Annette Bak

Want to know how AstraZeneca's Irina Ramos and AbbVie's Sanjay Nilapwar are intensifying #biopharma processes and mapping their next #continuousmanufacturing steps? Then ask them! This talk, 6/11 at 11 AM ET, promises to be a good one, and it's less than a week away. Register here, at no charge, and get in on the conversation! https://lnkd.in/eZ4-WiJq

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OPCU - Partner Week: Biotech's developing large molecule drugs should attend, finding the right outsourcing partner is critical to drug development strategy! At OPCU events, get your questions answered and find out what you need to know within your selection process of working with CDMO partners, timing , capabilities and cultural fit can all be assessed at the Outsourced Pharma Capacity Update. Just Ask for a follow up meeting after the presentation!

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Terrific panel discussion about the right time and approach for bringing novel cell-based #genetherapies from the lab to the clinic. From the impact on #patients and families of speeding up development timelines, to the limitations of extrapolating safety and efficacy from the mouse model to humans, to the right number of different CRISPR-Cas 9 gene edited CAR~Ts to include in the same #clinicaltrial, to the appropriate benefit-risk trade-offs, to cost, coverage and reimbursement, and health equity considerations, this morning’s discussion provided a rich set of issues for FDA, the Centers for Medicare & Medicaid Services, sponsors, and patient advocates and providers to mull over.

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Biopharma Industry Gains Flexibility with FTC's Non-Compete Ban The Federal Trade Commission's (FTC) recent ruling prohibiting non-compete clauses in employment contracts presents a significant development for the biopharmaceutical industry. This landmark decision fosters greater professional mobility, enabling biopharma professionals to pursue diverse career opportunities and contribute their expertise across a wider range of organizations. This elimination of restrictive clauses empowers talented individuals to align their passions and skills with various biopharma companies, fostering a more dynamic and competitive industry landscape. The ability to freely leverage one's expertise across different entities can ultimately accelerate innovation and contribute meaningfully to advancements in healthcare and biotechnology. As the industry adapts to this evolving landscape, biopharma professionals have a unique opportunity to embrace this newfound freedom to explore, collaborate, and propel the future of biopharmaceuticals. Through this collective effort, we can make a significant and positive impact on global health. #Biopharma #CareerMobility #ProfessionalDevelopment

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The surge in approvals for #cellandgenetherapy (CGT) products offers hope for patients with chronic and #rarediseases that have long been without treatment options. The robust pipeline of innovative treatments presents compelling opportunities for investors, not only in early-stage ventures but also in midmarket and larger companies across the industry vertical. As the number of approved CGT products continues to rise, investors are increasingly interested in sectors such as raw materials, manufacturing equipment and services, and logistics. With the potential for substantial growth ahead, understanding the complexities and opportunities of the CGT market will be essential for investors seeking to capitalize on this development. 

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This review proposes a set of modifications to existing regulatory requirements for #mRNA products, based on a platform perspective for quality, manufacturing, preclinical, and clinical data. The authors address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, they propose considerations for self-amplifying mRNA, individualized oncology mRNA products, and mRNA therapeutics.  

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There is a new paper on DIA global, “The role of RWD & RWE in shaping global regulatory practices“, by Jeffrey Brown from TriNetX. It’s well written. I especially liked the “known unknowns” and “unknown unknowns” discussion, and “matching the expertise of RWE generator & reviewer”suggestion. Two comments: 1. FDA, EMA, PMDA were mentioned, NMPA was left out. In fact, seven RWD/E guidance were published by NMPA during the past years; NMPA has been a strong advocator of RWD/E. 2. RWE for regulatory consideration has a bright future with a rough path forward. So, for everyday practitioners, what are the suggestions between the miserable reality and bright future, especially for service providers, who need to deliver? That reminded me on an External Control Arm study a couple of years ago, where a “perfect” piece of evidence was not available, but we might be able to generate a chain of “good” evidences, combining both primary and secondary data. Is perfect the enemy of good for regulatory RWE studies?

