihood that a patient’s cancer will spread or recur, as well as complement other risk assessment methods, to guide more precise and personalized patient care.

DecisionDx-SCC

Title: "Clinical usage data demonstrates appropriate utilization of the prognostic 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma with one or more risk factors"
Poster number: 35334
Presenter: Aaron S. Farberg, M.D., Baylor Scott & White Health System, Dallas
Date: Sunday, March 27, 2022
Location: Poster Presentation Center 1 in the Exhibit Hall
Time: 9:30-9:35 a.m. Eastern time

DecisionDx-SCC is Castle’s prognostic 40-GEP test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients diagnosed with cutaneous squamous cell carcinoma (SCC) who have one or more high-risk factors. The test stratifies patients into one of three classes based on their biologic risk of metastasis: Class 1 (low risk), Class 2A (moderate risk) or Class 2B (high risk).

Clinical validity and utility of the DecisionDx-SCC test has been reported. Results of those studies indicate that the information provided by the test can improve stratification of high-risk SCC patients and, if incorporated into clinical assessments with any number of traditional clinicopathologic risk factors, could assist physicians in guiding more risk-appropriate surveillance and treatment decisions.

DecisionDx-SCC is validated for use in patients with high-risk SCC, defined as the presence of one or more clinicopathologic risk factors, and clinical data has demonstrated its ability to accurately and independently stratify patients according to their biologic risk of metastasis. Analysis of one year of real-world clinical data (2,503 DecisionDx-SCC test orders received between Aug. 31, 2020-Aug. 31, 2021) showed that the intended use population (high-risk SCC patients) aligns with the cases submitted for testing, indicating that physicians understand the appropriate use criteria for the test. Of note, within this high-risk population, nearly 70% of patients received a DecisionDx-SCC Class 1 test result, signifying that they have a biologically lower risk for metastasis. Overall, the current study data, combined with the presented previous validation data, indicates that the testing population aligns with a high-risk population.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,000 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through Dec. 31, 2021, DecisionDx-Melanoma has been ordered 90,154 times for use with patients with cutaneous melanoma.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the Castle tests can be found at www.CastleTestInfo.com.

On March 25, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported that Advanced Accelerator Applications, a Novartis company, as a long-term supplier for the medical radioisotope component of the newly U.S. Food and Drug Administration (FDA) approved radiotherapeutic, PluvictoTM (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy (Press release, ITM Isotopen Technologien Munchen, MAR 25, 2022, View Source [SID1234611002]). ITM will now supply its medical radioisotope n.c.a. 177Lu (EndolucinBeta), a core component of the newly approved radiotherapeutic, for the commercial phase based on a supply agreement entered in 2020, supporting the scalability and security-of-supply for patients worldwide.

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!

"As a long-standing supplier of n.c.a. lutetium-177 for Pluvicto, we share in the excitement of this approval," commented Steffen Schuster, Chief Executive Officer of ITM. "At ITM, we strive to provide high-quality radioisotopes not only for our own pipeline, but also for our partners in an effort to bring improved precision oncology treatments to patients on the widest scale possible. We congratulate Advanced Accelerator Applications on its notable achievement and are proud to have contributed clinical supply for the development of this new therapeutic."

ITM has established an industrial scale production of high-quality n.c.a. 177Lu which is intended to be used to damage tumor tissue by emitting a small amount of ionizing beta radiation at short distances thereby minimizing damage to surrounding healthy tissue. ITM’s n.c.a. 177Lu is designed to have an extraordinarily high level of purity which cuts storage and logistic costs otherwise associated with handling contaminated waste and enables its global use in areas adhering to strict radiation protection rules and regulations. ITM holds a U.S. DMF with the FDA for n.c.a. 177Lu and has marketing authorization in the EU (brand name EndolucinBeta).

ITM is a global leader in the production and supply of high-quality medical radioisotopes used as radiopharmaceutical precursors for precise diagnosis and targeted treatment of cancer and has established a wide-reaching international supply network. Furthermore, ITM is developing a proprietary broad pipeline of Targeted Radionuclide Therapies and Diagnostics for various cancer indications which includes its lead candidate, ITM-11 for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), currently being investigated in two phase III clinical trials.

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific entities such as receptors which are expressed on the cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization potentially enables targeted treatment with minimal impact to healthy surrounding tissue.