Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Chris Spivey

Behind the Headlines: Weight Loss Drugs; Price Controls; and Free COVID Therapies

This Behind the Headlines news roundup panel discussion covers news items such as the weight loss drugs battle between Novo Nordisk and Eli Lilly, entering new territory through Lilly’s partnership with HAYA Therapeutics and long non-coding sequence mining. It was questioned whether HAYA would have turned its platform toward obesity without that market commanding so much commercial attention at present.

“The partners will identify multiple regulatory genome derived RNA-based drug targets to address these chronic conditions. Under the terms of the collaboration, HAYA will receive an upfront payment, including an equity investment, and is eligible to receive up to an aggregate $1 billion in pre-clinical, clinical and commercial milestone payments, as well as royalties on product sales. HAYA’s proprietary regulatory genome discovery platform enables the identification of tissue-, disease- and cell-specific long non-coding RNA (lncRNA) targets and the development of RNA-targeting therapies, with potentially better efficacy and less toxicity than current treatments, to reprogram disease-driving cell states … This partnership with Lilly demonstrates the significant advances we have made with our revolutionary regulatory genome RNA-guided platform and validates the potential of targeting lncRNA for chronic conditions," said Samir Ounzain, CEO, HAYA Therapeutics, in a press release (1). "We look forward to working closely with Lilly, an established leader in developing treatments for metabolic diseases, to help bring patients novel disease-modifying therapeutics that could offer greater efficacy, safety and accessibility than currently available treatments” (1). 

The panel also discussed The Centers for Disease Control’s Director Many Cohen’s decision to make free vaccines available for those who otherwise couldn’t afford them ($62 M). Starting in late September 2024 from the 

 website, each household can order up to four free at-home tests, which will be delivered through the mail. This is a popular program that has sent out more than 900 million tests since 2021, according to Dawn O’Connell, Health and Human Services’ assistant secretary for planning and response. O’Connell said the government’s Paxcess program, which is run by drugmaker Pfizer, will continue to distribute free Paxlovid through the end of the year to people who test positive for COVID-19 and who are uninsured or who are on Medicare or Medicaid (2).

An advance in mitochondrial basic biological understanding with ramifications for potential disease etiology and diagnostics, alongside drug targeting was also discussed. A recycling system in self-repairing mitochondria has been reported by imaging scientists at the hospital for sick children (SickKids). A report by 

 stated, “their research demonstrates mitochondria can recycle a localized injury, removing damaged folds called cristae that contain proteins and molecules needed for energy production. The researchers believe this mechanism could present a future target for the diagnosis and treatment of conditions characterized by mitochondrial dysfunction, including infections, fatty liver disease, aging, neurodegenerative conditions, and cancer” (3).

The panel also discussed the Biosecure Act passage and re-shoring pharma manufacturing to North America. In a survey of small, emerging biotech firms in the United States, the Biotechnology Innovation Organization (BIO) found that 65% work with China-based contract development and manufacturing organizations in some capacity. Switching to new manufacturers, or manufacturing in the US, would temporarily halt production and potentially cost more in labor (4).

HAYA Therapeutics. HAYA Therapeutics Announces Collaboration with Lilly to Discover Novel Regulatory Genome Targets for Obesity and Related Metabolic Conditions Using Proprietary RNA Platform. Press Release. Sept. 4, 2024. 

https://www.hayatx.com/news-and-publications/haya-therapeutics-announces-collaboration-with-lilly

Goodman, B. Free Covid Tests, Treatments Will Return to Help the Country Cope Over Fall and Winter, US Officials Announce. 

https://www.cnn.com/2024/08/23/health/free-covid-tests-treatments-2024/index.html

Genetic Engineering & Biotechnology News. Recycling System in Self-Repairing Mitochondria Discovered. 

https://www.genengnews.com/topics/translational-medicine/recycling-system-in-self-repairing-mitochondria-discovered/

Vedantam, K. US Manufacturing Unprepared for BIOSECURE Act’s Repercussions. 

https://www.biospace.com/policy/us-manufacturing-unprepared-for-biosecure-acts-repercussions

Alex Philippidis, Senior Business Editor, Genetic Engineering & Biotechnology News

Benjamin McLeod, Director, Cell & Gene Therapy Segment, NanoMosaic Inc.

Chris Spivey, Director of Industry Relations and Strategic Partnership, MJH Life Sciences

Videos

This Behind the Headlines news roundup panel discussion covers news items such as the weight loss drugs battle between Novo Nordisk and Eli Lilly, entering new territory through Lilly’s partnership with HAYA Therapeutics and long non-coding sequence mining. There was much discussion on how the inflation reduction act and Medicare price controls may or may not pertain—given the uncertainty around the presidential election results, and subsequent policy directions. The Centers for Disease Control making cost free COVID-19 diagnostics and therapies available was also evaluated. 

