Mike Hennessy Jr. is the President and CEO of 

Mike Hennessy Jr.

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Experts believe it is likely cancer cells are more common in the body than previously thought, but typically caught early and removed in the body’s cancer-immune cycle. When the system is in good working order (and protecting us), dead cancer cells release neoantigens, which are acquired by dendritic cells and moved to a nearby draining lymph node for disposal. Dendritic cells then present this antigen to T cells, which become effector T cells, and after a few more steps, “move through the blood toward the tumor tissue. These T cells then infiltrate into the tumor and recognize and bind the MHC-I–antigen complex presented by cancer cells through the T cell receptor. Through these processes, cancer cells are finally killed. …When cancer cells die and additional neoantigens are released, the immune reaction continues the cycle again from the first step. [However], in cancer patients, at least one of these steps is defective and the cancer-immune cycle does not work properly” (1).

The obvious utility in identifying tumor neoantigens is consolidating in weight and importance, leading to coordinated leapfrog advances in pharmaceutical sciences. But each patient has their own personal biology, creating their own personal tumor microenvironment (e.g., there are more than 24,000 distinct human leukocyte antigens) (2). A paper describing a powerful new identification platform was briefly discussed in an interview with 

® (3), where study author, Stephen Schoenberger, told 

 editor “we let the patient’s immune system tell us which mutations can be confirmed as neoantigens and then have asked whether there are bioinformatically quantifiable features of these mutations apparent in genomic sequence data. Our goal in doing so is a computational prioritization algorithm of sufficient predictive power as to obviate the need for 

 functional validation step, as this would be difficult to scale for the number of patients that our findings suggest could benefit from personalized immunotherapy” (3).

Kim, S.; Cho, S. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. 

. 2022 May 24:13:868695. DOI: 10.3389/fphar.2022.868695. eCollection 2022.

Fu, L.; Huang, C.; Huang. Z. Neoantigens: Promising Targets for Cancer Therapy. 

. 2023 8 article 9. Nature.com, https://www.nature.com/articles/s41392-022-01270-x

Spivey, C. Research into Cold Cancers Heating Up. 

When referring to this article, please cite it as Hennessy, M. May I Present the Neoantigen. 

Articles

Experts believe it is likely cancer cells are more common in the body than previously thought, but typically caught early and removed in the body’s cancer-immune cycle. When the system is in good working order (and protecting us), dead cancer cells release neoantigens. 

May I Present the Neoantigen

Novo Holdings’ acquisition of Catalent, in retrospect, was entirely logical (1). We are tempted to see echoes of Thermo Fisher’s buyout of Patheon, or Lonza’s swallowing of capsule maker Capsugel. But this situation is different. Catalent makes significant production of Novo’s Ozempic and Wegovy, but also Lilly’s Mounjaro and Zepbound. And while Catalent’s acquisition is definitely about making drugs, it’s also very much about making money.

Making money takes various forms—taking away a competitor’s capacity to do so is doubtless one of the more intriguing variants. David Ricks, Lilly’s chief executive, was quoted as saying, “the reality is there just isn’t built capacity that’s available. These are technically complex facilities, there’s not an infinite number of people who know how to set them up. And the supply chain for the machines that make the products is also constrained” (2).

An interesting ironic side note is that Catalent has had a checkered compliance past. FDA visited the company’s Brussels plant in October 2021 and August 2022. Reuters reported that “inspectors said the lapses at the plant … represented the most serious form of violations, according to the reports, which show Catalent shut the facility down twice between the two inspections” (3). Reuters goes on to say, “at a meeting with Novo executives in May, two investors out of a group of about five expressed concerns about the choice of Catalent as manufacturing partner, citing the contractor’s history of compliance issues with FDA, according to one of the shareholders who was present. The investor, who declined to be named due to the sensitivity of the matter, said Novo’s Chief Financial Officer Karsten Munk Knudsen had responded by saying that, in hindsight, the company may have made a mistake in choosing Catalent and was now tightly overseeing the firm’s filling operations of Wegovy in Brussels” (3).

Novo Nordisk and Eli Lilly are spending heavily to boost their manufacturing capacity. “That could help them fend off competition from specialized pharmacies that are making generic versions of semaglutide and tirzepatide, an option created by the FDA designating the drugs in shortage” (2). Nevertheless, Anat Ashkenazi, Lilly’s chief financial officer, said in the Post article, “we intend on holding Catalent accountable to their contract with us” (2). Given new ownership, its uncertain if Lilly will be first in line, on the production line.

