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Echosens and Novo Nordisk Announce Partnership to Increase Awareness and Advance Early Diagnosis of NASH

On June 22, 2022 Echosens, a high-technology company offering liver diagnostic solutions, and Novo Nordisk A/S, a leading global healthcare company, reported a partnership to advance early diagnosis of non-alcoholic steatohepatitis (NASH) and increase awareness of the disease among patients, healthcare providers and other stakeholders (Press release, Novo Nordisk, JUN 22, 2022, View Source [SID1234616187]).

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NASH is a chronic metabolic liver disease that affects more than 115 million people worldwide1. The condition is caused by build-up of fat and inflammation in the liver. This causes progressive damage to the liver and can lead to end-stage liver disease and death.

NASH is a ‘silent’ disease due to lack of symptoms in the early stages and, as a result, it is estimated that nine out of 10 people living with NASH go undiagnosed2. To significantly increase early diagnosis, broadly accepted non-invasive tests for diagnosing people living with NASH are needed, as confirmatory diagnosis currently relies on an invasive procedure known as a liver biopsy.

Echosens and Novo Nordisk will collaborate to support additional clinical validation, generation of real-world evidence and adoption of non-invasive diagnostic tests for NASH and work together to increase awareness of the disease and the importance of early diagnosis and management. The companies have a shared ambition of doubling diagnostic rates for people living with advanced to severe NASH by 2025.

"NASH is the more severe form of non-alcoholic fatty liver disease (NAFLD). It has few non-specific or no symptoms in its early stage, leading to inappropriate referrals to secondary care and patients often remaining undiagnosed until irreversible complications occur," said Dominique Legros, CEO at Echosens. "There is a pressing need for a broader adoption of our non-invasive liver tests to improve the diagnosis of people living with NASH, and we are proud to partner with Novo Nordisk to combine our strengths and shared mission to empower medical professionals with improved ways to assess, diagnose and manage the condition."

NASH is more common in people living with obesity (82% of people with NASH are living with obesity) and conditions related to obesity, such as type 2 diabetes (44% of people with NASH are living with type 2 diabetes)3. The low diagnosis rate for NASH is partly caused by a lack of awareness of the condition and associated risk factors among at-risk patients, healthcare providers, payers and policymakers.

"At Novo Nordisk we are committed to driving change in NASH, to develop new treatment options and advance care for this serious, chronic disease. An important step towards realizing that ambition is to ensure that we can identify the people in need of care," said Camilla Sylvest, executive vice president for Commercial Strategy & Corporate Affairs at Novo Nordisk. "But we cannot solve this challenge alone and through our partnership with Echosens, we hope to leverage our complementary skills to meet the needs of patients, healthcare providers and other stakeholders striving to address this ‘silent’ epidemic."

About NASH

Non-alcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD). It is a progressive metabolic liver disease characterised by fat accumulation and inflammation in the liver, which can lead to scarring, or fibrosis, and eventually end-stage liver disease and death. The risk of progression to advanced liver disease, including liver cancer, is higher in people with NASH than in the general population, and NASH is predicted to be the leading cause of liver transplantation by 2030. Moreover, NASH increases the risk of developing cardiovascular disease. Currently, no treatment is globally approved for the treatment of NASH, and people with NASH are left with very few management options.

Trastuzumab Deruxtecan Type II Variation Application Validated by EMA for Patients with HER2 Low Metastatic Breast Cancer with HR Positive and HR Negative Disease

On June 22, 2022 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the Type II Variation application for trastuzumab deruxtecan as monotherapy for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy (Press release, Daiichi Sankyo, JUN 22, 2022, View Source [SID1234616186]). Patients with hormone receptor (HR) positive breast cancer must additionally have received or be ineligible for endocrine therapy.

Trastuzumab deruxtecan is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). This application is based on data from the DESTINY-Breast04 phase 3 trial recently presented at the plenary session of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO22) Annual Meeting and simultaneously published in The New England Journal of Medicine.

