CELL AND GENE THERAPY

Imara Announces Primary Endpoint Change in the Ardent Phase 2b Clinical Trial of Tovinontrine (IMR-687) in Sickle Cell Disease

Imara | November 22, 2021

Imara Announces Primary Endpoint Change in the Ardent Phase 2b Clinical Trial of Tovinontrine (IMR-687) in Sickle Cell Disease
Imara Inc. a clinical-stage biopharmaceutical company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare inherited genetic disorders of hemoglobin and other serious diseases, today announced a change to the primary endpoint for the Ardent clinical trial, a Phase 2b study of tovinontrine (IMR-687) in patients with sickle cell disease (SCD), based on the recommendation of the U.S. Food and Drug Administration (FDA).

Imara requested feedback from the FDA on the draft statistical analysis plan (SAP) for the Ardent trial in which fetal hemoglobin (HbF) response was the primary endpoint and annualized rate of vaso-occlusive crises (VOCs) was the key secondary endpoint. In reviewing the Ardent draft SAP and prior to any database lock for analysis, the FDA recommended that Imara change the primary endpoint to be annualized rate of VOCs. HbF response will continue to be evaluated as a key secondary endpoint. The endpoint revisions do not affect the conduct of the trial or operational aspects of the study. As part of its recommendation, the FDA suggested further interactions regarding the revised SAP and engagement on the potential of the current program for regulatory decision-making.

We welcome the FDA’s recommendations and are in the process of changing the primary endpoint of the Ardent trial to be annualized rate of VOCs and moving HbF response to be a key secondary endpoint. A reduction in VOC rate is an established approval endpoint, and we are engaging the FDA further on this and related topics, including possible streamlined paths to registration.


 Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara

Dr. Ballal continued, “In light of this endpoint revision, the previously planned fourth quarter interim analysis will no longer occur. That interim analysis had been designed to have a focus on safety and pharmacodynamic biomarkers, including HbF, but did not include a review of VOCs. The first review of data from the Ardent trial, including annualized VOC rate, will be conducted when all subjects have completed assessment at Week 24 or terminated early, and is planned for the first quarter of 2022, subject to our upcoming discussions with the FDA. Final data analysis from the Ardent trial remains on track for the second half of 2022. In June 2021, we reported promising data from our Phase 2a and open label extension clinical trials in SCD that demonstrated reduced annualized rates of VOCs in patients treated with tovinontrine versus placebo. We expect to present updated 12-month VOC data from our ongoing Phase 2a open label extension clinical trial at the American Society of Hematology Annual Meeting in December 2021.”

About the Ardent Phase 2b Clinical Trial
The Ardent Phase 2b clinical trial is a fully-enrolled, global, randomized, double-blind, placebo-controlled, multicenter study with approximately 115 adult patients with sickle cell disease (SCD) enrolled. The planned primary efficacy objective will be to evaluate the annualized rate of vaso-occlusive crises (VOCs) in patients dosed with tovinontrine (IMR-687) as compared to placebo. A key secondary endpoint will be to evaluate the proportion of all patients with fetal hemoglobin (HbF) response, defined as an absolute increase from baseline of at least 3% in HbF, as compared to placebo. Additional endpoints include the evaluation of the effect of tovinontrine versus placebo on other VOC-related outcome measures, HbF-associated biomarkers, markers of red blood cell hemolysis, white blood cell adhesion markers and quality of life measures over the course of a one-year treatment period.

The FDA has granted Orphan Drug, Fast Track and Rare Pediatric Disease designations and the European Commission has granted Orphan Drug designation for tovinontrine for the treatment of SCD.

About Tovinontrine (IMR-687)
Tovinontrine is a highly selective and potent small molecule inhibitor of phosphodiesterase-9 (PDE9). PDE9 selectively degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology and hemoglobin production in red blood cells. Lower levels of cGMP are found in people with sickle cell disease (SCD) and beta-thalassemia and are associated with reduced blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide mediated vasodilation. Blocking PDE9 acts to increase cGMP levels, which is associated with several benefits including the potential reactivation of fetal hemoglobin (HbF), a natural hemoglobin produced during fetal development. Increased levels of HbF in RBCs have been demonstrated to improve symptomology and substantially lower disease burden in both patients with SCD and patients with beta-thalassemia.