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#FDA Oncology Center of Excellence (#OCE) will be quite active at incoming #ASCO2024. Link to OCE presentations, discussions and research findings to come at ASCO 2024: https://lnkd.in/gQS6HVp5. Few events that raise particular interest: -Case-based Panel: Multicancer Detection: Is It Ready for Prime Time? Title: The Regulatory Perspective: Hurdles to Overcome. OCE speaker: Jamie Brewer (presentation and panelist), 2:45-3:45 pm CT, Hall A, Friday May 31st -Education session: Integrating Immunotherapy into Early-Stage Lung Cancer. Title: Too Many Options: Assessing the Best Trial Designs. OCE speaker: Bernardo Goulart (presentation and panelist),  9:45-10:45 am CT, Hall B1, Sunday June 2nd -ASCO 2024 FDA Special Session: Improving Global Access to Cancer Therapies Through Regulatory Authority Collaboration. Richard Pazdur (moderator), Angelo de Claro (presentation and panelist), 11:30 am-12:45 pm CT, S100a, Monday June 3rd. More details about topics to be covered and panelists representing multiple regional regulatory authorities at https://lnkd.in/gmXrn4r8. #ASCO2024 #OCE #FDA #Cancer therapy #access #oncology trial design #lung cancer #oncology clinical strategy #medical affairs strategy

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Umoja Biopharma Announces Publication in Blood Highlighting Successful Generation of In Vivo CAR T-cells in Non-Human Primate Modeling First landmark, peer-reviewed publication of successful in vivo CAR T-cell data in an immune competent NHP model Data validate the VivoVec™ platform in a translationally relevant model and support its transition into human clinical testing, offering a potential paradigm shift in the field of CAR T-cell therapies Key Study Findings VivoVec particles (VVPs) incorporating CD80 and CD58 costimulation proteins exhibit enhanced capacity for in vivo CAR T-cell generation and produce CAR T-cells with increased antitumor functionality compared to those produced from VVPs displaying anti-CD3 scFvs alone. Combining the anti-CD3 scFv together with the ligand binding domains of CD80 and CD58 into a single multi-domain fusion (MDF) protein markedly augments the particles’ ability to bind, activate, and transduce T-cells. VVPs incorporating MDF compatible with NHP T-cell activation and costimulation potently generate anti-CD20 CAR T-cells in vivo, comprising up to 65% https://lnkd.in/eqsSTKjf

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The clinical NGS landscape continues to evolve, and the latest edition of our NGS DxBook offers insights into changes in the competitive landscape. Focusing on the use of #Illumina and #ThermoFisher platforms and assays in clinical oncology, Rishikesh noticed a few interesting trends since last year: 1. Diversity and Dominance in Gene Panels: Illumina leads in panel diversity and volume, leveraging an expansive range of third-party kits. Our data visualizes this dominance across various panel sizes including WES and WGS, and the impressive traction these approaches have gained in recent years. 2. Regional Dynamics and Market Shares: While ThermoFisher has carved a niche in smaller gene panels (1-52 genes), especially in Europe, Illumina continues to expand its footprint in larger panels, with a dominant position in the U.S. 3. Strategic Positions in a Competitive Field: Despite challenges in the stock market, Illumina's strategic partnerships with reagent and bioinformatics firms like Pillar and Velsera has solidified its entrenched market position, simplifying workflows and enhancing user experiences. Conversely, ThermoFisher’s investment in an integrated ecosystem with solutions like Ion Chef and Ion Reporter caters to labs seeking end-to-end automation. Feel free to reach out with questions! And remember: #NGSisUnstoppable

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Check out our paper in the Journal of Medicinal Chemistry: “Discovery of Clinical Candidate PF-06648671: A Potent γ-Secretase Modulator for the Treatment of Alzheimer’s Disease”. We are grateful to everyone at Pfizer who contributed to this program over the years – especially to Christopher am Ende, Todd Butler, and Doug Johnson who were instrumental in getting this manuscript over the finish line. For those of you in the drug hunting community who may not be familiar with the pharmacological distinction between γ-secretase inhibitors (GSIs) and γ-secretase modulators (GSMs), here is a brief summary: - γ-Secretase Inhibitors (GSIs): This older class of compounds binds to the active site (or to an allosteric site) on the presenilin subunit of the γ-secretase complex resulting in inhibition of the enzyme. In addition to blocking formation of all forms of amyloid beta (Aβ) peptides, this approach also inhibits processing of many other substrates (including the Notch receptor) that are critical for normal cellular functions. Several γ-secretase inhibitors were advanced into clinical trials for Alzheimer’s disease quite some years ago, but these trials were terminated due to on-target toxicity. - γ-Secretase Modulators (GSMs): These compounds have a very different pharmacological profile compared to the GSIs. GSMs also bind to the presenilin subunit, but at allosteric sites that are distinct from those of the inhibitors. Rather than inhibiting the enzyme, GSMs modulate the enzymatic function and change the processivity to reduce formation of the longer, insoluble and neurotoxic Aβ peptides (including Aβ42) while increasing formation of the shorter, more soluble peptides, Aβ37 and Aβ38. Meanwhile, total Aβ remains unchanged. Most importantly, this class of compounds does not inhibit Notch processing. As a result, GSMs may be an effective approach to selectively reduce formation of the toxic Aβ peptides while sparing normal enzymatic function (see introduction of the paper for more info along with relevant references). https://lnkd.in/enHskGYp

