On August 15, 2022 AstraZeneca reported that Positive high-level results from the DESTINY-Breast02 Phase III trial of Enhertu (trastuzumab deruxtecan) versus physician’s choice of treatment showed the trial met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1) (Press release, AstraZeneca, AUG 15, 2022, View Source [SID1234618345]). The trial also met the key secondary endpoint of improved overall survival (OS).

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The trial evaluated a similar later-line patient population as the single-arm DESTINY-Breast01 Phase II trial, which was the basis for initial approvals in advanced HER2-positive metastatic breast cancer. The safety profile of Enhertu in DESTINY-Breast02 was consistent with previous Phase III clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) rates and severity were consistent with those observed in other metastatic breast cancer trials of Enhertu, with a low rate of Grade 5 ILD events observed as determined by an independent adjudication committee.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, "The DESTINY-Breast02 trial results in this patient population with advanced disease confirm the efficacy and safety profile seen in DESTINY-Breast01 and are consistent with the results seen across our broader clinical programme in HER2-positive metastatic breast cancer. These data further strengthen our confidence in Enhertu and reinforce its potential to transform patient outcomes across multiple treatment settings."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The top-line results from DESTINY-Breast02 confirm the robust progression-free survival seen in previous trials of Enhertu and enrich our clinical understanding of the benefit this therapy may offer patients with HER2-positive metastatic breast cancer. As this is the confirmatory trial for our current breast cancer indication in Europe and several other countries, we look forward to sharing these findings with regulatory authorities to add to the body of data for Enhertu for the treatment of HER2-positive metastatic breast cancer."

The data will be presented at a forthcoming medical meeting.

Notes

HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.1 Approximately one in five patients with breast cancer are considered HER2-positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4

DESTINY-Breast02
DESTINY-Breast02 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician’s choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1. Patients were randomised 2:1 to receive either Enhertu or physician’s choice of treatment.

The primary endpoint of DESTINY-Breast02 is PFS based on blinded independent central review (BICR). The key secondary endpoint is OS. Other secondary endpoints include objective response rate based on BICR and investigator assessment, duration of response based on BICR, PFS based on investigator assessment and safety.

DESTINY-Breast02 enrolled approximately 600 patients at multiple sites in Asia, Oceania, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a Food and Drug Administration (FDA)-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu in breast and gastric cancer are currently under review in several countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging and redefining the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the initial approvals of Enhertu, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential use in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

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On August 15, 2022 The Life Raft Group reported it was recently part of team of authors on a collaborative position paper entitled, ‘Undetected KIT and PDGFRA mutations: an under-recognised cause of gastrointestinal stromal tumours (GISTs) incorrectly classified as wild-type’, published in Pathology: The Journal of the Royal College of Pathologists of Australia (Press release, The Life Raft Group, AUG 15, 2022, View Source [SID1234618344]).

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Recent advances in GIST research have provided further insight on the different biomarkers that drive GIST and the technology to identify these biomarkers has also evolved over the years. However, there have been reports of undetected KIT or PDGFRA mutations in GIST resulting in incorrectly classifying some patients as wild-type.

These findings were highlighted in previous publications by Dr. Maria Pantaleo and team. After reviewing these publications, Senior Director of Research & Data Management, Denisse Montoya along with Data Analyst Jerry Call identified two cases from the LRG GIST Patient Registry where two patients were wrongly classified as "wildtype" and an erroneous treatment plan was prescribed. After a more extensive NGS test was performed on these patients, a KIT mutation was discovered, and the right treatment was prescribed to patients which later showed successful shrinkage and results. Executive Director Sara Rothschild leveraged her knowledge of the subject matter and networked with Dr. Maria Pantaleo and team to discuss this issue and informed her about the two identified cases.

Dr. Maria Pantaleo, Dr. Annalisa Astolfi, Dr. Anthony Gill, Dr. Brian Rubin along with the Life Raft team worked together in drafting this important position paper to increase awareness on this critical issue. These findings highlight the need for advanced biomarker testing for patients with KIT/PDGFRA wildtype GIST, to further identify and unveil the active biomarkers driving the GIST and hence ensuring that patients receive the appropriate treatment plan. Another key recommendation is that patients that receive a KIT/PDGFRA wildtype GIST diagnosis should be referred to centers with a wide range of experience and have access to the latest NGS-based tools in molecular diagnostic in GIST.

