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MedNess: bite-size biopharma and medtech news

13th January, 2021
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HIGHLIGHTS
Onco-I-Analyse
Merus’ Zenocutuzumab receives Fast Track Designation for NRG1 fusion positive tumors
On 7th January, FDA granted Fast Track designation to HER3xHER2 bispecific antibody Zenocutuzumab (Zeno) for patients with metastatic solid tumors harboring NRG1 gene fusions (NRG1+ cancers) following progression on standard of care therapy.
Background: NRG1 fusions are rare but actionable genomic alterations, first reported in 2014. The most reported NRG1 fusion is CD74-NRG1, mostly occurring in patients with invasive mucinous adenocarcinomas (IMAs) of the lung. Although, NRG1 fusions account for <1% incidence across tumor types, they are enriched in IMA (10%–30% incidence). Other NRG1-positive tumors include gallbladder, renal cell, bladder, ovarian, pancreatic, breast, neuroendocrine tumors, sarcoma, and colorectal.
NRG1 fusions drive tumor development through ERBB receptor-mediated MAPK and PI3K signaling pathways, thus presenting a rational candidate for targeted treatment. Currently there are no approved therapies to target NRG1 fusions and standard therapies include chemotherapy and/or checkpoint inhibitors. However, these have not shown to confer much clinical benefit. Zenocutuzumab’s unique ‘DOCK & BLOCK®’ mechanism inhibits NRG1+-driven tumor growth.
Details: FDA’s fast track designation is to facilitate the clinical development of zenocutuzumab in NRG1+ cancer patients. In 2019, data from a Zeno PoC study demonstrated tumor shrinkage & symptom improvements in NSCLC and pancreatic cancer patients. Also, safety analysis in >100 patients show extremely well tolerability with mostly grade 1-2 AEs.
The ongoing Ph 1/2 eNRGy study is enrolling patients into 3 NRG1+ cohorts - NSCLC, pancreatic cancer and solid tumors. Merus expects program update in 2Q 2021.
Implications: Additional assets being investigated in various Ph 2 trials in NRG1-fusion+ve tumors – Afatinib (in metastatic or locally advanced (LA) NRG1-rearranged malignancies; German Cancer Research Center); Seribantumab (in recurrent, LA or metastatic NRG1-fusion solid tumors; Elevation Oncology) and Tarloxotinib (in NRG1-fusion solid tumors; Rain Therapeutics).
COVID Special
Regeneron announces encouraging initial results from the ongoing clinical trial involving the use of antibody cocktail in hospitalized patients on low-flow oxygen 
Towards the end of December 2020, Regeneron announced encouraging data from an ongoing Phase 1/2/3 clinical trial. This trial is currently looking into the efficacy of an antibody cocktail in hospitalized COVID-19 patients who are on low-flow oxygen. The antibodies in question are casirivimab and imdevimab. The primary clinical aim of the initial analysis was to understand if the antibody cocktail provided sufficient efficacy in the patients without baseline antibodies, to continue the analysis. In other words, they performed the futility analysis. The initial analysis showed that the seronegative patients who were treated with the antibody cocktail had a lower risk of death or receiving mechanical ventilation. Based on the post-hoc analysis, the risk of death and the need of mechanical ventilation was reduced by almost half.
"We appreciate the continued support of patients and investigators around the world who are working to advance Regeneron's antibody cocktail trials under very challenging circumstances," said David Weinreich, M.D., Senior Vice President and Head of Global Clinical Development at Regeneron. "Hospitalizations due to COVID-19 are increasing around the globe and have devastating consequences for these patients, their families and those who care for them, highlighting the need for effective therapeutics. We plan to share these most recent data with regulatory authorities."
Pfizer and BioNTech announce positive results from an in vitro study to show the effectiveness of their COVID-19 vaccine against a mutation associated with rapid transmission 
Pfizer and BioNtech recently released results from an in vitro study that looked at the effectiveness of the Pfizer and BioNtech vaccine against neutralizing a SARS-CoV-2 mutation that has been found in two highly transmissible strains. The study was conducted by Pfizer and the University of Texas Medical Branch (UTMB).
BioNTech believes that their mRNA platform is adept to handle any adjustments to the vaccine if further data shows that the current vaccine needs to be modified to protect against the mutated forms of SARS-Cov-2.
