282: When Your Delivery Vehicle Contains a Membrane Protein: CMC Decisions With No Regulatory Precedent with Jitendra Kumar - Part 2

Your active ingredient is the nucleic acid. So why does a proteolipid vehicle filing include viral clearance studies, stability data and full characterisation of a membrane protein that is not the drug? Because that protein sits on the particle surface, and a component nobody has filed before is the agency's problem regardless of what you call it. Proteolipid vehicles (PLVs), the platform Jitendra Kumar works on as Lead Scientist for Chemistry and Process Development at Entos Pharmaceuticals, represent a novel frontier in drug delivery, Instead of being taken up into an endosome and having to escape it, a PLV fuses with the cell membrane and releases cargo straight into the cytosol. That opens targets and patient groups that liver-tropic lipid nanoparticles and viral vectors have struggled to reach, and it leaves Kumar building a regulatory file with nothing on the shelf to copy. Highlights from the episode: Strategies for communicating novel technology with regulatory agencies and ensuring robust science-driven submissions (02:34) What differentiates the analytical characterization of PLVs compared to standard recombinant proteins or antibodies (04:03) The development plan and regulatory pathway towards clinical and commercial approval for their lead leptin therapy (05:35) The evolving role of advanced techniques—such as cryo-EM—in supporting regulatory filings and product understanding (06:56) Jitendra Kumar's career journey: from agricultural research in India to protein science and neurodegeneration, and how these experiences inform current PLV technology development (09:00) Challenges of early diagnostics and product development in neurodegenerative diseases (14:29) Decision-making differences and focus in academic versus industry biotech research (15:32) Practical advice on the importance of honest technology assessment, building networks, and understanding both strengths and weaknesses (16:16) Smart insight: A persistent challenge for groundbreaking delivery systems is the lack of established regulatory playbooks. Jitendra Kumar laid out a science-first approach: let data do the talking, supported by rigorous GLP toxicology studies and transparent communication with agencies. Regulatory bodies like Health Canada are receptive to innovation, provided that sponsors demonstrate safety, efficacy, and scientific rationale for any deviation from standard criteria. If this conversation got you thinking about how novel delivery vehicles reach the cell — and what it takes to carry one from bench through CMC, scale-up, and regulatory review — these four episodes go deeper: Episodes 125 - 126: How to Enhance Cell Engineering Using Mechanical Intracellular Delivery with Armon Sharei Episodes 231 - 232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann Episodes 89 - 90: Scale-Up Secrets: Cracking the Code of AAV Production with Ahmed Youssef Episodes 71 - 72: Effective Outsourcing: How Small Biotech Companies Can Thrive with Mark Melville Connect with Jitendra Kumar: LinkedIn: www.linkedin.com/in/jkumar2 Email: [email protected] Website: www.entospharma.com Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here Support the show