Vernal Biosciences’ CEO and founder, Christian Cobaugh, discusses the outsourcing landscape for mRNA production.

A Discussion on the Outsourcing of mRNA Production (BIO  2024)

At BIO 2024 in San Diego, Calif., which was held on June 3–6, 

 Group’s Chris Spivey spoke with Christian Cobaugh, PhD, Vernal Biosciences’ CEO and founder, about the outsourcing landscape for messenger RNA (mRNA) production. Vernal’s simplified business model for manufacturing all stages of mRNA R&D galvanized the company into contributing comments to FDA’s 

Guidance on Platform Technology Designation Program for Drug Development

 (1), in which—once consistent with the statutory conditions required to be compliant with chemistry, manufacturing, and controls (CMC) processes—applicants can re-use certain foundational modules without having to go backwards and prove that module repeatedly. Cobaugh, along with Vernal’s senior director of commercial and technical operations, Grant Henderson, PhD, and guest contributor, Khaled Yamout, analytical sciences, quality, and manufacturing consultant at Y-Chem Consulting, shared their thoughts in an Aug. 1, 2024 blog article (2). 

Christian Cobaugh, PhD, CEO & Founder, Vernal Biosciences. Image courtesy of Vernal Biosciences.

Looking at the field of mRNA service providers Cobaugh divides the landscape into two categories. “There [are] those that just generally do GMP [good manufacturing practice] for multi different types of drug products. and then there [are] more specialty companies that were set up to make nucleic acids. In our position [in] mRNA, we have several years of trial runs on the manufacturing technology platform, performing research-grade processing before we flipped over into GMP,” he said in the BIO interview with Spivey.

While innovation on specific steps were needed, one of the areas requiring the most improvements were the analytics, Cobaugh said, noting that “there's a lot of complexity there. Part of manufacturing is controlling what you're manufacturing, and, in order to do that, you've got to have unimpeachable analytical and QC [quality control] capabilities. And so that was something that kept me up at night, [but] no longer does. The number of platforms that we've got to use for release testing is quite daunting. and we've mastered pretty much all of them.”

Among the most promising of the new higher performing analytical approaches is next-generation sequencing (NGS). Cobaugh pointed out that “NGS offers … an opportunity to go deeper and pick off multiple critical quality attributes from the same test, which, along with consolidating platforms more broadly, presents significant cost of goods savings in the long run.”

Located in Vermont, Vernal has been manufacturing mRNA and lipid nanoparticle (LNP) products for clients since 2021. The company offers custom mRNA, mRNA sequence design, GMP mRNA and LNP–mRNA manufacturing, and LNP-formulated mRNA products. Vernal takes a stage-gated approach to offer GMP mRNA and LNP production services and recently upgraded its manufacturing space, QC lab, warehouse, and additional lab and office space in a total building area of 23,000 square feet. The company is also planning a new 20,000 square-foot GMP mRNA manufacturing plant, which it expects to bring on line in the near future.

Draft Guidance for Industry, Platform Technology Designation Program for Drug Development

 (CDER, CBER, May 2024).
2. Cobaugh, C.; Hendersonm G.; Yamout, K. FDA Guidance on Platform Technology Designation Program for Drug Development. 

vernal.bio/news-insights/blog-fda-guidance-on-platform-technologies

Behind the Headlines: Mpox Resurges; Eli Lilly Adds CGT Facilities; FDA Updates

This Behind the Headlines news roundup panel discussion covers news items such as the resurgence of mpox in Africa, “medical tourism” in India, Eli Lilly’s new Boston CGT facilities, and contract development and manufacturing organization (CDMO) projected growth rates for the 2023–2029 period, and the reasons behind them.

The panel also discussed at more length the surge, or more appropriately the revitalization of interest, in the antibody-drug conjugate (ADC) space. In August 2024, Merck said it will pay an initial $700 million to acquire full global rights to clinical-stage bispecific antibody CN201 from privately held biotechnology company Curon Biopharmaceutical. Why was there so much excitement about ADCs at the recent BIO Conference in San Diego

The panel also talked about FDA leadership, especially in regard to training how to solve common problems but also in how best to train staff generally. A 

 notice dated Aug. 8, 2024 announced FDA’s Fiscal Year 2025 for the Center for Drug Evaluation and Research (CDER) Office of Pharmaceutical Quality (OPQ) Experiential Learning Site Visit Program (ELSVP) (1). As per their press release, the ELSVP, “allows staff to observe commercial manufacturing and testing operations as well as pilot plants, with the goal of better understanding standard operations of the pharmaceutical industry and how those impact the developmental programs and commercial life cycles of drugs. It does not replace or supplement a regulatory inspection” (1).