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The more we understand how #CellTherapies help patients, the better we will be able to develop safer, durable, and efficacious treatments! #TheMoreWeKnow "The immune system overreaction known as cytokine release syndrome (CRS), and neurologic toxicities are two well-known side effects of CAR-T treatment. Last week, regulators removed a requirement for clinicians to report serious cases of the side effects as part of its Risk Evaluation and Mitigation Strategies for Gilead’s treatments Yescarta and Tecartus." https://lnkd.in/efmXtYZ5

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Since 2015, Dana-Farber researchers have been participating in clinical trials that evaluate the use of bispecific antibodies for patients with non-Hodgkin lymphoma. Three bispecific antibody therapies have been FDA approved with more on the horizon. These are exciting new medicines that rally the immune system in a powerful way to fight blood cancers. But rolling out a new type of medicine is a project of its own. The experts at Dana-Farber who have been treating patients with these new medicines are now working on expanding their use. Philippe Armand, MD, PhD, chief of the Lymphoma Program, and Jennifer Crombie, MD, Reid Merryman, MD, and Christine Ryan, MD, physicians and clinical investigators in the Lymphoma Program, are using what they have learned as clinical investigators to run new trials to determine if these medicines could have benefits earlier in treatment, in combination with other therapies, or in other types of lymphoma. “The hope is that these drugs will help improve outcomes for patients with lymphoma,” says Crombie, who has been the principal investigator of a bispecific antibody trial for the past few years. Monoclonal antibodies treat cancer by binding to markers on cancer cells and rallying the immune system to destroy them. Bispecific antibodies are designed to recognize and bind to more than one cell marker. The bispecific antibodies approved for the treatment of B-cell non-Hodgkin lymphoma recognize CD20, a marker known to be on B cells, and CD3, a marker known to be on T cells, which are immune cells that can attack cancer cells. By binding to both, the bispecific antibody pulls the T cells closer to the cancerous B cells, increasing the chances that the T cells will recognize and kill the cancer. “Bispecific antibodies can be a powerful immune-based mechanism because of their dual binding properties,” says Crombie. These medicines are currently approved for use alone in patients with follicular lymphoma or diffuse large-cell lymphoma who have received three lines of treatment and need a new therapeutic option. Some patients may choose to try bispecific antibody therapy after CAR T-cell therapy. Others may opt to try bispecific antibodies before trying, or in lieu of, CAR T-cell therapy. Recommendations will vary depending on the type of lymphoma and other individual factors. These new therapies are administered via infusion or an injection under the skin. However, these immunotherapies can cause side effects that many centers are learning how best to manage. In clinical trials of bispecific antibodies, investigators noted side effects that are like those experienced by patients receiving CAR T-cell therapy. The reactions, however, are often less frequent and less severe. Learn more: https://lnkd.in/e4D8T2GG

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And another chapter in the #drugpricing debate for #genetherapies, touching on many hot-button #healthpolicy issues from #acceleratedapproval for gene therapies and the reliability of #surrogate #endpoints to #alternativepaymentmodels for #genetherapies and their #cost, #value, and benefit-risk-tradeoffs. This is certainly not a new debate, but one that is increasingly gaining attention given the growing number of cell and #genetherapies on the market and the robust pipeline. It does raise (at least) two issues for me: First, it is easy to forget the real-life impact of #accelerated approval on the #patients and families. On average, #accelerated approval shaves 4.5 years off the #drugdevelopment timeline by allowing FDA's approval decisions to be based on surrogate or intermediate clinical endpoints, rather than having to wait for traditional (validated) clinical endpoints. For neurodegenerative diseases in particular, it can take years or decades for the clinical endpoints to occur. Getting these products into the hands of clinicians earlier is huge - especially for #genetherapies with narrowly defined age limits. ELEVIDYS, the product at issue in this paper, is currently only approved for 4 and 5 year olds. How many children would have aged out of the chance for a potential cure (or something close to it) without accelerated approval? Second, nobody questions that one-time payments of $3.2 million are substantial costs for any #healthinsurance #payer. It has to be seen in the context of the direct and indirect costs averted over time, although health insurance portability means that in many cases the payer that realizes the cost is probably not the one that realizes the subsequent savings. Moreover, exactly how large the subsequent savings really are remains somewhat unclear given remaining questions around long-term safety and durability of effect. That makes #innovativepaymentmodels particularly important, allowing for some of the risks to be shared across insurance providers and with manufacturers. But the reality is that current data systems in the U.S.'s fragmented healthcare ecosystem and are woefully inadequate to generate the type of evidence needed to support meaningful and broadly applicable #outcomesbased #arrangements. I hope the policy debate around the price of current #genetherapies will evolve to one that provides tangible policy solutions and that truly places the patient at the center. What we need to move forward is centralization, standardization, and data sharing, led by the Centers for Medicare & Medicaid Services, to enable meaningful outcomes-based arrangements that simultaneously mitigate some of the economic risks associated with #genetherapies and provide the evidence to support accelerated approval through robust confirmatory evidence, so that this critical pathway will remain available to the life-altering #orphandrugs that need it. https://lnkd.in/euzyxV_a