On August 15, 2022, Radius reported connection with the Merger, Parent, Purchaser, as the initial borrower immediately prior to the Merger, and the Company, as borrower after giving effect to the Merger, entered into a credit agreement (the "Credit Agreement") with OrbiMed Royalty & Credit Opportunities III, LP and OrbiMed Royalty & Credit Opportunities IV, LP, as lenders, and Wilmington Trust, National Association, as administrative agent, providing for a $350.0 million senior secured term facility (the "Term Loan") (Filing, 8-K, Radius, AUG 15, 2022, View Source [SID1234618343]). The proceeds of the Term Loan were used on the closing date under the Credit Agreement to finance the transactions contemplated by the Merger Agreement, to refinance certain existing indebtedness of the Company and to pay related fees and expenses.

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The Term Loan will mature on August 15, 2028. The Term Loan will start amortizing on the 37-month anniversary of the closing date, with equal monthly installments of principal due through the maturity date.

Borrowings under the Term Loan bear interest at a rate per annum equal to the greater of (a) 30-day average SOFR and (b) one-half percent (0.50%) per annum, in either case, plus the applicable margin of eight percent (8.00%) per annum ("Interest"). For the first twelve (12) months after the closing date, the Company will have the option to accrue up to one-half percent (0.50%) of the Interest as a payable in kind.

The Credit Agreement contains representations and warranties, covenants and events of default customary for agreements of this type.

Supplemental Indenture for Convertible Notes

In connection with the consummation of the Merger, the Company and Wilmington Trust, National Association, as trustee (the "Trustee"), entered into a Second Supplemental Indenture, dated as of August 15, 2022, which amends and supplements the Base Indenture, dated as of August 14, 2017, by and between the Company and the Trustee (the "Base Indenture"), as supplemented by the First Supplemental Indenture, dated as of August 14, 2017, by and between the Company and the Trustee (the "First Supplemental Indenture"), governing the Company’s 3.00% Convertible Senior Notes due 2024 (the "Notes") in the aggregate outstanding principal amount of approximately $193,000,000. The Second Supplemental Indenture was entered into to provide for a change in the conversion right of the Notes resulting from the Merger.

The Second Supplemental Indenture provides that, from and after the effective time of the Merger (the "Effective Time"), the right to convert each $1,000 principal amount of the Notes based on a number of Shares equal to the Conversion Rate (as defined in the First Supplemental Indenture) in effect immediately prior to the Merger will be changed into a right to convert such principal amount of Notes based on a number of units of reference property equal to the Conversion Rate consisting of (i) prior to the Milestone Payment Date (as defined in the CVR Agreement), $10.00 in cash and one (1) CVR, and (ii) after the occurrence of the Milestone Payment Date, $10.00 in cash plus the Milestone Payment Amount (as defined in the CVR Agreement) in cash.

The Second Supplemental Indenture also provides that the Company irrevocably elects to eliminate Cash Settlement and Combination Settlement (each as defined in the First Supplemental Indenture) and that its obligations to convert the Notes will be satisfied solely by Physical Settlement (as defined in the First Supplemental Indenture).

The foregoing description of the Base Indenture, the First Supplemental Indenture and the Second Supplemental Indenture does not purport to be complete and is subject to, and qualified in its entirety, by the full text of the Base Indenture and the First Supplemental Indenture, which were included as Exhibits 4.1 and 4.2, respectively, to the Company’s Current Report on Form 8-K, filed with the SEC on August 14, 2017, and is incorporated into this Item 1.01 of this Current Report on Form 8-K by reference, and the full text of the Second Supplemental Indenture, which is included as Exhibit 10.1 hereto, is incorporated herein by reference.

On August 15, 2022 Boston Scientific Corporation (NYSE: BSX) reported the acquisition of Obsidio, Inc., a privately-held company that has developed the Gel Embolic Material (GEM) technology used for embolization of blood vessels in the peripheral vasculature (Press release, Boston Scientific, AUG 15, 2022, View Source,-Inc [SID1234618342]).

