Beyond Biotech - the podcast from Labiotech

Mark Kotter, founder of clock.bio and CEO of bit.bio, discusses the potential of using human pluripotent stem cells to reverse the harmful effects of time in our cells. The podcast covers the development of aging models, unbiased CRISPR screens, and the identification of gene candidates for cell rejuvenation. The goal is to extend health span by 20 years and create novel treatment approaches based on biomarkers of aging.

This week's podcast features Fred Aslan, CEO of Artiva Biotherapeutics, discussing the potential of natural killer (NK) cells in cancer treatment. They explore the challenges in developing NK cell therapy, the collaboration with AffiMed to enhance NK cell activity, upcoming milestones for the company in 2024, and the difficulties in finding participants for clinical trials in the biotech field.

Compared to the smallest mRNA molecule, which is 300 nucleotides long, the largest transfer RNAs (tRNA) is less than a third of the size at 76 nucleotides. Scientists at Alltrna are harnessing the unique biology of tRNAs to engineer a single tRNA medicine that could treat thousands of rare diseases that share the same genetic mutation. This year, Alltrna presented at ASGCT the first demonstration that an engineered, modified tRNA could recognize and correct, in vivo, a flawed mRNA instruction no matter where it occurred in the genome.Alltrna, which was founded in 2018 by Flagship Pioneering, recently announced it had raised $109 million in a Series B financing to advance the company’s platform and first drug candidates towards the clinic for a first indication in Stop Codon Disease.  Stop Codon Disease encompasses ​​thousands of rare and common diseases that arise from premature termination codons (PTC), also known as nonsense mutations, where the code for an amino acid has been mutated into a premature “stop” codon. This results in a truncated or shortened protein product with no or altered biological activity that causes disease. Approximately 10% of all people with a genetic disease have Stop Codon Disease, representing approximately 30 million people worldwide. Alltrna’s tRNA medicines can read these PTC mutations and deliver the desired amino acid, thereby restoring the production of the full-length protein.The company’s platform incorporates artificial intelligence and machine learning tools to ‘learn’ the tRNA language and deliver diverse, programmable molecules with broad therapeutic potential. This week, our conversation is with Alltrna CEO, Michelle Werner.To learn more about the topic, we invite you to read the following article:  Will tRNA therapy be the next big thing in genetic disease treatment?

Disease X, a concept shrouded in mystery, represents the unknown pathogens that could unleash future epidemics or pandemics. In the wake of recent global health crises, our understanding of the profound impact of those pandemics has deepened. On this week’s podcast, we have a conversation with Hamilton Bennett, who led Moderna’s mRNA-1273 COVID-19 vaccine development program team to the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic. Bennett is Moderna’s senior director of vaccine access and partnerships, and has unparalleled insights into the world of infectious diseases. In this in-depth discussion, Bennett talks about the origins of Disease X, the role of mRNA technology in tackling pandemics, and the importance of preparedness.Disease X was intended to be a placeholder name; it was adopted by the World Health Organization (WHO) in February 2018 on their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic.

Portage Biotech aims to expand the number of patients benefiting from immunotherapies. They are developing precision immuno-oncology therapies like natural killer T cell engagers and adenosine inhibitors. The CEO, Dr. Ian Walters, shares their unique approach to targeting resistant pathways. Portage Biotech is focused on collaborations and conducting randomized studies to show the efficacy of their drugs. The speakers also discuss challenges in clinical trials and the impact of COVID-19.

This week’s podcast is sponsored by Vetter.On this week’s episode, we have a conversation with Steve Worland, CEO of eFFECTOR Therapeutics.eFFECTOR is a clinical-stage biopharmaceutical company pioneering the development of a new class of oncology drugs referred to as STRIs (selective translation regulation inhibitors). eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interacting kinase (MNK). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. The company’s product candidates are designed to act on a single protein that drives the expression of a network of functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. The lead product candidate, tomivosertib, is an MNK inhibitor currently being evaluated in KICKSTART, a randomized, double-blind, placebo-controlled phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC). Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently being evaluated in phase 2a expansion cohorts in certain biomarker-positive solid tumors, including ER+ breast cancer and KRAS-mutant NSCLC. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E.

Cue Biopharma is researching cytokine-based drugs to activate T cells against tumors. Their approach delivers cytokines specifically to cancer cells for targeted treatment. The podcast discusses the advantages of cytokine-based drugs in cancer treatment, including shorter treatment time and increased overall survival. They highlight promising results in activating the immune system and mention the potential of cell therapies.