"Trastuzumab deruxtecan is the first HER2 directed therapy to demonstrate a survival benefit in patients with HER2 low metastatic breast cancer. We now have the potential to redefine how we classify and treat approximately half of all metastatic breast cancers," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Clinical Development, Oncology R&D, Daiichi Sankyo. "In addition to the ongoing review of two other applications for the treatment of patients with HER2 positive metastatic breast cancer or gastric cancer in Europe, we are pleased to have received this third validation for HER2 low metastatic breast cancer with the goal of bringing trastuzumab deruxtecan to as many eligible patients with HER2 targetable cancers as possible."

In DESTINY-Breast04, trastuzumab deruxtecan demonstrated superior and clinically meaningful efficacy in progression-free survival (PFS) and overall survival (OS) in previously treated patients with HER2 low unresectable and/or metastatic breast cancer with HR positive or HR negative disease versus standard of care physician’s choice of chemotherapy. The safety profile of trastuzumab deruxtecan was consistent with previous clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) or pneumonitis rates were consistent with that observed in late-line HER2 positive breast cancer trials of trastuzumab deruxtecan with a lower rate of grade 5 ILD observed, as determined by an independent adjudication committee.

About DESTINY-Breast04

DESTINY-Breast04 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan (5.4 mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR positive or HR negative, unresectable and/or metastatic breast cancer with low HER2 expression previously treated with one or two prior lines of chemotherapy. Patients were randomized 2:1 to receive either trastuzumab deruxtecan or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in patients with HR positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomized patients (HR positive and HR negative disease), OS in patients with HR positive disease and OS in all randomized patients (HR positive and HR negative disease). Other secondary endpoints include PFS based on investigator assessment, objective response rate based on BICR and on investigator assessment, duration of response based on BICR and safety. DESTINY-Breast04 enrolled 557 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About Breast Cancer and HER2 Expression

Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million cases of breast cancer were diagnosed in 2020 resulting in nearly 685,000 deaths globally.1 In Europe, approximately 531,000 cases of breast cancer are diagnosed annually.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumors.3

HER2 expression is currently defined as either positive or negative, and is determined by an IHC test which estimates the amount of HER2 protein on a cancer cell, and/or an ISH test, which counts the copies of the HER2 gene in cancer cells.3,4 HER2 positive cancers are defined as IHC 3+, IHC 2+/ISH+.3 HER2 negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.3 Approximately half of all patients with breast cancer have tumors with a HER2 IHC score of 1+, or a HER2 IHC score of 2+ in combination with a negative ISH test, an expression level not currently eligible for HER2 targeted therapy.5,6,7,8 Low HER2 expression occurs in both HR positive and HR negative disease.9

HER2 testing is routinely used to determine appropriate treatment options for patients with metastatic breast cancer. Targeting the lower range of expression in the HER2 spectrum may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.10 Currently, patients with low HER2 expression with HR positive tumors have limited treatment options following progression on endocrine (hormone) therapy.11 Few targeted options are available for those who are HR negative.12

About Trastuzumab Deruxtecan

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) is approved in Canada, Israel and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a 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 results from the DESTINY-Breast03 trial. Trastuzumab deruxtecan also is approved in approximately 40 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.

Trastuzumab deruxtecan (6.4 mg/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.

About the Trastuzumab Deruxtecan Clinical Development Program

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

Regulatory applications for trastuzumab deruxtecan are currently under review in China, Europe, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Trastuzumab deruxtecan also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Trastuzumab deruxtecan was granted Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of the DESTINY-Breast04 trial. Patients with HR positive breast cancer should additionally have received or be ineligible for endocrine therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.

Biogen and Happify Health Collaborate to Support Multiple Sclerosis Patients on Digital Platform

On June 22, 2022 Biogen (NASDAQ:BIIB) and Happify Health (www.HappifyHealth.com), the Intelligent Healing Company, reported a collaboration to provide a digital solution for patient education and engagement, powered by artificial intelligence (AI), to support people living with multiple sclerosis (MS) (Press release, Biogen, JUN 22, 2022, View Source [SID1234616185]). Through this collaboration, Biogen and Happify Health will help people with MS manage their care journey, improve their wellbeing, learn about treatment options, consult with experts, and connect with other people in the MS community for support.