About Sickle Cell Disease
Sickle cell disease (SCD), a hemoglobinopathy, is a rare inherited red blood cell disorder. The disease causes structural abnormalities in hemoglobin that cause red blood cells to become inflexible and elongated, ultimately blocking blood flow to organs, which can lead to vaso-occlusive crises (VOCs). SCD is characterized by debilitating pain, progressive multi-organ damage and early death. The global prevalence of SCD is estimated to be approximately 4.4 million patients, including an estimated 100,000 patients in the United States and 134,000 patients in the European Union.

About Imara
Imara Inc. is a clinical-stage biotechnology company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare inherited genetic disorders of hemoglobin and other serious diseases. Imara is advancing tovinontrine (IMR-687), a highly selective, potent small molecule inhibitor of PDE9 that is an oral, potentially disease-modifying treatment currently in clinical development for sickle cell disease and beta-thalassemia and preclinical development for heart failure with preserved ejection fraction, or HFpEF. Imara is also advancing IMR-261, an oral activator of nuclear factor erythroid 2–related factor 2, or Nrf2. 

Cautionary Note Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to (i) the Company’s plans to change the primary and secondary endpoints for the Ardent Phase 2b clinical trial of tovinontrine (IMR-687), (ii) the timing for reporting of additional data from the Ardent Phase 2b and open label extension clinical trials of tovinontrine in patients with sickle cell disease and (iii) the Company’s planned discussions with the FDA regarding the regulatory pathway for tovinontrine. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the impact of extraordinary external events, such as the risks and uncertainties resulting from the impact of the COVID-19 pandemic on the Company’s business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities and ability to readout data from the Ardent Phase 2b and open label extension clinical trials of tovinontrine in sickle cell disease; the Company’s ability to advance the development of tovinontrine under the timelines it projects in current and future clinical trials, demonstrate in any current and future clinical trials the requisite safety and efficacy of tovinontrine; and other factors discussed in the “Risk Factors” section of the Company’s most recent Quarterly Report on Form 10-Q, which is on file with the Securities and Exchange Commission and in other filings that the Company makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.


Spotlight

Biotech crop highlights in 2015. This infographics related to the  Biotechnolgy.   

Spotlight

Biotech crop highlights in 2015. This infographics related to the  Biotechnolgy.   

Related News

RESEARCH

Quantgene Demonstrates Game-Changing Sequencing Precision in GENES, A Leading Scientific Journal

Quantgene | June 08, 2021

Quantgene, biotechnology, cloud, and AI company located in Santa Monica, CA, and Berlin, Germany, has demonstrated the most exact gene sequencing yet published in the industry, as shown in the February edition of GENES, a major scientific journal in medical genomics. "Precision Genomics is revolutionizing medicine, but it is being hampered by a lack of rapid, accurate, and easily accessible technology," said Jo Bhakdi, CEO of Quantgene. "Today, the protection of human life is dependent on the advancement of precision genomics, and we are excited to open a new chapter in genomic testing and less invasive cancer screening." DEEPGENTM reduced error rates on Illumina NovaSeq platforms hundreds of times by integrating new chemistry with large-scale cloud processing, mathematically enhanced error reduction, and statistically optimized genomic mapping, signaling an innovative approach ahead for cancer testing. Quantgene's latest innovation is a significant step forward in evidence-based healthcare and precision medicine. Quantgene's DEEPGEN technology was thoroughly investigated in its peer-reviewed publication, which included a series of technical validations. According to the publication, the system detects somatic variations in DNA fragments with an accuracy of more than 1 in 1000 fragments, with high repeatability and very low false-positive results. This degree of accuracy has previously only been proven in a peer-reviewed setting for systems that examined a small number of genomic regions. DEEPGEN's technology covers around 70,000 locations and includes a wide range of FDA-approved cancer targets. The results of Quantgene represent a significant advance in the identification of cancer signals in the blood using liquid biopsy and next-generation sequencing technology. Liquid biopsy can be a less invasive and more accurate method of diagnosing different forms of cancer. In oncology, it may also be used to aid physicians in early cancer detection, companion diagnostics, and identifying minimum residual disease. "This is a crucial step forward in precision medicine. Quantgene provides the industry with a more powerful tool to diagnose cancer and other serious diseases earlier than ever before by achieving single-molecule sequencing precision ", said Jo Bhakdi, CEO of Quantgene. About Quantgene Quantgene has emerged as a technical leader in single-molecule precision sequencing over the last six years. To better protect patients from cancer, the company combines deep genomic, cloud, and AI technologies with innovative preventative medicine solutions. Its objective is to increase the healthy human lifespan by ten years within the next ten years.

