Grant Playter

, a biotech start-up focused on regenerative medicines. In this candid discussion with Grant Playter, associate editor, Luis discusses his company’s regenerative bone therapy, how it evolved from his experiences in Iraq, how Theradaptive secured funding in a lukewarm venture capital market, and more.

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Luis Alvarez, PhD, founder of Theradaptive, candidly discusses how his regenerative therapy start-up evolved and secured start-up funding.

Unpacking Regenerative Medicines and Start-Up Funding with Luis Alvarez

The United Kingdom Bioindustry Association recently released new data surrounding UK biotech funding in the second quarter. According to the report, venture capital investments rose from £258 million in the first quarter to £338 million in the second, whereas public funding rose from £37 million to £44 million. This represents an overall quarter-over-quarter uptick of 29%, putting it en route to approximately match the £1.21 billion raised over the course of 2022. However, both years totals are set to lag significantly behind 2021, which saw approximately £2.52 billion in total financing.

According to findings from the report, the average size of venture capital investments in the second quarter was £13 million, the same as the first. The report also noted that there was a “healthy spread” of funding between early- and late-stage companies.

The report summary stated that public markets remain challenging, with no new market launches or lackluster follow-on funding, a trend noted as in-line with international trends; no UK biotech company raised money via initial public offering (IPO) in this quarter, mirroring the first quarter. This is in stark contrast to 2021, which saw approximately $1.3 billion raised via IPO over the course of the year. However, due to the positive momentum of the quarter and overall stability in attracting capital, as well as upcoming UK government policy initiatives set to bolster funding, the overall findings were deemed positive by the members of the UK Bioindustry Association.

“Amidst the current challenges facing the UK’s biotech sector, we are encouraged by the 29% growth in investment quarter-on-quarter, and the positive policy progress from UK Government that bodes well for a rapid rebound.” said Steve Bates, CEO, Bioindustry Association, in the report.

The summarized findings of the report can be read 

Articles

A report from the UK Bioindustry Association report indicated that biotech venture and public financing rose from £295 million in the first quarter to £382 million in the second quarter.

United Kingdom Biotech Report Finds 29% Uptick in Funding

Cytomos, a Scottish life science company focused on developing new approaches to analyzing cells, announced on Aug. 9, 2023, that it had secured £4 million (approximately $5 million) to scale-up market testing of its technology platform Cytomos Dielectric Spectroscopy (CDS). According to a company press release, CDS is designed to provide high-speed, scalable, and low-cost cell analysis relative to existing systems.

The investment round was led by existing investors Archangels, as well as participation from Old College Capital, Scottish Enterprise, and new investor British Business Bank. According to the release, the new investment will allow Cytomos to significantly advance the development of CDS and expand its team. The company is targeting platform commercialization in 2024.

“On the back of a very successful year for Cytomos, this new funding will now allow us to scale up our engagement with industry partners,” said David Rigterink, CEO, Cytomos, in the release. “We truly believe that, through our CDS technology, we offer a powerful platform which will help the scientific community bring novel therapies to market faster and radically reduce costs by making better informed, game-changing decisions a lot earlier.”

“As a highly innovative, Scottish early-stage life science company with global horizons, Cytomos is an excellent fit for our investment portfolio,” said Sarah Hardy, director and head of new investments, Archangels, in the release.  “Its ambitious vision to improve real time cell analysis in formats to better suit the end users will revolutionize the development and commercialisation of products in the bioprocessing and cell and gene therapies spaces.  We’re looking forward to working with David and the team as they drive the business forward, making smarter, faster and more accurate cell analysis finally more accessible.”

Cytomos will use the £4 million in funding to develop its dielectric spectroscopy technology.

Cytomos Secures £4 Million to Develop Spectroscopy Platform

Waters Corporation announced the launch of the XBridge Premier GTx BEH size exclusion chromatography (SEC) columns on August 1, 2023. The new SEC columns are designed to improve analysis while lowering the cost of gene therapies, specifically for adeno-associated viral (AAV) vectors.

According to a company press release, the columns aim to reduce the cost of gene therapies by using 3 to 10x less sample, generating faster results, and offering more drug substance information. Additionally, a new multi-attribute quantification method is intended to double analytical speed, quadruple sensitivity, and increase resolution of target analytes by up to 50%.

According to the release, SEC is a technique used for aggregate and fragment analysis in the research, development, and manufacturing of biotherapeutic proteins, such as insulin and monoclonal antibodies. The Xbridge columns are designed to take robust physicochemical characterization and quantitative measurements. Aiming to double the speed of measuring the potency and safety of AAVs, the SEC columns are intended for process development, formulation studies, regulatory filing support, ongoing process monitoring, and quality control.