Catalent. Novo Holdings to Acquire Catalent. Press Release. Feb. 5, 2024.

Gilbert, D. Makers of Ozempic, Mounjaro Race to Meet Demand for Weight-loss Drugs. 

Fick, M. Insight: Wegovy Weight-loss Injection Factory Plagued by Sterile-safety Failures.

When referring to this article, please cite it as Hennessy, M. First in Line on Catalent’s Line. 

While Catalent’s acquisition is definitely about making drugs, it’s also very much about making money.

First in Line on Catalent’s Line

Given its positioning at each new year’s commencement, the J.P. Morgan Healthcare conference helps establish the tone with which the pharmaceutical industry is viewed. It is rare for major new announcements to be made at the conference; rather, its prominence is due to its capacity to sum up and condense the lessons learned from the past year’s fray.

As such, both Lisa Gill, senior analyst covering Health Care Services, and Chris Schott, senior analyst at J.P. Morgan covering US Diversified Biopharma, emphasize the salience of the current generation of weight loss drugs. Schott stated that, from an investment perspective, due to pharmaceuticals underperforming in 2023, “investor sentiment is pretty bearish for 2024 … as [the sector] is a well-positioned group, at record low valuations” (1). Schott goes on to say, “the GLP-1 weight loss drugs are projected to hit $100 billion in prescription sales by early 2030s, making it the largest therapeutic market we’ve ever seen, … and to alleviated bottlenecks, production capacity is expected to double in 2024, and rise again by 50% in 2025” (1).

While recaps are certainly useful, it is salutary to point out 

 was investigating GLP-1 performance in 2022, and asking, are obesity drugs the next blockbusters? 

 pointed out, “Novo had to revamp its production due to high demand for Semaglutide and some setbacks with manufacturing facilities. Overall, reliable API suppliers and contract manufacturing organizations (CMOs) are key factors in market success. Indeed, to solve such potential manufacturing obstacles, many companies opt to build in-house capabilities instead of relying on CMOs. Novo decided to build three new manufacturing facilities. This step will increase manufacture of its APIs, while also being able to assemble and package the oral and injectable products.” Necdina further emphasized potential production bottlenecks saying, “Eli Lily, a new potential player in obesity market, seems to understand manufacturing challenges. They plan to expand manufacturing footprint in Indiana by investing $2.1 billion in two new manufacturing sites” (2).

Gill, L; and Schott, C. 42nd Annual J.P. Morgan Healthcare Conference, J.P. Morgan Health Events website, 

https://www.jpmorgan.com/about-us/events-conferences/health-care-conference

Necdina, M. Are Obesity Drugs the Next Blockbusters? 

When referring to this article, please cite it as Hennessy, M. J.P. Morgan Losing Weight. 

Given its positioning at each new year’s commencement, the J.P. Morgan Healthcare conference helps establish the tone with which the pharmaceutical industry is viewed.

J.P. Morgan Losing Weight

In June 2023, FDA Commissioner Robert Califf ascribed most drug shortages to “generic-drug companies going out of business, either because they fail to invest in quality operations or because they can’t make a profit, as hospitals and pharmacies seek lower prices” (1). Chris Spivey, editorial director of 

®, wrote about Beyfortus being in shortage partly because of unanticipated high demand, but also pediatric practices. Unsure of reimbursement timelines and amounts, it experienced a vaccine hesitancy of the financial kind. Pediatric practices didn’t want to hold on to lots of $500 a shot doses (2).

On Dec. 5, 2023, the US Senate Finance Committee held a hearing on drug shortages. Marta Wosinska, senior fellow at the Brookings Institution, testified that generic sterile injectable (GSI) drugs represent about half to two-thirds of all shortages. GSI shortages result from how hospitals buy GSI drugs, and the underinvestment in manufacturing operations that follow. Wosinska stated GSI shortages result primarily from “manufacturing quality problems at facilities where the final product is made, often in the United States … What is vexing about those shortages,” she continued, “is that they are largely avoidable. All payers, including Centers for Medicare and Medicaid Services (CMS), reimburse hospitals in ways that give them incentives to use the lowest-priced GSI drug available … The price pressures put on manufacturers create a dynamic where there is little room for—or little return on—investing in manufacturing facilities, staffing, and oversight. [GSI drugs are hard hit] because making those drugs requires specialized facilities where employees follow complex manufacturing processes and controls. If we want to address the persistent GSI drug shortages, CMS will need to pay hospitals differently, incentivizing them to consider reliability of supply in their purchasing decisions … CMS does not have the authority to set up such a program, especially one that is not budget neural. This Committee however can grant that authority” (3).