Read More

Cedilla Therapeutics Completes $82.6M Series B Financing

Cedilla Therapeutics | October 25, 2021

Cedilla Therapeutics a biotechnology company bringing a new dimension to precision oncology, today announced that it has raised an additional $25 million in an expansion of its Series B financing, bringing the total amount raised to $82.6 million. The oversubscribed Series B expansion includes new investors RA Capital Management, Janus Henderson Investors, Woodline Partners LP and Logos Capital, along with participation from existing investor Third Rock Ventures.“We are grateful for the support from our new and existing investors, which reflects the promise of our novel approach to conditionally modulating proteins as well as the unique potential of our lead programs, inhibitors against TEAD and CDK2, two critical but historically undruggable targets,” said Alexandra Glucksmann, Ph.D., President and Chief Executive Officer of Cedilla Therapeutics. “With this financing, we plan to accelerate and expand our development efforts by progressing our most advanced programs toward the clinic while continuing to invest in ongoing discovery efforts against additional high value cancer targets.” Proceeds from the financing will support Cedilla’s continued growth and development of its two lead programs, an inhibitor of TEAD for the treatment of solid tumors, such as mesothelioma and certain squamous cell carcinomas, and a highly selective inhibitor of CDK2/Cyclin E for the treatment of multiple tumor types, including CDK4/6-resistant breast cancer, ovarian, uterine, stomach and esophageal cancers. The company plans to initiate investigational new drug application-enabling studies for the TEAD program in the first half of 2022 and for the CDK2 program in the second half of 2022. In conjunction with the financing, Jake Simson, Ph.D., Partner at RA Capital Management, joins Cedilla’s Board of Directors. Dr. Glucksmann continued, “We are pleased to welcome Jake to our Board of Directors. He brings a wealth of experience advising companies from the earliest stages of company formation through their maturation into fully integrated biopharmaceutical organizations. We look forward to his many contributions as we continue to grow Cedilla into a clinical-stage organization with a robust and growing portfolio of product candidates.” “Cedilla brings a new dimension to precision oncology by conditionally modulating proteins in their functional state Preclinical data generated to-date suggest that Cedilla’s lead programs may challenge historical perceptions of TEAD and CDK2 as undruggable targets and could offer patients new options that would be well-tolerated and extremely effective. In addition, Cedilla’s approach, based on a deep understanding of how the cellular context modulates protein activity, could deliver superior inhibitors against a range of other key cancer drivers. I look forward to partnering with the team with the aim to deliver a broad portfolio of small molecule medicines, each with potential profound benefit to patients.” Jake Simson, Ph.D., Partner at RA Capital Management About Cedilla Therapeutics Cedilla Therapeutics is bringing a new dimension to precision oncology. We have discovered new ways to selectively inhibit oncogenic drivers with small molecules that conditionally modulate proteins in their functional state. Our conditional inhibitors are unlocking critical and elusive cancer targets including TEAD and CDK2. We are a driven and patient-focused team. x

Read More

CELL AND GENE THERAPY

Valneva and IDT Biologika Announce Collaboration for Production of Inactivated COVID-19 Vaccine VLA2001