Also, due to the rapid expansion of cell and gene therapies (CGT), FDA has launched the Cellular and Gene Therapies Interactive Site Tours Program. “This initiative allows FDA staff to visit industry sites, facilitating an exchange of regulatory and industry best practices. By gaining first-hand insight into the manufacturing process, the FDA aims to enhance its review capabilities and foster a deeper understanding of biotech operations. This collaboration between industry and the regulatory body is a crucial step towards streamlining the development of ATMPs [advanced therapy medicinal products], ultimately benefiting patients and advancing the field of biotechnology” (2).

As a final wrap-up, the panel looked at the idea that the dark days of 2023 investment are now squarely behind us, and that the dawn of stronger investment sentiment is coinciding with a broader adoption cycle of artificial intelligence and machine learning equipment and innovation. This presages well for a boom two-year cycle, which is about to provide unusually high levels of industry growth opportunities for nearly all stakeholders—ultimately passing on rewards to most patient populations, and especially those in the rare disease category.

Lavery, P. Drug Companies Encouraged by FDA to Participate in FY 2025 Site Visitation Program. 

https://www.pharmtech.com/view/drug-companies-encouraged-fda-participate-fy-2025-site-visitation-program

Manalac, T. FDA Eyes Site Tours of Cell and Gene Therapy Manufacturers. 

Dr. Laks Pernenkil Principal, US Life Sciences Product, Supply and Manufacturing Operations Practice Leader, Deloitte Consulting

Beth Willers, Principal and Owner, White Matter Communications

This Behind the Headlines news roundup panel discussion covers news items such as the resurgence of mpox in Africa, “medical tourism” in India, Eli Lilly’s new Boston CGT facilities, and contract development and manufacturing organization (CDMO) projected growth rates for the 2023–2029 period, and the reasons behind them. 

Nadia Sellami, PhD, global segment lead for gene and cell therapy at PacBio interview

The Benefit of Long-Read Sequencing in Gene Therapies

At the American Society of Gene and Cell Therapy (ASGCT) conference in Baltimore, Md. in May 2024, 

® sat down with Nadia Sellami, PhD, global segment lead for gene and cell therapy at PacBio, about the benefits of long-read sequencing in cell and gene editing.

According to Sellami, long-read sequencing detects information that short-read sequencing cannot capture. “And in contrast to other long-read sequencing methods, it has higher accuracy while maintaining the same read length,” she says in this video interview. “So, for example, you can see long indels that you might get from gene editing. You can sequence the entire AAV [adeno-associated virus] molecule, ITR [inverted terminal repeat sequence] to ITR. You can sequence plasmids. You can sequence full length mRNA [messenger RNA] and so many more sequencing applications.”

DNA sequencing is important for the design, production, and quality of gene therapies, says Sellami. Click the video box above to view the full interview.

For more coverage from the 2024 ASGCT conference, visit PharmTech.com’s 

Highlighting Personalized mRNA-Based Vaccines for Pancreatic Cancer

Research Shows that HIC Can Effectively Separate Deaminated Capsids from Non-Deaminated Capsids

Using Receptor Architecture to Improve CAR-T Cell Sensitivity in Oncology

The Role of Bispecific Antibodies in Redirecting AAV Vectors

Nadia Sellami, PhD, global segment lead for gene and cell therapy at PacBio, talks about long-read sequencing for cell and gene editing in a video interview. 

Mary (Nora) Disis, MD, University of Washington

Pablo Guasp, PhD, Memorial Sloan Kettering Cancer Center (MSK)

American Society of Gene and Cell Therapy’s (ASGCT’s) 27th Annual Meeting

 in Baltimore, Md., which occurred May 7–11, 2024, Pablo Guasp, PhD, MSK asked himself the question, “What can we use to teach the immune system how to recognize cancer cells?” Replying, “… the neoantigen that arise from the accumulation of mutations in cancer cells can be good candidates … while a limitation is that neoantigens usually impose a restriction towards personalized treatments; therefore, we need a delivery platform that allows for modularity where we can include and exclude neoantigens based on the mutations of each individual patient. Also, we need a platform that allows us to do this in a timely manner, so we can treat patients soon after they are diagnosed. We believe that nucleic acid [developments] have been a breakthrough in this field, and in particular mRNA [messenger RNA] is showing very promising results”. Guasp then considered which patients benefit the most from this approach, stating, “If we look at vaccines against infectious agents we see that vaccines are always given in a prophylactic setting before the patient develop[s] the disease. But, paradoxically, cancer vaccines historically have been tested in patients with advanced and metastatic disease, and we think that this may not be the best scenario. We think that cancer vaccines may work best in patient with minimal disease, such as patients that had their tumors surgically resected” he averred. 