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Safety. This, to me, is the most important question to be addressed today by the FDA advisory committee on Lykos’s NDA for MDMA. Based on the data they’ve presented - and what they’ve failed to present- they are likely to fare poorly on this area Discussion can be followed live here https://lnkd.in/gdv3ezgp

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Congratulations to Bristol Myers Squibb, BMS’ Augtyro Wins FDA Accelerated Approval for NTRK-Positive Solid Tumors Bristol Myers Squibb on Thursday announced that its tyrosine kinase inhibitor Augtyro (repotrectinib) was granted accelerated approval by the FDA for the treatment of NTRK-positive, locally advanced or metastatic solid tumors. Under the new indication, Augtyro can be used in patients aged 12 years and older whose disease has progressed after initial treatment. Augtyro can also be used in patients with no satisfactory alternative therapies or in those who are likely to suffer from “severe morbidity” due to surgical resection, according to the company. Under the FDA’s accelerated pathway and to keep Augtyro’s approval, BMS will need to run a confirmatory study to validate the clinical benefit of the drug in this indication and patient population. Nick Botwood, senior vice president of medical oncology at BMS, in a statement called Augtyro’s approval a “milestone” that “helps address this area of unmet need” and underscores the drug’s “clinical value for more people across multiple genetic markers.” “Previously, there was not an FDA-approved treatment option for NTRK-positive cancers that was studied in both TKI-naïve and TKI-pretreated patients across solid tumors,” Botwood said, noting that Augtyro can now provide these patients with an effective treatment option. The FDA’s approval of Augtyro is backed by data from the Phase I/II TRIDENT-1 trial, which enrolled patients who had been exposed to prior TKI treatment and those who were naïve to this drug class. A total of 15 different types of cancer were represented in the study. https://lnkd.in/e8eKHHvp

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🎤 uBriGene Presents Exclusive Sessions at SAPA 2024 @Philly CGT Annual Conference 🎤 🚀 We're thrilled to announce our participation at 2024 @Philly Cell and Gene Therapy Annual Conference with two exclusive sessions aimed at revolutionizing the field: 1️⃣ An Innovative Technology for High Yield and More Stable #CRISPR Guide RNA: Discover how our innovative approach of using in vitro transcription (IVT) in producing guide RNA (#gRNA) that can simplify the process while being more cost-effective and free of organic chemicals. Join us to delve into the future of precision gene editing. 2️⃣ How Could CDMO and Technology Innovations Make CGT Affordable: Dive into the intersection #CDMO of and technological advancements with uBriGene. Learn about our strategies to drive down costs without compromising quality or efficacy. Let's explore how cutting-edge technology can make #CellandGeneTherapy more accessible to all. 2024 @Philly Cell and Gene Therapy Annual Conference brings together the innovators and business leaders to foster collaborations and advance cell and gene therapy in the #GreaterPhiladelphia area. 💡 Join #uBriGene to be at the forefront of innovation and collaboration in the dynamic world of cell and gene therapy and let's make cutting-edge cell and gene technology more accessible!

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From an accelerated approval, Bristol Myers Squibb's KRAS-inh #KRAZATI obtains the nod for colorectal cancer (with Eli Lilly and Company's Erbitux (cetuximab)) https://lnkd.in/eRFiV9Fw "GlobalData recently predicted that the market for KRAS-targeting drugs in oncology could reach $4 billion by 2029, with Lumakras and Krazati accounting for around $1.4 billion of that total. Morningstar analyst Damien Conover said after the CRC approval that Krazati could become a $1 billion product, justifying BMS’ takeover of Mirati" 📈 As a #strategic milestone and growth potential standpoint, the treatment is only one of two on the market, representing a significant advancement in the treatment of this disease, particularly for patients with a specific genetic mutation. #BMS #Krazati #KRASinhibitors #CRC #Oncology #ColorectalCancer #RegulatoryAffairs #Pharma #Healthcare

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