Business of Biotech Shorts

  1. Ep. 254, Chapter 3: What's A Stop Codon Disease? With Michelle Werner 7/11/2025

    Welch and Werner discuss Alltrna's patient-first mindset and its practical implications for early-stage rare disease companies. Werner goes on to define the concept of a "stop codon disease" as a reclassification for patients with genetic diseases stemming from a premature termination codon (nonsense mutation). This reclassification, affecting approximately 10% of genetic diagnoses, could allow a single engineered tRNA therapy to address thousands of different life-threatening conditions, offering a universal solution instead of a disease-by-disease approach. Alltrna leverages AI and machine learning to navigate the vast combinatorial space of tRNA designs, optimizing their sequence and chemical modifications for enhanced activity and stability.

  2. Ep. 254, Chapter 2: Why tRNA? With Michelle Werner 7/11/2025

    Alltrna's tRNA technology offers unprecedented ability to universally restore protein function across diverse disease models, regardless of affected gene, protein, or mutation location. For investors, Werner emphasizes the immense unmet need in genetic diseases, explaining how tRNA's universal approach to common nonsense mutations provides a compelling "reason to believe" backed by preclinical and now in vivo data. She highlights the company’s plan to utilize basket trials, a strategy common in oncology, to simultaneously its therapies simultaneously across multiple rare diseases sharing common mutations —not only optimizing development, but also unlocking value in ultra-rare diseases often overlooked due to small individual patient populations.

  3. Ep. 254, Chapter 1: Michelle Werner, Alltrna 7/11/2025

    Life Science Leader Chief Editor Ben Comer, joined by Advancing RNA Editorial and Community Director Anna Rose Welch, interviews Michelle Werner, CEO of Alltrna, which develops transfer RNA (tRNA) oligonucleotide therapies. Werner joined Alltrna following her son's diagnosis with Duchenne muscular dystrophy in 2020. She was drawn to the company’s unique platform, which aims to use a single engineered tRNA to address numerous different diseases, a significant departure from the one-disease-at-a-time approach of modalities like gene therapy. Werner also discusses the transition from a commercial role to leading a biotech startup, particularly the challenges of fundraising and managing a team of scientists.

  4. Ep. 253, Chapter 4: Infectious Disease + Oncology with Mark Eisner, MD 7/11/2025

    Vir Biotechnology's oncology strategy centers on overcoming the toxicity of unmasked T-cell engagers in solid tumors using the company’s PRO-XTEN™ masking platform. Vir currently has three clinical-stage programs: a HER2-directed T-cell engager for various HER2-positive tumors, a PSMA-targeted program for metastatic castration-resistant prostate cancer, and an EGFR-targeting TCE for multiple tumor types. Dr. Eisner stresses that masking technology allows for effective tumor killing with minimal toxicity. In 2025 and 2026, Vir's top goals include pivotal trials for hepatitis delta, continuing dose escalation for HER2 and PSMA programs, initiating the EGFR program, and identifying a partner for global development of the company’s hepatitis B functional cure program.

  5. Ep. 253, Chapter 3: Addressing Hepatitis Delta with Mark Eisner, MD 7/11/2025

    Hepatitis delta, a rare but severe liver disease that progresses rapidly, requires co-infection with hepatitis B. Hepatitis delta currently has no approved therapies in the U.S., though bulevirtide is used in Europe despite limited efficacy. In partnership with Alnylam Pharmaceuticals, Vir is poised to begin a Phase 3 trial for its combination regimen of tobevibart and elebsiran, which researchers believe can achieve complete viral suppression in most patients. Dr. Eisner emphasizes that partnerships are vital for biopharma companies like Vir to leverage scientific innovation and access global commercialization capabilities.

  6. Ep. 253, Chapter 2: The Art Of The Biotech Pivot with Mark Eisner, MD 7/11/2025

    Dr. Eisner explains how Vir’s Technology’s pivot from infectious disease to include oncology is more substantial than a large company reshuffling its portfolio, highlighting the thematic connection through the immune system and the foundational role of antibody engineering at Vir. He also details Vir's two distinct platforms: the dAIsY™ platform, an AI-driven tool for accelerating and optimizing antibody engineering, and the PRO-XTEN™ platform, a masking technology for T-cell engagers designed to improve efficacy and safety. Both platforms are considered complementary and are continuously refined.

  7. Ep. 253, Chapter 1: Mark Eisner, MD & Vir Biotechnology 7/11/2025

    Chief Editor of Life Science Leader and Host of The Business of Biotech, Ben Comer, and EVP and CMO at Vir Technology, Mark Eisner, MD, discuss Eisner’s career transition from academic medicine to product development and now his role at Vir. Dr. Eisner elaborates on Vir's strategic pivot to prioritize hepatitis programs and acquire Sanofi's masked T-cell engager platform. He also shares his leadership philosophy, which emphasizes patient focus and colleague mentorship in a collaborative biotech environment.

  8. Ep. 252, Chapter 5: From Rare To Large Indications 7/8/2025

    While Alnylam is well-equipped for rare and specialty conditions, broader public health issues such as hypertension and, potentially, Alzheimer’s, necessitate a shift in company mindset and a different commercialization approach. Alnylam’s strategic partnership with Roche for Zilebesiran will leverage the latter’s experience in CNS conditions and help to build Alnylam's capabilities for future large-scale opportunities. For 2025, Alnylam's top priorities include the launch of Amvuttra for cardiomyopathy and strengthening the company’s foundational commercial capabilities, such as AI, data generation, value-based agreements, and omnichannel marketing.

  9. Ep. 252, Chapter 4: Value-Based Contracts with Tolga Tanguler 7/8/2025

    Tanguler states Alnylam Pharmaceuticals’ approach to value-based contracts emphasizes resilience and long-term commitment. For example, in ultra-rare diseases, Alnylam offers cost predictability and, for its transthyretin amyloidosis (TTR) franchise, contracts are tied to clinical outcomes, wherein Alnylam provides rebates if patients don't achieve anticipated result. Alnylam also actively supports better non-invasive forms of patient diagnosis for rare diseases through increased awareness, collaboration with genetic testing partners, and addressing bottlenecks in the diagnostic value chain.

  10. Ep. 252, Chapter 3: Global Expansion Of RNAi with Tolga Tanguler 7/8/2025

    Alnylam Pharmaceuticals has expanded its footprint to more than 60 markets, with nearly half of its revenue generated outside the U.S. —diversifying the company’s revenue and enabling it to capitalize on region-specific opportunities. Tanguler explains why Alnylam’s commercialization approach involves categorizing markets by archetype (e.g., developed vs. distributor-led) rather than strict geography. He also speaks about how the company decides between direct presence and distribution partners, as well as the principles that guide Alnylam’s pricing strategy to maximize patient access.