This week on The Genetics Podcast, Patrick is joined by Kent Rogers, Chief Executive Officer at EveryONE Medicines. They discuss Kent’s journey across every side of the desk in the drug discovery space, EveryONE Medicines’ efforts to develop antisense oligonucleotides for ultra-rare diseases, and the need to adapt regulatory models for n-of-1 therapies.

Show Notes: 

00:00 Intro to The Genetics Podcast

00:59 Welcome to Kent and his experiences across every side of the pharma ‘desk’

06:00 Challenges of commercialization for ultra-rare disease therapies and the advantage of antisense oligonucleotides (ASOs) 

10:28 EveryONE Medicines’ approach to regulatory bodies

12:30 Regulatory feedback and expectations from EveryONE Medicines’ platform-based approach to n-of-1 therapies

15:47 Differences in regulatory requirements for rare disease across countries 

19:53 Insights from being on different sides of the drug development industry

22:40 Differences in healthcare systems across countries that can facilitate or impede drug development

26:57 Rationale behind focusing on ASOs for treating rare diseases

28:03 Building EveryONE Medicines and Kent’s approach to leadership

33:20 Lessons from Kent’s career

37:17 Closing remarks 

Find out more

• EveryONE Medicines (https://www.eomeds.com/)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Matt Burgess, genetic counselor, host of the Demystifying Genetics podcast, and Adjunct Professor at Bay Path University. They discuss the evolution of genetic counseling, ethical challenges in gene therapy, and Matt’s experiences with his podcast.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Matt

02:09 Matt’s run-ins with Olivia Newton John while working at Austin Hospital in Melbourne

04:34 Matt’s background and path to genetic counseling 

06:58 The evolution of the field of genetic counseling over time and the role of counselors

12:47 Matt’s work on rare disease AP-4 hereditary spastic paraplegia (AP-4-HSP) and the ethical considerations of gene therapy

20:22 Balancing the needs and expectations of individuals and families in counseling 

23:06 Rebranding negative connotations of the word “counseling” 

26:58 Memorable episodes from Matt’s podcast Demystifying Genetics

34:31 Differences in genetic counseling and healthcare in the US versus Australia and the UK

40:00 Matt’s current work on writing a novel, starting a company called Rosalind Genetics, and being involved in genetic education

42:47 The potential and drawbacks of AI models in the context of genetic counseling and information

46:46 Closing remarks

Find out more

• Demystifying Genetics (https://demystifying-genetics.buzzsprout.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Salvador Rico, Chief Medical Officer at Encoded Therapeutics. They discuss Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and fundamental challenges and exciting advances in the genetics field.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Salvador and how he became involved in drug development

11:01 Frustrations and rewards of the genetics field

13:59 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)

19:46 Risk of liver issues in gene therapy trials and attempts to mitigate them

24:22 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team

27:22 Steps towards therapeutic targeting of gene regulatory elements 

30:04 Advantages of different methods for drug delivery 

32:31 DNA- versus RNA-based therapy

34:56 Insights from approaches in other fields, including psychiatry

36:35 Considerations for using natural history studies

40:32 Expectations and goals for Encoded Therapeutics’ current and upcoming studies

43:17 Closing remarks

Find out more

• Encoded Therapeutics (https://encoded.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Leeland Ekstrom, CEO and co-founder of Nashville Bio. They discuss how Leeland went from being a consultant on a project for Vanderbilt University to a co-founder of a start-up and the unique aspects of NashBio’s clinical and genetic database.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Leeland and the origin story of Nashville Bio

05:13 Process of setting up NashBio’s genome resource with 250K individuals

11:52 How different pharmaceutical companies responded to NashBio’s database and its unique advantages compared to others

17:50 Key priorities for applications of the resource beyond target discovery

20:19 The process of selecting additional gaps that NashBio’s services can fill versus letting others fill them

25:02 Advantages at Vanderbilt Medical Center that facilitated the project and how it can be replicated at other centers

30:32 Immediate and long-term impacts of current NIH funding cuts on biotech and academia

36:43 NashBio’s current major focuses and future goals

39:20 Closing remarks

Find out more

• NashBio (https://nashbio.com/)

• Press release: Alliance for Genomic Discovery completes 250,000 whole genomes to accelerate drug discovery (https://www.illumina.com/company/news-center/press-releases/press-release-details.html?newsid=b4b0c901-f8a2-4802-a4ef-b81167e24cfe) 