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
Regulatory News
Registration-Enabling Study of eganelisib + Opdivo® planned in platinum-refractory, I/O naïve patients with advanced, metastatic urothelial cancer (mUC)
“The MARIO-275 study provided Infinity with important insights to shape the future of eganelisib in urothelial cancer,” said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. “The data from the 49 patients enrolled in the study are very encouraging. The combination was well tolerated at the 30 mg dose of eganelisib and provided patient benefit relative to the placebo controlled arm on important response rate and progression free survival measures, particularly in urothelial cancer patients with low levels of PD-L1 expression who respond poorly to checkpoint inhibitors alone. We are leveraging the clinical and translational learnings from MARIO-275 in planning a new, registration-enabling study of eganelisib in patients with advanced urothelial cancer. We look forward to presenting our data from MARIO-275, which support our clinical strategy, at a major medical meeting in Q1 2021, with details for our new, planned trial to follow in the coming months after discussions with regulatory authorities.”
Tiragolumab granted FDA Breakthrough Therapy Designation in combination with Tecentriq for PD-L1-high NSCLC patients
“We have been researching TIGIT as a novel cancer immunotherapy target for almost ten years and we are pleased that the FDA has acknowledged the potential of tiragolumab to substantially improve outcomes for people with certain types of lung cancer,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We look forward to advancing our tiragolumab development programme, which includes chemotherapy-free combinations and trials in early stages of disease across multiple cancer types with high unmet need.”
Clinical Hold Letter issued from U.S. FDA Related to CMC Assay Development for NL-201
“We will work diligently to address the FDA’s questions as quickly as possible,” said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. “We believe that we will be able to develop the requested assay and respond within the next several months. While we do not have a definitive timeline as to when we will be able to obtain clearance to proceed, we look forward to working with the FDA to satisfy their requests.”
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Trial Results
Updated OS data from Ph 3 IMbrave150 study of Tecentriq® (atezolizumab) + Avastin® (bevacizumab), vs sorafenib, in 1L unresectable HCC patients to be presented
“These results show that Tecentriq in combination with Avastin provides the longest survival that we’ve ever seen in a front-line Phase III study in unresectable HCC,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The combination, which has now been approved in more than 60 countries around the world, represents a significant treatment advancement for patients with this challenging malignancy.”
Trial/Program Status
Following successful FDA meeting, UPLIFT registrational trial of XMT-1536 in platinum-resistant ovarian cancer planned in Q1 2021
“2021 promises to be another transformative year for Mersana’s pipeline. Our focus will be to initiate the UPLIFT single-arm registration strategy for XMT-1536 in platinum-resistant ovarian cancer and to initiate the UPGRADE combination umbrella study with the goal of informing the path into earlier lines of ovarian cancer therapy. The updated data being presented today show encouraging response rates in late-stage ovarian cancer patients and tolerability further supporting the potential of this therapy to be foundational for the treatment of ovarian cancer,” said Anna Protopapas, President and CEO of Mersana Therapeutics. “Additionally, both the non-small cell lung cancer cohort of the Phase I expansion study of XMT-1536 and the XMT-1592 Phase 1 dose escalation study continue to actively enroll patients with interim data for both studies expected in the second half of this year. We will also work to advance XMT-1660, our first-in-class ADC targeting B7-H4, and XMT-2056, our first Immunosynthen STING-agonist ADC development candidate, through IND-enabling studies.”
Ph 3 Trial of Tisotumab Vedotin Announced in Recurrent or Metastatic Cervical Cancer
“Currently, there is no established standard of care for women with recurrent or metastatic cervical cancer, who have disease progression after first or second line of therapy. There is a need for a novel, safe and effective treatment option that can improve the clinical outcome for these patients,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “We look forward to the innovaTV 301 trial which is designed to support potential regulatory applications for marketing approval globally and serve as a confirmatory trial for a potential accelerated approval in the US for patients with metastatic or recurrent cervical cancer.”
First patient dosed with DLL3-targeting TriTAC HPN328 in Ph 1/2 trial in patients with SCLC and other tumors associated with DLL3 expression
“We are pleased with the rapid progress of our clinical programs, based on our proprietary TriTAC platform, with patient dosing now underway for our fourth product candidate, HPN328, that targets DLL3,” said Natalie Sacks, M.D., Chief Medical Officer of Harpoon Therapeutics. “Treatment options for small cell lung cancer are limited, as are options for other DLL3-associated tumors such as neuroendocrine prostate cancer. Data from preclinical studies suggest that HPN328 has substantial anti-tumor activity, which provides the rationale for investigating its potential benefit in these patients.”
