The 4 steps of our market validation analysis

As all of you know, we develop services for supporting technology transfer operations in research-based institutions such as universities and research centers. After a year, we have talked to more than 200 of these organizations to better understand their needs, their pains, and how could we develop a service that fits their demands.

TTOs are responsible not only for the commercialization and licensing out of patents and technologies, but also spin-off creation, contract management, writing technology offers, and many other complex bureaucratic tasks.  Furthermore, we have noticed that many universities TTOs are usually understaffed, considering the great number of technologies they receive, which normally are from completely different fields. Apart from this set of tasks, we cannot forget that they are also responsible for maintaining and creating new collaborations and relationships with industry actors and external companies. To create these connections is extremely time-consuming and many TTOs do not have left enough time to invest in this. The result of this is a research-based institution with the research, contractual and legal capabilities, but disconnected to the industry, lacking entry points in companies and struggling to validate the need for their technologies in the market. 

To address this issue, at Viromii we have developed a service that alleviates these pain points. This service has the objective of presenting a given technology to decision-makers at the most relevant companies with potential to acquire this technology. During the project, we aim not only to validate the commercial value of a technology or close a licensing deal, we create bridges and close the gap between the industry and the TTOs. The process consists of 4 steps:

Additionally, we have seen that besides checking on the interest of potential licensees, we have been able to communicate the capabilities of the research groups for future technology developments; we have broadened the network of contacts in companies of the TTOs; and with this information we have been able to device more actionable strategies on where to extend the patents and which patents have more potential to be patented. 

We hope you found this interesting, and we are happy to have a meeting and give you more info if you feel this could be a good fit for your research institute or university.

Phage therapy, the solution for multiresistant bacteria?

Recently, at Viromii, we have been working on a really interesting project regarding phage therapy, a promising area that can help to overcome the problem of multiresistant bacteria. We found the topic exciting, and we want to share some of our insights.

Phage therapy, or bacteriophage therapy, consists of using phages to treat bacterial infections. Before the antibiotic era, phages were used to treat infections, usually, a cocktail of phages was administered to patients suffering from a bacterial infection. This was used because phages are super-specific, a phage recognizes and infects a specific strain or even sub-type of bacteria, by introducing its genome inside it. Then, this genome uses the bacteria replication mechanism to generate a new virus, which from inside destroys the bacteria through the secretion of lysines, also called endolysins.

After antibiotics were discovered and successfully used as antimicrobial agents, the use of phages as therapeutics was abandoned in many parts of the globe, although in East Europe or Russia its use has somehow continued. The reason why phages were abandoned was that antibiotics have a wide spectrum of activity and the same antibiotic could be used to kill a great number of different bacteria. Therefore, with antibiotics there is no need to identify the pathogen to initiate the treatment; instead, with phages, the specificity obligates to either identify the pathogen and then administer the specific phage that will recognize it or to use a cocktail of thousands of different phages, which is not optimal at all. The use of a phage cocktail can have a positive effect but does not assure it, in some cases it can turn to be a problem. Moreover, large-scale production and purification methods were easier to design for antibiotics than for phages, it seemed obvious that antibiotics were the choice.

However, the problem of multiresistant bacteria has put phages in the scene again. The inconvenience associated with specificity also has an advantage in this sense, as the fact of only recognizing and targeting a specific type of bacteria minimizes the possibility of creating multiresistant bacteria or affecting the “good” microbioma. This, along with the advancements in high-throughput sequencing technologies and bioinformatics is encouraging companies to investigate the possibility of using phages as therapeutics. The market potential is really big, in 2017 the global antibiotic market reached 42.000 million $US and it is expected to reach 65.000 million $US by 2026; if phages become a real alternative they can take part of this market and the first companies who develop efficient solutions, screening methods, and large-scale production, will gain a favourable position and get a big piece of the cake.

The race has started. Since 2000, the patent activity in the field has increased, as well as scientific publications. A quick view to patents and scholar publications shows how the importance of phage therapy has increased exponentially, and it seems it will continue.

