Dose of Discovery

It may seem obvious, but not all drugs are manufacturable. Getting an exciting new treatment from the lab to patients is only possible if the molecule or substance itself is scalable. In this episode of Dose of Discovery, hosts Søren and AJ speak to Cheng Yi Chen, chief technology officer at Asymchem, about the chemistry, scaling up, and decision making behind moving a drug from clinical trials to commercial supply.Cheng Yi shares the story of cancer drug adagrasib and the urgent supply challenge he faced at Mirati Therapeutics, when the original process couldn’t generate enough of the drug to support clinical trials.Their conversation then turns to the broader world of process chemistry: how process routes are designed, the regulatory pathways they must follow, and sustainability issues they face.They also discuss flow chemistry, continuous manufacturing, and why CDMOs play such an important role in helping new medicines reach patients – especially when it comes to dealing with regulators.In this episode:03:48 – Explainer: What are CDMOs?06:50 – Introducing Cheng Yi Chen07:09 – The adagrasib supply challenge at Mirati11:19 – How process chemistry enables clinical progress16:57 – Moving between big pharma, biotech, and CDMOs work27:06 – Peptides, oligos, and the rise of TIDES manufacturing30:44 – Green chemistry, solvents, and cost-effective production36:56 – Flow chemistry and continuous manufacturing44:50 – Creating a manufacturing story for regulators39:48 – China’s growing role in biotech innovation47:57 – Wrap-up and key takeawaysAbout the guestCheng Yi Chen is the chief technology officer at Asymchem. He has held senior process chemistry and drug development roles across Merck, Janssen, Mirati Therapeutics, and Bristol Myers Squibb. His work focuses on developing and manufacturing drug substances and products at scale.Dose of Discovery is cohosted by Søren Hough and Ayokunmi Ajetunmobi (AJ) and produced by Suze Cooper.LINKS:GLP-1s forced industry’s hand on sustainable peptide synthesis, says expert by Søren Hough (Interview with Fernando Albericio) Enzymes open the door for simpler, more efficient oligo therapeutic synthesis by Søren HoughAdaptable manufacturing platforms enable in vivo mRNA-LNP delivery by Søren HoughIndustry pioneers solve the ‘three-body problem’ of RNA synthesis by Søren HoughEli Lilly’s Michael Kopach says retatrutide leads in obesity treatment and CMC innovation by Søren HoughRead more at Bioxconomy, sign up to our newsletter, and don’t forget to check out our upcoming events.You can find a fully annotated transcript of the episode here.

In this episode of Dose of Discovery, hosts Søren and AJ speak to physician-scientist Stanley Crooke, CEO of the nonprofit n-Lorem Foundation, about how antisense oligonucleotide (ASO) technology has evolved into a revolutionary therapeutic modality.Their conversation explores Stan's expansive career journey, from his early days building cancer programs at Bristol Labs and SmithKline to his bold decision to launch Ionis in 1989 when the industry doubted ASO technology.Stan discusses the emotional rollercoaster of biotech drug development, the inefficiencies of traditional small molecule discovery, and what led him to establish the n-Lorem Foundation.He shares how the regulatory frontiers of treating nano-rare genetic conditions “for free, for life” are changing rapidly and why innovations like patient-derived stem cells are driving drug development forward, one patient at a time.In this episode:03:41 – Explainer: What are ASOs?06:50 – Stanley Crooke’s journey and his journey into biomedicine10:31 – Frustrations with big pharma, founding Ionis15:05 – Trailblazing on ASO medicinal chemistry19:33 – Building company culture amid clinical failure22:56 – Spinraza (nusinersen) and the economics of drug pricing28:08 – Launching the n-Lorem Foundation for nano-rare diseases30:57 – “Free for life” ASO therapies36:55 – Impact on n-Lorem’s patients39:36 – “Everything we thought we knew about developmental delay is wrong.”34:58 – Redefining traditional diseases n-of-1 trial success26:12 – “Just tell me what the cause is. I'll fix it.”37:22 – 90% success rate for n-of-1 work45:08 – Moving beyond animal models with patient-derived iPSCs52:23 – Biology is shifting industry toward platforms55:55 – Wrap up and key takeawaysAbout the guestPhysician-scientist Stanley Crooke, founder of Ionis Pharmaceuticals, and founder, chairman, and CEO of the n-Lorem Foundation. Widely regarded as a pioneer of antisense medicine, he helped lead the development and commercialization of the first approved ASO therapies. Today, his work through nonprofit organization the n-Lorem Foundation focuses on creating and providing bespoke ASO treatments to patients suffering from nano-rare genetic conditions (affecting fewer than 30 people worldwide) for free, for life. Crooke studied pharmacy at Butler University and went on to earn his MD and PhD at Baylor College of Medicine.https://www.nlorem.org/wp-content/uploads/2023/08/Stanley-T.-Crooke-M.D.-Ph.D.-Bio.pdfDose of Discovery is cohosted by Søren Hough and Ayokunmi Ajetunmobi (AJ) and produced by Suze Cooper.LINKS:Kinds of KANDness: Battling nano-rare disease with oligos by Søren HoughTherapeutic oligos for no profit: A discussion with n-Lorem by Søren Hough‘For free, for life’: n-Lorem carves path for bespoke treatment by Søren HoughDeep brain penetration by oligos enables Alzheimer’s, Parkinson’s treatment by Søren Hough (ASO treatment for neurodegeneration)Oligo-based therapies lead charge against prion disease by Nnenna Ohaka (Getting ASOs into the brain)Phosphorothioate antisense oligonucleotide induced innate immune activation is attenuated by tryptophan oxidation products (Making safe ASOs by Crooke and colleagues)Establishing a commercial solution for extremely rare genetic diseases (Commercializing ASOs for rare disease by Crooke & Lo)Read more at Bioxconomy, sign up to our newsletter, and don’t forget to check out our upcoming events.You can find a fully annotated transcript of the episode here.