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Collated by : Richa Tewari, PhD
Medness Plus
FDA issues marketing authorization to a new implant to serve as an alternative to anterior cruciate ligament reconstruction 
FDA grants marketing authorization to an anterior cruciate ligament (ACL) implant which aims to serve as an alternative to ACL reconstruction. It is currently the only available alternative to reconstruction with autograft, allograft or suture-only repair for ACP tears or ruptures. The Bridge-Enhanced ACL Repair (BEAR) Implant does not use the traditional harvested tendons for ACL repair. It is indicated for use in skeletally mature patients over the age of 14 years with a complete rupture of the ACL. They must have an ACL stump attached to the tibia to aid the repair. The marketing authorization was granted to Miach Orthopedics, Inc. The application was reviewed through the De Novo premarket review pathway. This pathway is used for low-to-moderate-risk devices of a new type. The FDA will issue special controls for similar devices and a combination of this and general controls will give a reasonable assurance of the safety and efficacy of the device.
“Torn ACLs are among the most common knee injuries in the U.S., but for years, treatment has been limited to ACL reconstruction, which can be quite invasive and typically requires using tendon or a combination of tendon and bone from other parts of the body, or obtained from a tissue bank, to complete the reconstruction,” said Capt. Raquel Peat, Ph.D., MPH, USPHS, director of the Center for Devices and Radiological Health’s Office of Orthopedic Devices, “Today’s marketing authorization provides new options for the hundreds of thousands of people affected by ACL rupture in the U.S. each year.” 
FDA grants FARXIGA Priority Review status for the treatment of adults with chronic kidney disease 
FDA grants FARXIFA Priority Review for the treatment of chronic kidney disease (CKD) in adults with and without type 2 diabetes. The Priority Review status was granted to AstraZeneca. Earlier in October 2020, FARXIGA had received a Breakthrough Therapy Designation in the US for patients with CKD with and without type 2 diabetes (T2D). In May 2020, it was approved in the US to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease. Priority review designation is granted to therapies and treatments that have demonstrated efficacy and safety improvements along with preventing serious conditions.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “This decision brings us a step closer to delivering this new treatment option for the millions of patients living with chronic kidney disease in the US. FARXIGA has the potential to be a truly transformational medicine across a breadth of diseases, including type 2 diabetes, heart failure with reduced ejection fraction and, if approved, chronic kidney disease.”
Click here for more MedNess Plus
Collated by : Esha Sehanobish, PhD
Medness @ Health-IT

New NIH fund to augment COVID-testing methodology
To encourage testing and diagnosis solutions for COVID19, NIH has issued a grant of over $107 million, targeted to fund innovative COVID-19 testing and surveillance methods in the US, ranging from artificial intelligence solutions to home-based testing technologies. Keeping future outbreaks in perspective, the program is intended to develop platforms that can be deployed fast for future outbreaks of other infectious diseases. According to NIH Director Francis S. Collins, MD, PhD, “These awards from the RADx-rad program provide superb examples of outside-the-box concepts that will help us overcome this pandemic and give us a cadre of devices and tactics to confront future outbreaks.” Project types may include: 1) Use of AI for detection, diagnosis, prediction, prognosis, and monitoring of diseases, 2) Developing biomarkers and biosignatures for an algorithm using AI to predict the long-term risk of disease severity, 3) Safe and effective biosensing/detection technologies to spot signatures of infection from human skin or mouth, 4) Wastewater technologies and data collection methods for detecting and estimating COVID-19 community infection levels, 5) Detection devices to trace disease spread in real time. Read the full program specification here.
AI comes to aid of tackling incurable diseases
Incurable diseases or undruggable diseases are characterized by specific targets that lie on a protein molecule folding inward, protecting the active site from potential treatments. To bypass the dependency on proteins, a new tool to target RNA has been developed and applied against metastatic breast cancer by a team from Scripps Research. The tool, called Chem-CLIP-Fragment Mapping, speeds up drug discovery efforts by revealing multiple opportunities to bind and modify RNA targets utilizing AI-algorithm and thereby enables a rapid discovery and optimization of RNA-targeting compounds. In this study, the group targeted microRNA-21, a causative agent in aggressive breast cancers. The mapping tool helped identify the relevant RNA after screening 460 fragment-based probe within just a couple hours of time span. Describing the nature of the tool, Dr. Disney stated, “This is a chemical that has a weak magnet-like attraction to other nearby molecules. So when it’s placed near disease-associated proteins, or now RNAs, it can thus bind to them, revealing the shape a medicine would need to take to bind to that disease-associated protein or RNA”. Read the full publication (PNAS) here. 