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Sharon Terry, President & CEO of Genetic Alliance. They discuss how Sharon established a layperson-led biobank, her long-term work on rare diseases and patient advocacy, and her program to bring genetic technology to patients in low- to middle-income countries.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Sharon and a discussion of the personal experience with rare disease that started her journey

03:47 Reasons why Sharon decided to establish the first layperson-led biobank

05:34 Challenges with setting up the biobank infrastructure

07:00 Balancing financial factors in a non-profit organization 

09:30 Recent patterns and future insight into rare disease drug discovery framework and regulation

15:32 Barriers to widespread collaboration and cooperation in rare disease research, and why it should be approached from a public health perspective

18:12 Background and experiences from the iHope Genetic Health program in low- to middle-income countries

24:44 Sharon’s perspective on current challenges with the Genetic Information Non-discrimination Act

28:49 Sharon’s lessons learned in her patient advocacy and policy work, and her hopes for future legislation

33:04 Sharon’s hopes for improved access to genetic testing and treatment for children in underserved communities

34:34 How Sharon learned about rare diseases and genetics as a “homeschooling mom without a degree”

37:54 Insights into how elements of spirituality can support advocacy work

40:18 Closing remarks

Find out more

• Genetic Alliance (https://geneticalliance.org/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Dr. John Lepore, physician-scientist and CEO of ProFound Therapeutics. They discuss ProFound Tx’s mission to expand the proteome to identify novel drug targets – which resulted in the ProFoundry atlas – and the ways in which John’s diverse experiences inform his approach as a leader.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to John

02:01 John’s background at GSK and his transition to drug discovery

05:45 Establishing ProFound Therapeutics to expand the proteome and identify novel drug targets 

08:27 Genomic origins of newly-identified proteins and the process of finding them

09:49 Developing the ProFoundry atlas and integrating data across assays 

15:27 Different approaches to inferring protein links and association to disease

17:13 Collaboration with Pfizer to find regulators in the context of obesity

18:04 Developing novel antibody-drug conjugates for cancer treatment

20:27 Clarifying causality in proteomic data

21:59 Approaching novel targets while considering industrial and business factors

25:19 John’s background as a cardiologist and how that impacts his current work

27:26 Tips for biotech companies looking to be noticed by pharma for collaborations

30:30 Considerations for investigating new and different therapeutic modalities and techniques

33:39 How John consistently reinforces the translational angle as a business leader

36:24 Closing remarks and future direction for ProFound Therapeutics

Find out more

• ProFound Therapeutics (https://www.profoundtx.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Raghib Ali, CEO, CMO, and Principal Investigator of Our Future Health UK. As a clinical epidemiologist with a passion for reducing health inequalities, Raghib offers fresh insights into the priorities, challenges, and transformative impact of the groundbreaking genomics initiative, Our Future Health. 

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Raghib and background on Our Future Health (OFH)

03:57 Diseases that are a priority for OFH or are likely to benefit from its impact

06:07 Challenges and opportunities for implementing change in the National Health Service (NHS), a partner of OFH, based on study findings

09:20 Factors that contributed to the rapid recruitment of participants to OFH

14:12 Efforts to ensure diversity of OFH participants and facilitate accessibility for all

16:35 Why OFH chose to use arrays for genomic profiling

18:57 Navigating the obstacles and opportunities in public and private partners

22:28 Strengths and weaknesses of the medical record system in the UK

25:54 Efforts to rapidly provide results from OFH and integrating other datasets and techniques in the future

28:43 Raghib’s unique educational and training journey 

31:49 The importance of evaluating components beyond genetics for a full picture of health

33:28 Aims and findings of the first prospective cohort study in the UAE

35:26 The potential contribution of epigenetic inheritance to disease risk 

37:43 How Raghib overcame adversity early in life

40:56 Closing remarks 

Find out more

• Our Future Health (https://ourfuturehealth.org.uk/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, we’re celebrating Rare Disease Day with a very special episode. Patrick is joined by clinical nephrologist Anthony Bleyer and geneticist Stan Kmoch to discuss how their decade-long international collaboration has uncovered genetic mutations in families with rare inherited kidney diseases – including Patrick’s.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Anthony and Stan

02:05 The origin story for Anthony and Stan’s long-distance collaboration

06:55 Stan’s background in metabolic disorders and sequencing techniques

11:09 Common genetic culprits and barriers to identifying mutations that cause kidney disease

14:01 Background and findings from Anthony and Stan’s ApoA4 study

23:54 Potential therapeutic avenues based on the ApoA4 study

26:49 Current and future focuses for characterizing diseases in families

30:42 Working with collaborators internationally to access large databases and registries

33:05 Innovative transplant methods, including genetically-modified pig kidneys

36:36 Closing remarks and a heartfelt thank you to researchers and families driving rare disease research

Find out more

• Latest study: https://doi.org/10.1016/j.kint.2023.11.021

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Michelle Werner, CEO at Alltrna and CEO/Partner at Flagship Pioneering. They discuss Alltrna’s promising findings from its first preclinical study on using tRNA to rescue stop codon disease, the strategic use of basket trials, and more!