Valneva SE, IDT Biologika | November 30, 2021

Valneva SE, a specialty vaccine company, and IDT Biologika announced their collaboration for the production of Valneva’s inactivated COVID-19 vaccine candidate VLA2001. This follows last week’s announcement that Valneva signed an Advance Purchase Agreement with the European Commission to supply up to 60 million doses of VLA2001, over two years. Under the collaboration, IDT Biologika will produce VLA2001’s drug substance at its Biosafety Level 3 facilities in Dessau-Roßlau, Germany, in addition to Valneva’s manufacturing site in Livingston, Scotland. “IDT is a well-established partner within Valneva’s manufacturing network. As such we are extremely pleased to extend this partnership to supply VLA2001. This collaboration will help ensure our inactivated vaccine is available for rapid deployment as we continue to believe that our differentiated vaccine candidate can make an important contribution to the global fight against the COVID-19 pandemic.” Thomas Lingelbach, Chief Executive Officer of Valneva Dr. Jürgen Betzing, Chief Executive Officer of IDT Biologika, added, “This is great news for our company. This assignment shows the importance of the role played by IDT in the fight against COVID-19. It is a great achievement and demonstrates the trust that Valneva has placed in us and our employees. The expansion of our production capacity combined with our expertise were key factors in the choice of IDT.” Valneva has continued to review its manufacturing strategy following discussions with the UK Government in the summer and again after the termination of the UK contract in September 2021. Valneva plans to operate a combination of external and internal production of VLA2001 and will further review its manufacturing plans based on demand. The Company’s sites in Livingston, Scotland and Solna, Sweden will continue to form part of the Company’s core manufacturing strategy. Valneva reported positive Phase 3 results for VLA2001 in October 20211. Delivery of the vaccine in Europe is currently expected to begin in April 2022, subject to approval by the European Medicines Agency which is expected to start a rolling review of VLA2001 shortly. About VLA2001 VLA2001 is currently the only whole virus, inactivated, adjuvanted vaccine candidate against COVID-19 in clinical trials in Europe. It is intended for active immunization of at-risk populations to prevent carriage and symptomatic infection with COVID-19 during the ongoing pandemic and potentially later for routine vaccination including addressing new variants. VLA2001 may also be suited for boosting, as repeat booster vaccinations have been shown to work well with whole virus inactivated vaccines. VLA2001 is produced on Valneva’s established Vero-cell platform, leveraging the manufacturing technology for Valneva’s licensed Japanese encephalitis vaccine, IXIARO®. VLA2001 consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018. This adjuvant combination has consistently induced higher antibody levels in preclinical experiments than alum-only formulations and shown a shift of the immune response towards Th1. CpG 1018 adjuvant, supplied by Dynavax Technologies Corporation (Nasdaq: DVAX), is a component of the US FDA- and EMA-approved HEPLISAV-B® vaccine. The manufacturing process for VLA2001, which has already been upscaled to final industrial scale, includes chemical inactivation to preserve the native structure of the S-protein. VLA2001 is expected to conform with standard cold chain requirements. About Valneva SE Valneva is a specialty vaccine company focused on the development and commercialization of prophylactic vaccines for infectious diseases with significant unmet medical need. The Company takes a highly specialized and targeted approach to vaccine development and then applies its deep understanding of vaccine science to develop prophylactic vaccines addressing these diseases. Valneva has leveraged its expertise and capabilities both to successfully commercialize two vaccines and to rapidly advance a broad range of vaccine candidates into and through the clinic, including candidates against Lyme disease, the chikungunya virus and COVID-19. About IDT Biologika IDT Biologika is an innovative biotech company with a successful history dating back 100 years. On the basis of modern technologies and high levels of expertise, we support customers in the development and manufacture of innovative virus vaccines, gene and immune therapy products as well as biologics employed worldwide as protection against diseases. German sites are the BioPharmaPark in Dessau-Roßlau and Magdeburg. In the US, the IDT Corporation has a manufacturing site for clinical test samples in Rockville, Maryland.

Read More