MSK partnered with BioNTech and Genentech to launch the first clinical trial of personalized mRNA cancer vaccines in pancreatic cancer. The results of this trial were published in 2023 (1). In only nine weeks, patients were receiving their own individualized cancer vaccine. This happened in such a timely manner, “because of a huge collaborative effort between all the members involved in the teams, but also because mRNA allows for this quick modularity, and this speed that I was mentioning before,” Guasp said.

During those nine weeks, the patient received a single dose of anti programmed cell death ligand 1 immunotherapy with atezolizumab and then received eight priming doses of the vaccine, followed by a standard-of-care chemotherapy and a single vaccine boost dose. “We identified specific responses elicited by the vaccine in half of the patients that receive[d] the vaccine. Not only that, but response to the vaccine correlate[s] with a delay recurrence time. … We know that this is a small clinical trial with a small number of patients, but the results are promising” Guasp added.

1. Rojas, L. A.; Sethna, Z.; Soares, K. C.; et al. Personalized RNA Neoantigen Vaccines Stimulate T Cells in Pancreatic Cancer. 

, 144–150. DOI: 10.1038/s41586-023-06063-y

Articles

In an ASGCT Panel on nucleic acid- and cell-based vaccines in oncology, work on a personalized mRNA vaccine was highlighted.

Highlighting Personalized mRNA-Based Vaccines for Pancreatic Cancer (ASGCT 2024)

In this video, Chris Spivey, Director, Industry Relations and Strategic Partnerships, talks with industry experts about aspects of drug product stability.

Drug Digest: Is Our Understanding of Stability Changing

In this exclusive Drug Digest video interview, Chris Spivey, Director, Industry Relations and Strategic Partnerships, interviews Nitin Swarnaker, Pharma Applications Manager, BASF, and Geoff Carr, Former Director, Analytical Development, Thermo Fisher Scientific/Patheonabout various aspects of drug product stability testing. Stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. Over the last decade there has been some intermixing of supply chain storage and distribution systems, and traditional formulations taking these storage and delivery systems into account—continuous monitoring comes to mind. While long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH. Accelerated Predictive Stability (APS) studies, carried out over a 3–4-week period and combining extreme temperatures and RH conditions (40–90 °C)/10–90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner.

Nitin is a Formulation scientist with over 16 years of combined (academic research/training/industrial) experience, and a very strong track record of publications, primarily focused on various formulation aspects of small, peptide and protein molecules for oral and parenteral applications. He has vast experienced in solid, solution, suspension, semisolid products and novel drug delivery systems such as lipid- and polymer-based drug delivery systems (proliposomes and liposomes, liquid crystalline particles nanoparticles and microspheres) including their targeted drug delivery counterparts. He is well-versed in various characterization techniques used in formulation development, possesses a good understanding of various regulatory guidelines and cutting edge concepts and technologies.

Former Director, Analytical Development, Thermo Fisher Scientific/Patheon

Geoff Carr, PhD, has retired after over 45 years experience of working in the pharmaceutical industry and currently provides training and consultancy services to pharmaceutical companies with an emphasis on the application of good chemistry in the development of new pharmaceutical products. Previously, he was appointed as Manager, Analytical Development at Patheon Inc, Canada in 2000 and progressed to Director, Analytical Development, Thermofisher Scientific/Patheon until 2023. Prior to that, he held positions of Manager, Analytical Sciences at Celltech-Chiroscience, UK, Head of Analytical Development at Medgenix, Belgium and before that at Wyeth Research, UK. He originally started his career in pharmaceutical analysis at The British Pharmacopoeia Laboratory where he held several posts and was finally appointed Head of the Laboratory. His academic background is a PhD in synthetic organic chemistry awarded by University of London, UK. He has been a member of various British Pharmacopoeia Committees, a UK representative to Committees of the European Pharmacopoeia and Member of USP Committees including a Member of the 2015-2020 Cycle USP General Chapters – Physical Methods Expert Committee. He is the author of numerous publications including journal articles and book chapters as well as presentations and workshops at international conferences on various topics related to applications of analytical chemistry during the development of pharmaceutical products. This includes a 8 module distance learning course on Pharmaceutical Stability Testing.

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

® editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

 Biologic Drug Development and Manufacturing

In this exclusive Drug Digest video interview, Chris Spivey, Director, Industry Relations and Strategic Partnerships, talks with industry experts about various aspects of drug product stability testing.