"We are witnessing a revolution in medicine thanks to gene therapies like AAVs," said Erin Chambers, vice-president, Consumables and Lab Automation, Waters Corporation, in the release. "A small quantity of a gene therapy, such as one of the best-selling eye treatments, can retail for more than $400,000 per eye. This makes it imperative that process and formulation development tests measure multiple attributes of the drug at once while consuming as little of it as possible. It's why Waters' low adsorption … SEC columns are such a good choice for process development, formulation studies, regulatory filing support, along with ongoing process monitoring as well as quality control."

Waters XBridge Premier GTx BEH size exclusion chromatography (SEC) columns are designed to improve analysis while lowering the cost of gene therapies.

Waters Launches SEC Columns for Gene Therapy Applications

Kiefel, a German company specializing in thermoforming and joining technology, announced the launch of its Solutionperformer KFS modular form-fill seal machine on August 3, 2023. According to a company press release, the machine is built to form, fill, and seal up to 6,000 infusion, parenteral nutrition, or dialysis bags per hour. It is available in both standardized and individually configurable solutions.

According to the release, the line manufactures, fills, and seals the bag on a single machine. Bags can be customized from sizes of 50 to 6000 ml. Precision mass flow meters, optional residual oxygen content control, and automatic sealing of the bags are intended to ensure maximum output combined with constant quality monitoring.

"With the [Solutionperformer] we have developed a new generation of a modular and optimally coordinated machine concept," said Thorsten Emge, global director, Medical & Pharma, Kiefel, in the release. "With the best price-performance ratio, it meets the high requirements of our customers in terms of output, efficiency and bag quality."

Kiefel’s new machine is designed to form, fill, and seal up to 6,000 infusion, parenteral nutrition, or dialysis bags per hour.

Kiefel Launches Modular Form-Fill Seal Machine

The arrival of the first messenger RNA (mRNA) vaccines to the market ushered in pharma’s honeymoon period with the technology. After more than 50 years of research (1) into the technology, the ongoing COVID-19 crisis allowed the vaccines to immediately prove their effectiveness on the global stage. Consequently, a veritable gold rush has kicked off, as companies such as Moderna, Pfizer, and Sanofi have begun clinical trials for various types of mRNA vaccines. Moderna, in particular, is evaluating the clinical potential of mRNA vaccines for myriad conditions, including influenza, Zika virus, respiratory syncytial virus, human immunodeficiency virus (HIV), cytomegalovirus, and even cancer (2).

However, as the luster of mRNA vaccines shines brighter than ever before, it is worth considering how these products factor into the greater vaccine marketplace. This article will unpack the unique attributes of mRNA vaccines, how they compare to traditional alternatives, and what use cases they are suited for.

At a basic level, mRNA vaccines function by inserting an mRNA strand that corresponds to a viral protein, allowing cells to produce viral proteins and produce antibodies. This is not dramatically different from how conventional vaccines work (i.e., by inserting a scientifically weakened version of the virus as an antigen into the body), in principle, but in practice there are a few key differences that made mRNA vaccines invaluable in the fight against COVID-19.

Chief among these differences is the speed of development and delivery. Traditional vaccines need to be grown and cultivated in vessels such as chicken eggs or mammalian cells, and this process of collecting the virus can take months. Conversely, according to a Pfizer informational page, it takes approximately one week to develop an experimental batch of an mRNA vaccine, greatly accelerating time-to-test. In a similar vein, the delivery process can be simplified and accelerated because DNA can be synthesized from a digital sequence (3).

In this regard, mRNA vaccines simplify aspects of the vaccine production process that enable greater flexibility and adaptability. Jeff Fischer, president and co-founder of Longhorn Vaccines & Diagnostics, discussed the merits of this process at length in an episode of 

®’s Drug Solutions Podcast (4). While broader use cases exist, Fischer honed in on mRNA vaccines as particularly useful in the use of personalized vaccines, like those being developed for cancer, because of their quick development time and highly flexible nature.

“I think that the mRNA vaccines [are] going to have a lot of applicability in cancer, in some areas where you’re not necessarily looking for long term [durability],” said Fischer. “And in the case of Moderna, working with Merck, where you’re adding it with a drug, and you’re allowing the vaccine to do
part of the work and you’re allowing the drugs to do the other part of the work, I think that there’s going to be a real focus there.”