Welcome to Dose of Discovery: a dose of breakthrough medical discoveries, delivered with your morning coffee. (Coffee not included.)In this first episode, hosts AJ and Søren speak to Julia Alterman, assistant professor at the RNA Therapeutics Institute at UMass Chan Medical School, about how siRNA technology has evolved from a useful laboratory research tool into a promising therapeutic modality.Their conversation explores innovations in siRNA chemistry and how these changes have enabled researchers to craft potent siRNA drugs. Julia talks about her unlikely beginnings as a theater major before finding her way into biology – eventually leading her into the biotech industry and academia. Along the way, she discusses the challenges of delivering siRNAs beyond the liver into harder-to-reach tissues such as the brain and muscle, and the serendipitous discovery that helped launch Atalanta Therapeutics.In this episode:04:23 – Explainer: What are siRNAs?08:42 – Meet Julia Alterman12:39 – Julia’s history in industry16:33 – UMass and a PhD pivot18:28 – siRNAs versus ASOs21:39 – siRNAs versus CRISPR28:33 – A serendipitous breakthrough38:02 – Baby steps and big leaps42:10 – Stability and the therapeutic window46:27 – The importance of strong science communication50:55 – Scientists and VC funding54:28 – Wrap up and reflectionsAbout the guestJulia Alterman is an assistant professor at the RNA Therapeutics Institute at UMass Chan Medical School, where she develops new siRNA therapies for genetically defined diseases. Her work spans RNA chemistry, delivery, and pharmacology. Her earlier research into siRNA scaffold was licensed to Atalanta Therapeutics for the treatment of neurodegenerative disease.https://www.umassmed.edu/khvorovalab/People/faculty/Julia-Alterman/Dose of Discovery is cohosted by Søren Hough and Ayokunmi Ajetunmobi (AJ) and produced by Suze Cooper.LINKS:RNA Fact Sheet from the National Human Genome Research InstituteBioXconomy’s coverage of the Alterman and Khvorova labs:"siRNA backbone modifications boost therapeutic potential, study finds" by Nnenna Ohaka (Exploration of exNA)"Cutting-edge siRNA therapy improves ALS symptoms, survival in mice" by Søren Hough (Exploration of divalent siRNAs)"Long-lasting siRNAs could help cancer patients and older people resist muscle loss" by Søren Hough (Including a photo of a Belgian blue cow)"Oligo-based therapies lead charge against prion disease" by Nnenna OhakaRead more at Bioxconomy, sign up to our newsletter, and don’t forget to check out our upcoming events. You can find a fully annotated transcript of the episode here.