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Embolization is a minimally invasive procedure intended to obstruct or reduce blood flow to an abnormality or tumor to stop hemorrhaging, reduce the size of malignant and benign tumors, and stabilize venous and arterial malformations.

Recently cleared by the U.S. Food and Drug Administration (FDA), the GEM technology is a semi-solid, proprietary material packaged in a ready-to-use form, thus reducing the preparation time required for many embolization procedures. Physicians deliver the GEM agent through a catheter, and its gel-like composition enables controlled placement within patient anatomy. Unlike solid and liquid embolics that can take time to form an obstruction to blood flow, once placed, the GEM technology conforms to the targeted vasculature, immediately creating a barrier.

"The GEM technology combines benefits of currently available embolics, such as precise control of a solid and malleability of a liquid, to create a unique technology that offers procedural efficiency and a more personalized therapy for patients," said Peter Pattison, president, interventional oncology and embolization, Peripheral Interventions, Boston Scientific. "This acquisition strengthens our interventional oncology and embolization portfolio with a differentiated solution for physicians and their patients suffering from hemorrhages, cancer and other debilitating conditions."

The transaction is expected to be immaterial to Boston Scientific’s GAAP and adjusted earnings per share in 2022. Specific terms of the transaction have not been disclosed.

On August 15, 2022 Sigyn Therapeutics, Inc. (OTCQB: SIGY), a development-stage company focused on the creation of therapeutic solutions that address unmet needs in global health, reported its financial results for the second quarter ended June 30, 2022 and provides an update on recent corporate developments (Press release, Sigyn Therapeutics, AUG 15, 2022, View Source [SID1234618341]).

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"We continue to take meaningful steps toward our goal to advance Sigyn Therapy into human clinical studies," commented Jim Joyce, co-founder and CEO of Sigyn Therapeutics. "Of particular note was our successful completion of in vivo animal studies, which followed a series of in vitro studies that demonstrated the ability of Sigyn Therapy to isolate and extract pathogen sources of life-threatening inflammation in concert with the broad-spectrum depletion of proinflammatory cytokines from human blood plasma. The data from these studies is being incorporated into an Investigational Device Exemption that we are drafting for submission to the U.S. Food and Drug Administration to support potential human studies of Sigyn Therapy in the United States."

Sigyn Therapy is multi-function blood purification technology designed to treat life-threatening infections and inflammatory disorders that are not addressed with approved drugs. In vitro study validations of pathogen sources of life-threatening inflammation include endotoxin (a gram-negative bacterial toxin), peptidoglycan and lipoteichoic acid (gram-positive bacterial toxins), and viral pathogens, including COVID-19. In vitro study validations of inflammatory cytokines include interleukin-1 beta (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-a).
Based on these capabilities, the Company believes that Sigyn Therapy is a candidate to treat pathogen-associated sepsis (leading cause of hospital deaths), community acquired pneumonia (a leading cause of death among infectious diseases), emerging pandemic threats, and hyperinflammation & endotoxemia that commonly occurs in end-stage renal disease patients.

Recent 2022 Developments

Reported the successful completion of in vivo animal studies conducted at the University of Michigan.
Appointed accomplished financial executive, Jeremy Ferrell, CPA, MBA as Chief Financial Officer.
Established a Scientific Advisory Board comprised of recognized clinician researchers and thought leaders from the fields of nephrology, neurology, hepatology, and liver transplantation.
On August 3, 2022, announced that its securities had graduated from trading on the OTC Pink Market to the OTCQB Venture Exchange, and confirmed the Company continues to pursue the listing of its securities on a major exchange.
Summary Second Quarter 2022 Financial Results
For the quarter ended June 30, 2022, the Company had a loss from operations of approximately $533,000, compared to an operating loss of approximately $442,000 for the comparable period of 2021. The Company’s net loss for the 2022 second quarter was approximately $666,000, or approximately $0.02 per share, compared to a net loss of approximately $650,000, or approximately $0.02 per share, for the comparable period in 2021. Second quarter 2022 net cash used in operating activities was approximately $395,000.

For complete financial results, please see Sigyn Therapeutics’ filings at www.sec.gov, and on the Company’s website at www.SigynTherapeutics.com under "Financial Info" in the Investors section.