Looking at patenting activity, we could identify many companies, among them here we list some of the most interesting ones are:

• Intralytix: discovery, production and marketing of bacteriophage-based products to control bacterial pathogens in environmental, food processing, and medical settings
• Phico Therapeutics: developed a new class of antibacterial agent, a platform technology called SASPject, disabled bacterial viruses.
• Phermecydes Pharma: developing precision phage therapy to treat bacterial infections

At Viromii, we are keeping track of the field. Hopefully soon, we will see commercial therapies based on phages in the market, saving lives while avoiding the creation of multiresistant bacteria. There are still many advancements to be done, but companies are working hard and capital is being invested, so it is a matter of time until these therapies reach the market.
If you want to know more about this, or related areas, please feel free to reach out as we are more than willing to talk with you!

Sources:

Charles Schmidt. Phage therapy’s latest makeover. Nature Biotechnology volume 37, pages581–586 (2019).

Furfaro LL, Payne MS, Chang BJ. Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles. Front Cell Infect Microbiol. 2018;8:376.

https://cmr.asm.org/content/32/2/e0006618

https://www.grandviewresearch.com/press-release/global-antibiotic-market

https://www.alliedmarketresearch.com/antibiotics-market

Innovative strategies for extending drugs’ market exclusivity

In the previous post, we explored the different preventive strategies pharma companies use to maintain their market exclusivity. At Viromii we feel this is a really interesting topic and in this post, we will continue the discussion by explaining the different innovation-linked strategies extracted from the article by Chie Hoon Song and Jeung-Whan Han “Patent cliff and strategic switch: exploring strategic design possibilities in the pharmaceutical industry.”

Innovation strategies focus on outpacing the competition by actively provoking shifts in the industry evolution and setting new market “rules” that competitors must constantly adapt to. Product-related examples of these strategies are product line extensions, approval of new indications, introduction of follow-on products, or prescription-to-OTC switch. These product-related examples all build upon current company’s assets and create new market opportunities. In the following lines, the previously mentioned examples will be further explained for a more comprehensive view.

Product-line extensions: These extensions can be better understood as proactive variations of existing products with the aim of making a more complete or advanced product. Examples include further purifying the product, lowering the costs of production through more modern production technologies, or creating superior formulations of already existing medicines. Here are some real-life examples of these strategies:

• Eli Lilly Prozac ® expired on 2001, so they obtained a patent for its combination with olanzapine and created Symbyax ® for refractory depression, moving the patent expiration year to 2017.
• Pfizer’s Procardia XL® is built upon a previous drug but with a new controlled-release formulation for the treatment of arterial hypertension.

Indication extension: This extension is a very “trendy” way of innovating in the drugs and molecules markets and refers to the practice of identifying new ways of application for already existing or expired molecules. This method really facilitates the regulatory process, which makes it of high interest for smaller companies. If the new clinical trials for the newly found indication appear to be promising, an extension of the drug approval may be requested. This way, the innovative company can gain three extra commercial exclusivity years, while at the same time extending their drug to new markets. There are thousands of examples of this process, including the one presented below:

• Eli Lilly’s Adcirca® was found to be useful with erectile dysfunction, so they created Cialis®. After some years of research they found a new dosing that was valid for benign prostatic hypertrophy and got that indication, granting them several extra years of commercial exclusivity.

Prescription-to-OTC switch*: This switch happens when a company accomplishes the removal of the active component from prescription only status. Therefore, by usually reducing the active component dose on the new OTC form, they open a new expansive market segment. The reasons behind these decisions vary, and may include less price negotiation, bigger patient base that can access the component, and, of course, the use of the brand loyalty from the previous prescription medicine to leverage on. There are risks and difficulties however. Obtaining OTC status usually requires very high proof of safety and high investment in marketing and advertising, which requires a big business adaptation since OTC products are very different from a prescription product. One important example of this switch can be found with the adaptation of drugs for muscular pain into topical gels.

* OTC: Over-the-counter drugs, drugs sold directly to the consumer, without the need of a prescription.