On this week’s podcast, to recognize Blood Cancer Awareness Month, we have a conversation with Affimed's CMO, Andreas Harstrick, to talk about blood cancers, and what Affimed is doing to tackle blood cancers.One of the main challenges in treating blood cancers is the limited options for therapeutic intervention. Treatment relies primarily on chemotherapy, which is often associated with high toxicity and limited duration of response. Most other approaches to treating hematologic tumors target the adaptive immune system, neglecting the importance of innate immunity. However, harnessing the body’s first line of response could be an important gateway to treating these cancers, which could drastically lower side effects and overcome immune evasion by cancers, especially in refractory or relapsed patients. Approaches based on the innate immune system mainly utilize NK (natural killer) cells. Innate Pharma, Dragonfly Therapeutics, and Affimed are among the biotech companies directing NK cells to tumors with the help of bi- or multi-specific antibodies. Affimed has completed a phase 2 trial with its innate cell engager (ICE), AFM13. To address the fact that cancer patients often lack a functional immune system, Affimed has combined its ICE approach with PD-1 inhibitors or allogeneic cord blood-derived NK cells to further increase the potential success of its treatments. Initial results from an exploratory study together with MD Anderson have already provided encouraging data with relapsed or refractory patients that previously exhausted all treatment options showing a complete response rate of 71% when treated with AFM13 precomplexed with cord blood-derived NK cells.

On this week’s podcast, we have a conversation with Dr Jack Scannell, CEO of Etheros Pharmaceuticals Corp. Scannell recently co-authored a paper on the expenses related to clinical research and the factors that underly the translational failure of inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) in oncology.Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors, published in Jama Network Open, looked at 16 inhibitors of IGF-1R, in 183 clinical trials involving more than 12,000 patients. None of the agents received approval for clinical use in oncology practice and the trials were estimated to have had expenses of greater than $1.6 billion. Half of the published in vivo preclinical data analyzed showed less than a 50% inhibition of tumor growth by IGF-1R inhibitors.The authors stated that failed drug development in oncology incurs substantial expense. At an industry level, an estimated $50 billion to $60 billion is spent annually on failed oncology trials. Improved target validation and more appropriate preclinical models are required to reduce attrition, with more attention paid to decision-making before launching clinical trials. A more appropriate use of resources may better reduce cancer mortality, the authors argued.

Since its inception in 2012, World Lung Cancer Day has been observed every year on August 1 in order to raise awareness of lung cancer issues and magnify the need for more lung cancer research funding.Around a quarter of a million people in the US alone will be diagnosed with some form of lung cancer in 2023. And more than 125,000 people in the US will die from the disease. And another pretty awful stat is that one in 16 men and one in 17 women will be diagnosed with lung cancer, which kills three times as many people as breast cancer or prostate cancer. However, there are some positive trends. The number of new lung cancer diagnoses is declining steadily. Since 2006, the incidence rate decreased by 2.6% per year in men and 1.1% per year in women. Mortality rates are declining even faster, because of advances in treatment and early detection.This week’s guest is Prof. Iris Barshack, Head of the Pathology Institute at Sheba Medical Center, to talk about a new diagnostic tool for lung cancer.Sheba Medical Center’s new AI cancer diagnostics platform reduces diagnosis timeSheba Medical Center, Israel’s largest medical center, has announced the deployment of a new accelerated, AI-powered cancer diagnostics research platform to improve patient diagnosis,  treatment and outcomes. The platform enables the integration of AI technology developed by Sheba in addition to solutions created by innovative digital health startups.One of the first AI solutions to be deployed was developed by Imagene, an emerging leader in AI-based precision oncology, incorporating an algorithm to identify actionable biomarkers of non-small cell lung cancer. The algorithm is directly applied to a digitized image of a conventionally stained pathology slide and can then, within minutes, identify the presence of actionable biomarkers in the tumor, thus providing crucial information for diagnostic and therapeutic decisions. The solution essentially shortens diagnostic time from three weeks to minutes, enabling patients to begin treatment earlier. “We have reached another significant milestone in digital pathology with this ability to detect biomarkers by AI. The use of deep learning algorithms is changing the world of diagnosis, and in certain cases can drastically shorten the cost and time to treatment. I am excited to hear about the growing number of patients who were able to receive rapid diagnoses and treatment using our new service,” said Prof. Iris Barshack, Head of the Pathology Institute at Sheba Medical Center.This latest advancement in cancer diagnostics builds on the progress Sheba’s Pathology Institute has made in recent years. In 2019, the pathology lab at the hospital went fully digital, using computer screens for diagnosis instead of microscopes. Once the lab turned fully digital, the team worked with Imagene who developed a rapid AI-based molecular profiling algorithm to identify actionable biomarkers from the digital biopsy image alone.        “We are very proud to be part of this incredibly important initiative by Prof. Barshack to facilitate an accelerated program for rapid diagnosis of cancer patients,” said Dean Bitan, co-founder and CEO of Imagene. “It takes an innovative approach and openness to new and advanced technologies to drive cancer research and advanced cancer care. We believe this program will showcase the importance of rapid molecular profiling within the clinical workflow.” To dive deeper into the topic: Seven lung cancer companies advancing new treatments in 2025The future of NSCLC treatment: what’s in store for the therapeutic space?