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Michelle

02:13 Overview of Alltrna’s aims and the advantages of using tRNA to tackle stop codon disease

5:27 Using basket trials for genetic diseases

08:03 Highlights from Alltrna’s first preclinical study using tRNA to restore protein production to clinically meaningful levels in methylmalonic acidemia (MMA) and phenylketonuria (PKU)

14:02 Considerations in delivery techniques and Alltrna’s use of nanoparticles

19:22 Stability of tRNA and how engineered tRNAs are recognized in vivo 

23:12 Strategic design of basket trials and diseases that are covered

26:16 Adaptive trial design in the rare genetic disease setting

28:15 Michelle’s experience with regulatory organizations on new approaches to trial design

32:14 Insights from spearheading Alltrna and Flagship Pioneering’s innovative approaches 

37:26 Michelle’s lessons from working in big pharma versus a small biotech start-up

40:50 Closing remarks and a call for collaborators

Find out more

• Alltrna (https://www.alltrna.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

On this week’s episode of The Genetics Podcast, we’re joined by Jocelynn Pearl, Director of Cancer Cell Therapy at the TAM Center, host of the Lady Scientist Podcast and Co-Founder of LabDAO. Patrick and Jocelynn discuss her move to Mexico to help accelerate the development of new cancer therapies, harnessing the power and potential of decentralized science, and overcoming sky-high gene therapy costs to increase accessibility for patients.

Show Notes: 

0:00Intro to The Genetics Podcast

01:00Welcome to Jocelynn

02:03 Jocelynn’s past work at The Institute for Systems Biology 

04:55 How Jocelynn approached her transition to biotech from the world of academia

10:14 Exploring decentralized science, including how it works and Jocelynn’s involvement to date

15:54 What a Decentralized Autonomous Organisation (DAO) is and how this type of organizational structure supports scientific development

22:45 The “fast grant” surge and other non-traditional funding methods

28:00 Hosting the Lady Scientist Podcast and some of Jocelynn’s favorite moments

32:43 Jocelynn’s move to Mexico to serve as Director of Cancer Cell Therapy at the TAM Center

36:12 The biggest differences between building out drug development programs in Mexico and the US

38:31 Regulatory differences between countries in the context of stem cell therapies

42:48 The advantages for cancer therapeutic development in Jocelynn’s current environment

46:20Driving down the costs of gene therapies and the impact on accessibility  

48:09 Closing remarks

Find out more

LabDAO:https://www.lab.bio/ 

Please considerrating and reviewing us on your chosen podcast listening platform!https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj 

Summary: 

This week on The Genetics Podcast, Patrick is joined by Eric Adler, Chief Medical Officer and Head of Research at Lexeo Therapeutics and Professor of Medicine at University of California San Diego. Eric shares his experience with genetic cardiomyopathy and his work on gene therapy for Danon disease, drawing from both clinical and research perspectives. Additionally, he explores the evolution of the field and the broader challenges faced by cardiovascular patients.

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Eric and his efforts in cardiomyopathy at the bench and bedside

03:32 How modeling genetic diseases using pluripotent stem cells lead Eric to studying Danon disease 

04:50 Pivoting from basic to translational research using adeno-associated viruses (AAV)-based gene therapy

07:58 Uncovering genetic cardiomyopathies that were misdiagnosed as idiopathic cardiomyopathy

09:55 Treatment, screening, and penetrance of Danon disease

12:30 Recent successes and remaining challenges in cardiovascular disease

19:47 Battling distrust in the medical profession

21:55 Preventative therapy using APOE2 for patients at risk of early Alzheimer’s

25:15 Motivations behind and advantages of Eric’s patient-centered approach to therapeutics

27:24 Balancing regulatory requirements for protocols versus patient needs

29:49 The importance of committed clinical partners for successful trial execution

36:08 Eric’s passion for cooking and how he won a cooking competition

39:02 Closing remarks and Lexeo Therapeutics’ aims for 2025

Find out more

• Lexeo Therapeutics (https://www.lexeotx.com/)

Please consider rating and reviewing us on your chosen podcast listening platform! 

https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link