Targeting Antibiotic resistance through transcriptome database
Researchers from the University of Maryland School of Medicine collaborated with teams from the University of Alabama at Birmingham and Yale University School of Medicine to develop an atlas of transcriptomes or gene expression data, to better understand the growing antibiotic resistance feature in Pneumococcal infection. The database included strains that cause pneumonia, meningitis, and middle ear infections. The team published data to show that there might be a differential pattern of behavior for the pathogen depending on the site of infection, while the host organs may respond differently as well. According to the study co-author Adonis D'Mello, “We were able to build upon analytical pipelines to provide a more comprehensive way of studying diverse systemic pathogens.” Their study shades light on anti-inflammatory treatment called interferon beta as a therapeutic option while exploring antibiotic resistance properties within the Pneumococcal bacteria. Read the full publication here.
Medness Reviews

FDA warns that gold-standard COVID-19 tests may produce false negative results in genetic variants of the virus
The FDA is alerting healthcare professionals that mutations in the novel coronavirus could return false-negative results in gold-standard COVID-19 tests.
The agency said that the accuracy of the tests can suffer if alterations occur in the specific region of the virus RNA that is used by molecular diagnostics for detecting the virus and listed three currently authorized tests - Thermo Fisher’s TaqPath combo kit, Mesa Biotech’s hand-held Accula test and Applied DNA Sciences’ Linea assay that the agency believes may be compromised by genetic variants of the virus.
However, on the flip side, the FDA said that the detection mechanism used by the the detection the TaqPath and Linea tests could help identify new mutated strains of the coronavirus.In wake of the new strains from UK and South Africa, the FDA is now reevaluating all of its authorized molecular tests as well as certain vaccines and treatments to see whether they will work against the genetic variants.
A new and improved polio vaccine joins the eradication efforts towards the disease
The development of vaccines and drugs to address the COVID-19 pandemic has been taking the front seat in the news and the recent vaccine approvals has definitely spurred curiosity within the general public all over the world. Away from the spotlight, the World Health Organization granted its first ever emergency use authorization for a new polio vaccine nOPV2 vaccine (Bio Farma, Indonesia) to address the rising cases of a vaccine-derived polio strain in a number of African and East Mediterranean countries.  
This vaccine approval is yet another effort towards eradicating polio after decades of work and mass vaccination campaigns that have spared millions of children from paralysis.
The nOPV2 oral vaccine was developed to address a small number of vaccine-derived polio outbreaks that in areas of low vaccination. The outbreaks occurred after weakened virus in the oral polio vaccine, over time, moved around a community and regained the ability to cause disease. No other vaccines made with weakened live viruses have caused outbreaks of disease.
More than 80 percent of children need to be vaccinated to keep poliovirus from spreading in a community. The older polio virus vaccine administered a weakened/altered strain of the virus. It not only protects against paralysis — it also can stop wild poliovirus from spreading in a community. Poliovirus is water-borne and transmits when someone ingests water or food contaminated with virus-containing stool. The oral vaccine prevents wild poliovirus from multiplying in the gut and being passed on. Weakened poliovirus in the vaccine has genetic changes that keep it from causing disease. However, over time and mutations, the weakened virus was able to return to a form that caused paralysis and was able to spread within communities that had low numbers of immunized individuals. Today, vaccine-derived outbreaks are primarily found in Afghanistan, Pakistan and countries in Africa.
The solution - Scientists were able to figure out a way to develop new and improved vaccine by simply tweaking the older vaccine. For achieving this, they made genomic alternations in virus that would prevent it from reverting to the virulent or disease-causing form.
The new oral polio vaccine was shown to be safe and to produce an immune response similar to that seen with the original vaccine in infants and children, researchers reported. The hope is that the modifications will slow the evolution of the new vaccine virus such that it can end the existing outbreaks without creating new ones.
Medness Business
Onco-News
Bluebird bio to Separate Oncology Business into Independent Company
“We are excited and energized to begin this new year with so much opportunity ahead. Over the last decade, bluebird bio has pioneered development of gene and cell therapies for severe genetic diseases and oncology - delivering transformative outcomes for patients. Through the tenacity and incredible work of our bluebirds, our first commercial product is now approved in Europe and we are now on the cusp of several potential product approvals with a strong pipeline of earlier oncology research candidates on the horizon. This is a position few biotech companies have been able to attain,” said Nick Leschly, chief bluebird. “After careful strategic review, it is clear to us that the two businesses are best served by independent leadership and teams to drive distinct strategic and operational objectives. Specifically, we believe it is the right time to double down on the respective businesses to fully enable and optimize the continued innovation, development and deployment of transformative gene and cell therapies for the patients we serve.”
Boehringer Ingelheim and Enara Bio enter Strategic Collaboration and Licensing Agreement to discover novel shared antigens for cancer immunotherapies
“We are excited to partner with Enara Bio as part of our mission to bring transformative new treatments to cancer patients,” said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head, Cancer Immunology & Immune Modulation Research, Boehringer Ingelheim. “We are advancing a unique pipeline of cancer cell-directed agents, immuno-oncology therapies and intelligent combination approaches to help combat cancer. Enara Bio’s unique discovery platform offers a novel and highly differentiated approach that will allow us to look beyond the known proteome to identify and characterize Dark Antigens to support the development of T-Cell Receptor (TCR)-directed immunotherapies and therapeutic vaccines. We believe this is a highly innovative and promising approach to the development of the next wave of cancer immunotherapies.”
BioPharma and MedTech
Eligo Bioscience signs a deal with GlaxoSmithKline for the CRISPR based treatment of acne 
On January 11th, 2021 France based Eligo Bioscience entered a research and option deal with GlaxoSmithKline to progress their Eligobiotics platform for the treatment or prevention of acne vulgaris. Under the research agreement, Eligo will earn an upfront payment and R&D funding to advance the EB005 acne treatment program towards the preclinical stage. If GSK utilizes its option, both companies would enter into a license and collaboration agreement to jointly further develop the EB005 in acne. Eligo would receive up to $224 M in license fees and potential milestone payments, as well as royalties on global sales of their products. EB005 is a topical treatment program that is aimed to selectively remove pro-inflammatory bacterial strains from the skin, while the rest of the skin microbiome remains unaffected. Eligobiotics®' RNA-guided CRISPR-Cas strategy can precisely target the specific harmful bacterial strain by utilizing engineered nuclease.
“We are excited to work with GSK on advancing our radically new approach to address acne, combining our unique technology platform with GSK’s scientific excellence and capabilities to bring innovation from the lab bench, through clinical development, and to patients. This early-stage partnership demonstrates the translational potential of Eligo’s technology platform,” - Xavier Duportet, Ph.D., CEO, Eligo Bioscience.
DiCE Molecules secures $80 M Series C funding advancement of its protein-protein interface antagonist pipeline
On January 8th, 2021 California based DiCE Molecules bagged $80 M Series C funding to develop next-generation immunological therapies. The financing round was led by RA Capital Management, Eventide Asset Management, New Leaf Venture Partners, Soleus Capital, Driehaus Capital Management, Osage University Partners and Asymmetry Capital Management and existing investors Northpond Ventures, Sands Capital, Sanofi Ventures, Alexandria Venture Investments, Altitude Life Science Ventures, and Agent Capital. DiCE’s research strategy is based on its DNA-encoded library (DEL) technology that generates small molecules to specifically target protein-protein interactions for difficult to drug diseases. These newly acquired funds will be utilized for the preclinical IL-17 pipeline to treat psoriasis, a skin disease that occurs when the immune system attacks the skin by mistake in the absence of a real infection.
 “This financing will enable us to accelerate our lead IL-17 program through important milestones while advancing our other assets, including a pair of integrin inhibitors, and also expand our pipeline using the same combination of technology and structural insights. We believe the immunology space is underserved by current small molecule approaches and we are excited about the opportunity to advance next-generation therapeutics for this patient population.” - Kevin Judice, Ph.D., CEO, DiCE Molecules.
Click here for more on mergers, acquisition and business news
Collated by : Richa Tewari, PhD and Rinki Saha
Editors' Desk
Richa Tewari, PhD
Oncology News
Esha Sehanobish, PhD
MedNess Plus
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Shilpa Rawal, PhD
Onco I-Analyse
Debarati Banik
HealthIT
Rinki Saha
BioPharma News
Abhi Dey
Consulting Editor
Nisha Peter, PhD
Managing Editor
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The editors take care to share authentic information.  In case of any discrepancies please write to medness.newsletter@gmail.com
The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Medness. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Medness. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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Content Editors: Richa Tewari , Esha Sehanobish , Rinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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