Business model strategies: These strategies involve many changes in the structure and governance of the way a company creates and captures value. In this case, adaptation is a must, and a company has to have their eyes wide open to be able to perceive changes in the market to quickly adapt to them. An example of this is the change in the paradigm that occurred when exploring and discovering NME (new molecular entities). As the prices and early regulatory processes increasingly became risky and costly, many companies began to adapt new business models based on licensing, ad-hoc commercialization, or acquisition of smaller firms that are more advanced in the regulatory process for their molecules. A simple example that we already discussed in our previous post is the case of the pharmaceutical company, Shire that decided to focus on rare diseases since it was a very niche field with big regulatory and exclusivity advantages.

We hope you enjoyed the read and will keep you updated with future posts. Follow us to know more!

Sources:

Song, C. and Han, J. (2019). Patent cliff and strategic switch: exploring strategic design possibilities in the pharmaceutical industry.

Preventive strategies for extending drugs’ market exclusivity in the US and EU

In the previous post we could see the greatly negative impact that losing market exclusivity has over the financials of pharmaceutical companies, specially when it was about a blockbuster drug. This leads us to think, what can pharma companies do to placate such sales impact? Well, there exist a number of strategies these companies can implement to minimize the harm of losing the exclusivity of one of their drugs. In this post we will go over them, so check it out.

Pharma companies usually file patent applications for their drugs as early as possible, mainly because they know that it is common for other companies to be conducting research in similar indication areas and drugs. However, this approach has the risk of expiring the patent way before optimal, as drug development is a very slow practice taking on average 12-13 years to complete research, development and achieving regulatory approval, and leaving just 7-8 years for proper commercial exploitation with exclusive patent rights. This, usually leads to insufficient time to achieve a positive revenue on the investment made for the R&D of the drug.

There are four main strategies that pharma companies usually implement to aplacate the “patent cliff” (loss of exclusivity leading to a drop in the revenues from a certain drug), which include preventive, innovation, extraction and adaptation strategies. In this post we will focus on preventive strategies.

Preventive strategy basically implies the exploitation of possibilities for extension of market exclusivity mostly by means of legal measures. Examples of this are:

• Strategic patenting: where the company files multiple patents to provide with longer time of protection of core parts of the drug surrounding the base patent. This practice is named patent clustering. Acquisition of secondary patents apart from the main active drug compound or ingredient. For example filling for crystalline forms derived from the original compound, methods of administration, formulations, etc. This is also applicable for patents in the manufacturing process, where the protection of some purification or process optimisation can be possible at later stages of product lifecycle, hence either complicating or simply extending the product exclusivity life. Incremental improvements to the primary patent in form of secondary patents might provide with extended exclusivity for the drug in the market. One example of this strategy in use is Ritonavir (for HIV) which created a great cluster of secondary patents granting up to 12 years of extra protection to their drug against generic products. The ratio of primary to secondary patents is 1 primary to 7 secondary patents. Though this practice might be sometimes successful stopping generic entry, stricter patentability standards are making the patent cluster strategy more and more vulnerable.

• Another preventive strategy to deter generic entry is to apply for market exclusivity extensions through supplementary protection certificates (SPC). SPCs are additional protective mechanisms that work as an extension of the patent right. In EU, SPCs are usually issued to compensate R&D costs and the usually too long period between the patent filing and the market authorization. This certificates can extend up to 5 years the products after the expiration of the patent. However, same as with patents, SPC extensions can be legally challenged and invalidated. The analogous in the US and Japan are the PTR (Patent Term Restoration) which grants with additional 5 years of protection upon patent expiration.

• In the US, there also exist a legal option to get 30 additional months of exclusivity by filing a patent infringement suit against an ANDA(abbreviated new drug application, which usually applies for generic drugs). The 30-month stay is applied when a patent infringement action is initiated and the patent information was submitted to the FDA before the generic drug application was submitted.

• Getting orphan drug status can extend up to 7 years your exclusivity in the US, and 10 in the EU. However, this designation will just be issued for drugs that target rare diseases, which must be life-threatening or chronically debilitating, and cannot affect more than 5 patients in 10.000, not existing other adequate treatment. Other advantages of this status are fast-track approval and tax credit. This strategy has been implemented by a number of pharmaceutical companies, being Shire Plc (now part of Takeda)  one of the most well known examples of company strongly focused on development of drugs focused on rare diseases.