Wechsler, J. Drug Shortages Continue to Plague FDA and Manufacturers. 

Spivey, C. Why We Were Not Properly Winterized for RSV Season. 

Wosinska, M. Testimony before the Senate Finance Committee, December 2023.

When referring to this article, please cite it as Hennessy, M. Reimbursement Precipitating Shortages. 

GSI shortages result from how hospitals buy GSI drugs, and the underinvestment in manufacturing operations that follow.

Reimbursement Precipitating Shortages

Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation. It will not be an easy process. It’s an evolution long in the making and welcomed for not only improved treatment outcomes, but also for increasingly realistic “cures”. In such a tightly regulated space, where large financial investments are also required, many unwilling stakeholders will be swept along with this rising tide of new medicines. Who would have seriously considered larger-scale three-dimensional printing of medicines five years ago, or marrying messenger RNA delivery methods with chimeric antigen receptor therapies for reconfigurable patient specific antigen profiles, within the same patient, over the span of a month?

To keep this surging tide heading into workable spaces without swamping all systems, international bodies, such as the International Council for Harmonisation and the World Health Organization, are going to have to be relied on to perform much of the heavy lifting. New financial cooperation models, some of which were trial ran during the COVID-19 pandemic, must also be implemented for consolidated gains to remain real.

With these advances rolling in at a more rapid pace than ever before, our coverage of the pharmaceutical space must also evolve. This year, we have increased our coverage of the daily news, to provide insight at a greater pace. The brand has also rededicated to video coverage, to provide insight from the experts on the frontlines of these advances. Along with these changes, we have amped up our conference coverage, to provide key advances and learnings from major meetings throughout the year, like our coverage from the 11th International mRNA Health Conference and CPHI Barcelona. All these latest insights can be read at 

As we eye up trends and opportunities for 2024, we are truly excited for the fruits of the future. There is so much awaiting us, and we can be guaranteed that the new medicines about to be manufactured, stored, delivered, and received will be more efficacious than ever and worth the efforts. And that is something worth holding on to, something to be proud of.

When referring to this article, please cite it as Hennessy, M. The Dislocation of Progress. 

Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation.

The Dislocation of Progress

As of mid-October 2023, there were 9342 clinical trial studies targeting COVID-19 (1). This is alongside 12,086 patents that relate to COVID-19 (2). Messenger RNA (mRNA) clinical trials, however, stand at only 483, with 112 related patents. mRNA was the talk of the industry during October 2023, as Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their work in mRNA vaccines against COVID-19.
In an interview with Pharmaceutical Technology®, Laks Pernenkil, Principal and Practice Leader, US Life Sciences, Deloitte, pointed to “an emphasis coming out of the pandemic on supply resilience … with all the ups and downs around the supply of raw materials, there has been significant focus on ensuring patients are not affected by supply shortages, part of the anxiety has manifested around inflation [rising costs] of raw materials.” Pernenkil also drew attention to increased digitalization as improving process design, supply performance, and eventually, profits (3).
At the other end of the spectrum, discovering new types of drugs and therapies, the top five pharmaceutical companies’ investments in R&D in 2022 were Roche with $14.78 Billion, J&J $14.14 billion, Pfizer $12.38 billion, Merck $11.84, and BMS $10.02 billion, ranging between 15% to 30% of income (4). Such investment speaks of self-confidence and perhaps aligns with increasing trust in the newest modalities, including mRNA approaches.


NIH. https://clinicaltrials.gov. Clinical trials.gov (accessed Oct. 12, 2023).

World Health Organization, WHO’s Covid-19 Response Timeline (accessed Oct. 12, 2023).

Playter, G. The Era of Digital Data in Bio/Pharma Manufacturing. 

Statista. Leading 50 Global Pharmaceutical Companies by Prescription Sales and R&D Spending in 2022. 

When referring to this article, please cite it as Hennessy, M. Capitalizing on Success. 

Industry investments indicate increasing trust in the newest modalities, including mRNA approaches. 