More than 2.3 million people live with MS globally, including over 1 million people in the United States, according to the National MS Society. Women are two to three times more likely to develop MS than men1.

"This collaboration is one of many ways we are focused on supporting patients by meeting them where they are. The combination of Biogen’s expertise in neuroscience and our commitment to digital health, along with Happify Health’s AI and digital therapeutic capabilities will help drive a connected and comprehensive experience that allows patients to feel supported throughout their journey," said Jason Hawbecker, Head of Strategic Partnerships & Collaborations at Biogen. "We are excited about the potential of this partnership to provide overall support for the MS community."

The Happify Health solution, which brings together a digital tool configured for MS and a care community (Kopa), offers holistic health and wellness support, with access to neurology providers (doctors, nurse practitioners, physicians assistants and nurses) as well as mental health specialists, dietitians, and rehabilitation professionals. The online community that recently launched provides a place for those living with MS to ask experts questions and discuss the physical and mental challenges they are facing with patients in similar stages. Happify Health uses its proprietary AI technology to personalize content to patients’ life stages, symptoms and interests.

"It can be challenging for people living with MS to stay up-to-date with the latest treatments, interpret new symptoms, or investigate changes in their health that may or may not be related to MS," said Ofer Leidner, President of Happify Health. "We are providing the MS community with a solution configured to accommodate their specific needs, as well as opportunities to engage with experts, receive curated content, and discuss disease management with other community members. We are very excited to partner with Biogen on this opportunity given their leadership in the MS space."

Biogen, a global leader in developing treatments for people living with serious neurological and neurodegenerative diseases, will provide support for the MS platform, including educational content and resources for the patient care journey. The company is a global leader in treating MS with a portfolio of medicines to treat relapsing forms of MS, characterized by periods where symptoms subside, with full or partial recovery, and there is no disease progression between attacks.

In addition to psoriasis and maternal health, MS is the third therapeutic area to be addressed through Happify Health’s unique SequenceTM approach. Sequences are configured to support specific medical conditions and weave together components like evidence-based digital therapeutics, online communities, and coaching in one unified platform, with recommendations tailored for each individual.

Propanc Biopharma’s CSO Hails Dostarlimab’s Impressive Results Whilst Acknowledging More Work to Be Done in the Fight Against Cancer

On June 22, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the results from a small trial of just 18 rectal cancer patients in complete remission using an immunotherapy called dostarlimab are "impressive," whilst acknowledging there’s more work to be done (Press release, Propanc, JUN 22, 2022, View Source [SID1234616184]). Chief Scientific Officer and Co-Founder, Dr Julian Kenyon MD, MB, ChB, believes that the field’s biggest challenge remains that immunotherapies work inconsistently across cancers. Oncologists estimate a response rate of 20% across cancer types, according to the Wall Street Journal ("WSJ"). The drugs can wipe out cancers from some people, but fail to work for others. It is also uncertain whether the cancer may eventually return once a patient is in remission, even after a prolonged period of time.

Immunotherapies like dostarlimab, known as a checkpoint inhibitor, seek to inhibit key regulators of the immune system that when stimulated, reduces the body’s immune response to fight cancer. Given that immunotherapies target specific gene sequences, it often means they can encounter resistance, due to mutations that occur and genetic variation even within the primary tumor of a patient. As a result, Dr Cercek, from Memorial Sloan Kettering, who conducted the study for dostarlimab, estimates only 10% of rectal cancer patients and about 4% of all cancers will respond to treatment, according to the WSJ.

"For many cancers, multiple factors can drive growth, making it hard to effectively match one biomarker, or a particular gene sequence, to a single drug. On the other hand, a therapeutic approach like our lead product candidate, PRP, which alters the characteristics of the cancer cell, by enforcing it to express proteins it normally wouldn’t, means the treatment is less likely to encounter resistance through mutations, which is what we have observed in the lab as well as in clinical practice," said Dr Julian Kenyon.