• Similar to orphan drug status, application for pediatric clinical trials on the FDA might grant up to 6 months of extended protection.

• Finally, if generic entrants challenge the validity of the patents held by the innovative company, they might reach an out-of-court settlement which can include a substantial payment (covering their potential sales in case the generic would have made it to the market). The main risk of this practice is competition law, as the OECD can issue considerably high fines for infractors.

In the following posts we will explore the next strategies. We hope you enjoyed the read and learned something new. Follow us to know more!

Sources:

– Song, C. and Han, J. (2019). Patent cliff and strategic switch: exploring strategic design possibilities in the pharmaceutical industry.

– American Pharmaceutical Reviews (https://www.americanpharmaceuticalreview.com/Featured-Articles/348913-Intricacies-of-the-30-Month-Stay-in-Pharmaceutical-Patent-Cases/)

When pharma companies lose control and exclusivity over a blockbuster

Lately, at Viromii, we have been working with some really interesting projects in the pharma industry, this has made us look a lot to patents, commercial rights and mechanisms to prolongate exclusivity over a molecule or drug. We have decided to start a series of posts on the topic and this first post is aimed to be the base for the following ones.

As at the beginning of every year, the list of drugs losing exclusivity during 2019 has been released. This year, Roche is the company that can suffer the biggest impact, as their exclusive rights to commercialize Rituxan, Herceptin and Avastin are at stake. Relevant patents covering Rituxan lapsed at the end of 2018 and competitors are ready to launch their biosimilars; in fact, in Europe sales of Rituxan (MabThera in Europe) dropped by 47% in 2018, after Sandoz and Celltrion started to commercialize their biosimilars.

Pharmaceutical companies invest and fight hard for keeping their exclusive commercialization rights over their blockbusters, when a generic enters the market sales can drop dramatically, some estimations show that in average sales can decrease between 37% to 48%, this is, for example, the case of Pfizer’s Lipitor® one of the bestsellers drugs worldwide in the history. In 2012 Pfizer lost commercial exclusivity (always keeping in mind that the timing varies among countries and legislations) over Lipitor® and soon generics were launched; this created a huge drop in sales, Lipitor® went from generating revenue of around $9.5 US bn in 2011, to $3.9 US bn in 2012, a decrease of 59% in revenues.

Lipitor® is one of the many examples, at some point all drug developers face the issue of losing control over their drugs, and therefore these companies have developed many strategies aimed to keep control and extend the exclusive rights over their blockbusters. Drug developers fight to stop generic introduction at the level of days; continuing with the example of Lipitor®, from 2011 to 2012, in only one year, the revenues dropped $5.6 US bn, which means $15.3 US million per day, $460.3 US million per month. These numbers are huge and can have an important impact on the financial statements of any pharma company, therefore they put a lot of effort, and sometimes get really creative, when trying to prolongate their exclusivity. There are different mechanisms available, ranging from creating a patenting strategy that allows to file later patents covering different aspects of the base compound of the drug, filing a patent infringement suit, extending the therapeutic use of the drug by finding new indications or, if possible, applying for orphan drug status. These are only some examples and different strategies suit better different cases, as well as the geographic scope and applicable legislation will make drug developers chose one mechanism or another.

At Viromii we have been lately investigating these mechanisms and discussing with different pharma experts in the field, in the next post we will go deeper in explaining these mechanisms and its consequences, so, if you are interested, keep tuned.

Sources:

Fiercepharma (https://www.fiercepharma.com/special-report/top-pharma-patent-expirations-2019).

Biopharma International (http://www.biopharminternational.com/strategies-extending-life-patents)

Song CH, Han JW. Patent cliff and strategic switch: exploring strategic design possibilities in the pharmaceutical industry. Springerplus. 2016;5(1):692. Published 2016 May 23. doi:10.1186/s40064-016-2323-1