However, while the benefits of mRNA vaccines have been proven, there are relevant questions concerning ideal use cases because of questionable durability response. Because of the relative novelty of mRNA vaccines, there is a lack of detailed scientific data on the issue. However, what has been observed may deflate some who view mRNA vaccines as a wonder drug.

FDA approval of various booster doses is contingent on clinical trial data that demonstrate significantly increased immune response. For instance, Moderna’s COVID-19 Omicron variant-containing bivalent booster candidate achieved approval when data showed that it exhibited an eight-fold boost in neutralizing geometric mean titers against omicron among
seronegative participants (5).

However, while initial effectiveness is not in dispute, later studies have shown a lack of durable response in mRNA booster vaccines. For example, one study found that, while boosters—in this case, the third and fourth booster shots for both the Pfizer-BioNTech and Moderna COVID-19 vaccines—did demonstrably increase antibody titers following the initial two-dose vaccination, “only 45% to 65% of participants demonstrated a detectable nAb [neutralizing antibody] titer against the newer variants after the booster (third dose)” (6). The study also showed that the immune response declined to below the detection limit in almost all individuals by six months. The study thus concluded that the durability of serum antibody responses only improved marginally following booster vaccines (6). A similar study recommended the use of boosters six-to-eight months after vaccination (7), which is similar to how booster vaccine roll-out ultimately occurred.

“I think that the industry was a little bit surprised by the lack of durability of the mRNA vaccines; I don’t think they could have predicted that,” said Fischer in the podcast interview. “I think there was a rush to now throw everything into the mRNA bucket. And then the same thing was true, I think of the adenovirus-based vaccines: there were some good things seen at small scale, but when you took them up to [significantly] large populations, then you started to see some safety issues that now are putting adenovirus-based vaccines into a black box.”

To many, this degraded response may seem self-evident—even accounting for the existence of variants and mutations to the original virus strain, the need for booster vaccines in and of itself implies some degree of degraded response. However, even if the initial immunization response persists in some form or fashion, a degraded response to vaccines that are not typically administered on a year-to-year basis would not be optimal for many conditions.

One-and-done vaccines, such as those for polio and measles, have significantly higher odds of reaching those who are vaccine hesitant or simply too busy to continue receiving vaccines. The Centers for Disease Control and Prevention currently estimates that while approximately 270 million Americans, or 81.4%, have received at least one dose of a COVID-19 vaccine, the amount who have received the most recent updated bivalent vaccines is approximately 56 million, or just 17% (8). And while COVID-19 vaccines have been shown to remain effective against severe infection even without boosters (6), the underlying technology may not be suitable for diseases where infection must be avoided.

While mRNA vaccines are a proven breakthrough, until the concerns surrounding durable response can be definitively answered, their use case must be narrowed to conditions where a diluted infection is an acceptable outcome, such as yearly influenza, or where the goal is complementary treatment, such as personalized cancer vaccines. While this may fall well short of the “wonder drug” status many are keen to assign these products, mRNA vaccines nonetheless seem poised to transform a significant pharma market segment.

1. National Institutes of Health. Decades in the Making: mRNA COVID-19 Vaccines. 

2. Billingsly, A. More Than COVID-19: 6 Other Promising mRNA Vaccines in the Pipeline. 

3. Pfizer Staff. What Makes an RNA Vaccine Different from a Conventional Vaccine? Pfizer, May 5, 2020.

4. Playter, G. Drug Solutions Podcast: Evaluating the Vaccine Marketplace.


5. Moderna. Moderna Announces Omicron-Containing Bivalent Booster Candidate mRNA-1273.214 Demonstrates Superior Antibody Response Against Omicron. Press Release, June 8, 2022.

6. Arunachalam, P. S.; Lai. L.; Samaha, H.; et al. Durability of Immune Responses to mRNA Booster Vaccination Against COVID-19.

7. Korosec, C. S.; Farhang-Sardroodi, S.; Dick, D. W.; et al. Long-term Durability of Immune Responses to the BNT162b2 and mRNA-1273 Vaccines Based on Dosage, Age and Sex. 

, 2 (1), 21232. DOI: 10.1038/s41598-022-25134-0

8. Centers for Disease Control and Prevention. COVID Data Tracker. 

Pharmaceutical Technology
Vol. 47, No. 8
August 2023
Page: 26-27

When referring to this article, please cite it as Playter, G. Charting the Future of Vaccines. 

A comprehensive understanding of what makes mRNA vaccines tick is crucial in charting the future of the market.