In addition to specifically selecting the 18 rectal cancer patients according to their genetic biomarker, the trial included patients that were pre-metastatic, where tumors were locally advanced in one area, but not spread to other organs. This means patients identified with metastatic cancer were excluded from the trial. Therefore, the treatment and prevention of metastatic cancer, the main cause of patient death for sufferers, still remains the unsolved, final frontier. Cancer stem cells, which are the cells responsible for spreading to other parts of the body, remains a key focus for Dr Kenyon.

Dr Kenyon said, "PRP is a proenzyme treatment that targets and eradicates cancer stem cells by altering multiple pathways of a cancerous cell rather than a single genetic sequence. We’ve observed that once they are treated with PRP, the effects are irreversible and are more easily recognizable by the immune system, therefore potentially improving the response rates of standard approaches like immunotherapy, to overcome advanced cancers. We look forward to testing the utility of PRP with these approaches as we further advance into the clinic."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

Mustang Bio Announces Orphan Drug Designation Granted to MB-106, a CD20-targeted, Autologous CAR T Cell Therapy for the Treatment of Waldenstrom Macroglobulinemia

On June 22, 2022 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to MB-106, Mustang’s CD20-targeted, autologous CAR T cell therapy for the treatment of Waldenstrom macroglobulinemia ("WM" or "Waldenstrom"), a rare type of B-cell non-Hodgkin lymphoma ("B-NHL") (Press release, Mustang Bio, JUN 22, 2022, View Source [SID1234616183]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch") to treat patients with relapsed or refractory B-NHLs and chronic lymphocytic leukemia ("CLL").

The FDA grants Orphan Drug Designation to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers. If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are very pleased to receive Orphan Drug Designation from the FDA, as it is an important regulatory milestone for Mustang’s MB-106 program for the treatment of Waldenstrom macroglobulinemia, a rare B-NHL with a significant unmet medical need. We look forward to dosing the first patient in our multicenter Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and CLL under Mustang’s IND shortly. In the Phase 1 portion of this trial, MB-106 dose escalation will proceed in three separate arms, and Waldenstrom patients will be included in the indolent lymphoma arm in parallel with accrual of patients to the aggressive lymphoma and CLL arms."

MB-106 data presented earlier this month at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress continue to demonstrate high efficacy and a very favorable safety profile across all five dose levels. The overall response ("ORR") was 96% across all dose levels and all indications (n=26). In particular, the 100% complete response rates by PET scan of patients with WM (n=2) as well as of patients with B-NHL previously treated with CD19-directed CAR T cell therapy (n=2) underscore the potential for MB-106 to treat these patient populations with high unmet needs. Durable responses were observed in a wide range of hematologic malignancies including follicular lymphoma, CLL, diffuse large B-cell lymphoma and WM. The possible outpatient administration of this therapy makes it potentially even more compelling. Currently no CAR T therapy is specifically approved for WM.

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

About Waldenstrom Macroglobulinemia
Waldenstrom macroglobulinemia ("WM"), also known as lymphoplasmacytic lymphoma, is a rare type of non-Hodgkin lymphoma ("NHL"), a malignant disorder of the bone marrow and lymphatic tissues. The proliferation of cancer cells can crowd out normal cells in these tissues, leading to low levels of red blood cells, white blood cells, and platelets which, in turn, causes fatigue, shortness of breath, infections, bruising, and bleeding. In addition, the cancer cells make large amounts of the large antibody protein immunoglobulin M, or IgM, which cause the blood to become thick. This hyperviscosity of the blood affects its flow through the smaller blood vessels, leading to some of the other manifestations of the disease, such as visual and neurological symptoms. WM is a rare disorder with an incidence of approximately 3 per million people per year, and 1,400 new cases are diagnosed in the U.S. each year. The median age at diagnosis is 70 years.

About MB-106 (CD20-targeted autologous CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody. MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch will be used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial that is now open to enrollment under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on these trials can be found at View Source using the identifier NCT05360238 for the Mustang multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch.