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MedNess: bite-size biopharma and medtech news

1st September, 2021

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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Novartis’ Kymriah hits roadblock in 2nd line B-cell aNHL
On 24th August, Novartis announced that Kymriah (tisagenlecleucel, CD19- targeting CAR-T) failed to meet the primary endpoint of event-free survival (EFS) in the pivotal Phase 3 BELINDA trial patients with aggressive B-cell non-Hodgkin lymphoma (NHL) after relapse or lack of response to frontline therapy. 
Background: HDCT followed by SCT is considered the gold standard for patients with aggressive B-cell NHL. However, the therapy is very intense with considerable side-effects and is not curative. Thus, there is a significant unmet need for newer, better therapies for patients with R/R LBCL. ​
Details: The
BELINDA trial evaluated Kymriah as second line therapy, against SoC (salvage platimun-based chemotherapy followed by high dose chemotherapy and autologous HSCT in responding patients), in patients with either primary refractory aggressive B-cell NHL or relapse within 12 months of frontline treatment (rituximab and anthracycline containing regimen).
The trial did not show clinically meaningful benefit in the primary endpoint of EFS versus the SoC. Although, the safety profile of Kymriah remained consistent with previous findings.
Novartis and trial investigators will complete a detailed assessment of results and present data at an upcoming meeting.

Kymriah was the first CAR-T to be approved in 2017; its current approved indications included R/R ALL and 3L+ DLBCL where it has demonstrated significant efficacy and favourable safety profile based on RCTs and RWE in over 5,300 patients.
Implications: Kymriah’s failure to show significant improvements in EFS in 2L aNHL flails Novartis’ aspirations of market expansion in this therapy area. Earlier, the company had reported positive results in R/R follicular lymphoma from the registrational Phase 2
ELARA trial; submissions are expected in H2 2021. 
In June, Gilead and BMS reported statistically significant improvements in EFS (primary endpoint) in 2nd line in similar settings for their CAR-T therapies. Gilead’s
Yescarta demonstrated 40% improvement in EFS in the ZUMA-7 trial with potential sBLA/MAA filings in 2H21. BMS’ Breyanzi also met the primary endpoint of EFS in TRANSFORM trial. All three CAR-Ts are approved for 3L+ DLBCL, although Breyanzi in the new entrant in this space.
Laurent Flamme, an analyst with ZKB, noted, “With a positive outcome, the consensus for peak sales would probably have gone above $2 billion from currently a little over $1 billion. With the approved indications, however, $1 billion in peak sales is still possible.
Collated by : Shilpa Rawal, PhD
Drug Approvals
FDA Approves TIBSOVO® (ivosidenib tablets) in IDH1-Mutated Cholangiocarcinoma
"Servier has been focused on exploring the significant potential of inhibiting mutant IDH enzymes as a novel approach to treating cancers with high unmet needs, including cholangiocarcinoma," said David K. Lee, CEO, Servier Pharmaceuticals. "We are proud to bring to patients the first and only targeted therapy for previously treated IDH1-mutated cholangiocarcinoma. We are grateful to the patients, caregivers, investigators and study teams who made this achievement possible through their participation in the ClarIDHy clinical trial."
European Commission Approves Minjuvi(R) (tafasitamab) + Lenalidomide for the Treatment of Adults with R/R DLBCL
"People living with relapsed or refractory DLBCL in the EU have historically had limited treatment options and a poor prognosis. However, with the EC's approval of Minjuvi, eligible patients now have a new and much needed treatment option," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We will now focus our efforts on working with individual countries in Europe to provide people access to this new treatment."
 Click here for more Drug Approvals
Regulatory News

US accelerated approval for Tecentriq® + Abraxane® in PD-L1+ve mTNBC withdrawn
“TNBC remains the most challenging type of breast cancer to treat, which makes the decision to withdraw so difficult for us, as patients have had this medicine as an important option for more than two years,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We appreciate the opportunity to have been able to help people with mTNBC in the US with Tecentriq through the accelerated approval process, which has brought many significant and novel therapies to patients. We remain dedicated to finding meaningful treatments for people living with this aggressive disease and will continue to study Tecentriq in mTNBC.”

Trial Results
Leronlimab-induced CTC Decrease associated with a 400%-660% increase in mPFS/12-month PFS and a 570%-980% increase in mOS/12-month OS
Scott Kelly, M.D., CytoDyn’s Chief Medical Officer and Chairman of the Board, commented, “We are delighted with the results of both mPFS and mOS when compared to the Standard of Care treatment for mTNBC across Emergency Use, Compassionate Use, mTNBC, and our Basket Trial. We anticipate the demand for new therapeutic options with limited toxicity and enhanced convenience for the patient to grow exponentially over the next decade. We believe this is further evidence that leronlimab has a promising role in the future of oncology to help alleviate the burden of cancer on patients and their loved ones. We are exploring opportunities to enhance our oncology platform through pharmacological partnerships, academic partnerships, and research on combining synergistic benefits of leronlimab in the tumor microenvironment.”
Trial/Program Status
Ph 1b Trial completed and Ph 2 initiated for CPI-613® (devimistat) + Gemcitabine and Cisplatin in Patients with Biliary Tract Cancer
“We are extremely excited and gratified to have completed Phase 1b and to be able to advance to the next phase (Phase 2),” said Sanjeev Luther, President and CEO of Rafael Pharmaceuticals. “Advanced biliary tract cancer is a rare and aggressive cancer with a 5-year survival rate of less than 5%, and the continuation of the trial aligns with our mission to help patients with significant unmet medical needs.”
Ph 2 INTR@PID BTC 055 study evaluating bintrafusp alfa with gemcitabine plus cisplatin in the first-line treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) to be discontinued as the study is unlikely to achieve the primary objective of overall survival. No new safety signals were identified.
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD 
Genes and Therapy
Shape Therapeutics collaborate with Roche to advance RNA technologies in gene therapy
On 24th August, Shape Therapeutics announced that it has entered into strategic research collaboration with Roche to advance the gene therapy space.  Shape Therapeutics will utilize its proprietary RNA editing platform RNAfix™ and potentially leverage its AAV (adeno-associated viruses)-based RNA editing technology platform, AAVid™ for next-generation tissue-specific AAVs for the development of gene therapy for certain targets in the areas of Alzheimer’s disease, Parkinson’s disease, and rare diseases.
Lysogene announces first patient dosed with LYS-GM101 for the treatment of GM1 gangliosidosis
Lysogene announced the dosing of first patient in the United States with its investigational gene therapy, LYS-GM101 for the treatment of GM1 gangliosidosis. The NCT04273269 clinical trial is a multi-center, single-arm, two-stage adaptive-design study evaluating the intracisternal delivery of a recombinant adeno-associated virus vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene (GBL1). GM1 gangliosidosis is a fatal autosomal recessive disease caused by mutations in the GLB1 gene leading to accumulation of GM1 ganglioside in neurons resulting in progressive neurodegeneration. No treatment has been approved so far for this disease.
MedNess HealthIT
Lung cancer screening made non-invasive using AI
Lung cancer happens to be one of the subtypes of malignant diseases where an early detection is rare, but can tremendously improve patient survival. Only less than 6 percent pf high risk individuals go through the low-dose computed tomography screening that has the potential to save thousands of lives. Exposure to radiation, cases of false positive, and aversion towards invasive techniques remain as the main reason for the lower level of screening. A novel artificial intelligence blood testing technology developed by Johns Hopkins Kimmel Cancer Center shows a new avenue to detect lung cancer at an early stage. The technique called DELFI (DNA evaluation of fragments for early interception) is designed to identify unique patterns in the fragmentation of DNA shed from cancer cells within the bloodstream. In a study that utilized 796 individual blood samples from Denmark, the Netherlands, and the United States, the AI program was successful in differentiating between presence or absence of lung cancer.  According to the lead author of the study Dimitrios Mathios  “It is clear that there is an urgent, unmet clinical need for development of alternative, noninvasive approaches to improve cancer screening for high-risk individuals and, ultimately, the general population.” According to him, “We believe that a blood test, or ‘liquid biopsy,’ for lung cancer could be a good way to enhance screening efforts, because it would be easy to do, broadly accessible and cost-effective.” By using machine learning tools, the study identified abnormal patterns in DNA sequence within the cell-free DNA released in the blood stream by dead or dying cells. This study of “fragmentome” is a low-cost technology that reliably differentiated between cancer developing population by identifying a wide variation in their fragmentome profiles, while those who didn’t have cancer had consistent fragmentome profiles. 
Collated by: Debarati Banik, PhD
MedNess Business
Onco-News
Pfizer to Acquire Trillium Therapeutics Inc.
“Today’s announcement reinforces our commitment to pursue scientific breakthroughs with the addition of potentially best-in-class molecules to our innovative pipeline,” said Andy Schmeltz, Global President & General Manager, Pfizer Oncology. “The proposed acquisition of Trillium builds on our strong track record of leadership in Oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our deep experience in understanding the science of blood cancers, along with the diverse knowledge base we have developed across our growing hematology portfolio of eight approved and investigational therapies, provide us with a foundation to advance these important potential medicines to patients who need them.”
Bolt Biotherapeutics and Innovent Biologics Announce Collaboration to Develop Three New Oncology Boltbody™ ISAC Programs
"Innovent is a leader in the development of innovative antibody therapeutics for the treatment of cancer, with advanced research and development teams and an expanding commercial infrastructure in China. We look forward to collaborating with Innovent on the development of novel ISAC anti-cancer therapeutic candidates,” said Randall Schatzman, Ph.D., CEO of Bolt Bio. “Our preclinical and early clinical studies have demonstrated the safety and efficacy of the ISAC approach and the benefits of stimulating both the innate and adaptive arms of the immune system in the fight against cancer.”
 Collated by: Richa Tewari, PhD 
BioPharma and MedTech
Moderna Founder Flagship's next big fundraiser is $440M for Laronde’s programmable 'eRNA'
The biotech investor behind Moderna and Denali, Flagship Pioneering, raises $440M on August 30th, 2021, for even more audacious startup Laronde, to pursue a programmable RNA platform. The long non-coding RNA construct can theoretically offer more durable therapeutic benefits than current or next-gen mRNA technology. Endless RNA™, or eRNA, was invented at Flagship Labs and is a new class of synthetic, closed-loop RNA. Because eRNA has no free ends, it is not recognized by the immune system and is very stable, enabling a long duration of protein expression. In addition, eRNA can serve protein-coding and non-protein-coding functions, and its protein translation capabilities are completely modular - switching an eRNA “protein sequence cassette” enables the expression of a different protein or multiple proteins that can be tuned as needed on an application-by-application basis. The biotech has previously said could roll out 100 marketed drugs or drug programs in 10 years.
Just within three months of its launch in May, Laronde draws much attention to its ambitious project. "Endless RNA represents a whole new approach to making medicines and treating disease," said Diego Miralles, M.D., Chief Executive Officer of Laronde and CEO-Partner at Flagship Pioneering. "Laronde is creating a new class of drugs that can be programmed to persistently express proteins in the body, is redosable, and can be administered through simple delivery mechanisms, resulting in highly tunable protein levels. The therapeutic possibilities enabled by eRNA are vast with the potential to greatly improve global human health. Having assembled such a knowledgeable and committed group of investors gives us the ability to not only advance this powerful technology platform but also build a transformative company to support our bold vision."
Laronde targeting to start supply clinical materials next year and possibly becoming public in near future. To keep up with the exceptional growth, Laronde is hiring new team members to build internal capacity and keeping options open for potential partnerships with Big Pharma.
Novartis’s Antibody for Obesity gets $70M funding from Atlas + Medicxi
Versanis Bio launched Tuesday, August 31st 2021 with $70 million from Atlas and Medicxi to offer a stable GLP-1 diabetes drug. Their Lead candidate is the Bimagrumab, an in-licensed Novartis drug originally targeting muscle weakness, gearing up for a Phase II study in obesity. The poor safety and efficacy track records of previous anti-obesity drugs and the lack of compelling targets for drug discovery delayed any major progress in treatment strategy. Bimagrumab may end the decades-long failures in the obesity field with some major progress.
Bimagrumab is a highly potent, first-in-class, fully human monoclonal antibody to the activin type II receptors that block the binding of ligands including activin A and myostatin. Bimagrumab has been studied by Novartis in more than a dozen controlled clinical trials that enrolled more than 1,500 people.
Dr. Mark Fishman, Co-Founder of Aditum Bio and member of the Versanis Bio Board of Directors said, “As people age, loss of muscle mass makes it even harder to lose weight. All existing obesity treatments risk further loss of muscle, together with fat. Bimagrumab is a unique therapy that builds muscle while markedly reducing fat, providing a potential breakthrough in the obesity epidemic.” This is an efficacy profile more in line with improving clinical outcomes and lowering risk factors than other drugs that target weight alone. Versanis is working to re-manufacture the drug for the mid-stage test as well as expand the potential patient population beyond just diabetes while also working on developing a more user-friendly subcutaneous application.
Click here for more on mergers, acquisition and business news
 Collated by: Darpan Chakraborty
Editors' Desk
Richa Tewari, PhD
Oncology News
Shilpa Rawal, PhD
Onco I-Analyse
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
Business Review
Debarati Banik
HealthIT

 
Darpan Chakraborty
Social Media Manager
BioPharma News
Nisha Peter, PhD
Managing Editor
Abhi Dey
Consulting Editor
Rinki Saha
BioPharma News
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing Editor
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Content Editors: Richa Tewari , Esha SehanobishRinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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