Open Innovation and CROs
The globalization of research
Never before at such a scale, nor more united across a common goal, have scientists around the world worked together to bring a vaccine to the market at record speed. With every successful vaccine story built on a collaboration – Pfizer and BioNTech, AstraZeneca and Oxford University, or in Italy, Takis Biotech and Rottapharm Biotech – open innovation is getting closer to becoming the status quo of biotech research. Fostering an open innovation climate is Italy’s best chance in driving its ideas, be them in pharma, biotech, or med-tech, into the market. In Europe, about 20% of all research takes place outside corporate boundaries, through the interim of universities, SMEs, start-ups, clinical centers, or CROs, according to Farmindustria. In Italy, a few high-profile collaborations in the biotech space come to mind, such as Dompè’s partnership with the Universities of Chieti and L’Aquila in the development of the first ever biotech therapy to treat neurotrophic keratitis, a rare disease affecting the eye cornea, and which can lead to blindness. Italy has also developed prolific hubs in support of open innovation, such as the San Raffaele Biomedical Science Park, one of the largest in Europe, or, soon to be opened MIND (Milan Innovation District), a multi-disciplinary smart-city waiting to receive about 60,000 researchers in the next eight years.
One of the most successful Italian open innovation stories is Holostem Terapie Avanzate, a spin-off from the University of Modena and Reggio Emilia that partnered with large Italian player Chiesi. Holostem was founded in 2008 and is the first biotech company fully devoted to advanced therapies medicinal products (ATMPs) based on epithelial stem cells. The successful, three-way collaboration led to the development and registration of Holoclar, the very first regenerative medicine product used in stem cell deficiency (LSCD). Holoclar received market authorization in 2015, becoming the first such drug available on the market. In 2020, Holostem recalled the marketing rights of Holoclar from Chiesi in order to assume a more complete service, which involves direct contact with clinical centres and physicians.
Background image courtesy of Depositphotos, angellodeco
“The pandemic has brought tremendous opportunities to the life sciences, first of all by bringing down walls, be they geographical or domain-based. It has become very common to create transversal teams with chemical scientists working side by side with computer scientists, but also to look for human expertise across borders.”
Fabio Bianco, CSO, Bio4Dreams
In the med-tech space, Newronika was also born as a university spin-off, this time from the University of Milan in collaboration with the Hospital Maggiore in Milan. Newronika came up with an implantable brain system that can read brain activity in order to correctly adjust neurostimulation. The process is a therapeutic procedure known as Deep Brain Stimulation (DBS) used to treat movement disorders such as Parkinson’s Disease. Newronika’s innovation to the approach is an adaptation of the closed-loop pacemaker applied to DBS. “We developed the decoding of the brain signals to understand whether a patient is responding well or if we need to adjust the stimulation. We record the signals after the implantation of the electrode after just a few days, and only then do we implant the IPG (implantable pulse generator),” said Lorenzo Rossi, CEO. Both Holostem and Newronika are exceptions in the market because these companies are taking their products to final development on their own, rather than letting the later-stage development to third parties. More common is to see Italian drug developers operating B2B models, selling an early-stage development project to a pharma company that will take it through final development and eventual commercialization. Nerviano Medical Sciences (NMS) Group, a small molecule developer focused on oncological kinase inhibitors, is looking to change this approach, revisiting both its early and late pipeline strategy after finding itself in a better cash position since being acquired by Chinese company Hafei SARI in 2017. “The acquisition and newly injected financial resources allowed NMS to change its previous business model from that of early out-licensing of products to embarking much more comprehensively in the independent clinical development of our pipeline. We are shifting the business model to carry the project later in the development phase through to PLC (proof of concept) or Phase 2 clinical trial, at which stage we can look for a global pharma partner,” said the Group’s CEO, Nanding Zhao. Other drug developers keep all options on the table. “With more investment, we could bring our product to proof of concept in the clinic; the second option is to immediately partner with a pharma company. There appears to be interest from both investors and licensing partners, and we invite those who are seriously interested to join us,” said Franco Lori, the CEO of Virostatics. Virostatics’ best-candidate for a new class of inhibitors used in the treatment of aggressive cancers is currently in advanced pre-clinical development.
Image courtesy of Cambrex
The localization of clinical trials
Whereas at the European level, the number of clinical trials has been in decline, Italy is seeing an increase in the percentage of trials conducted in the country. AIFA’s 19th National Report on Clinical Trials showed that 22% of all European trials take place in Italy. As in previous years, half of these trials are focused on oncology, but there is also a notable increase in the number of rare disease trials. 31.5% of all orphan drugs European trials are run in Italy. Even though pharma companies do not need to run a clinical trial in Italy to register their products in the country, running at least part of the product development locally may place the marketing authorization holder (MAH) in a better position during the price negotiation procedure for reimbursed drugs. Laura Crippa, the CEO of Rareg, a company offering market access and regulatory affairs services to pharma companies in rare diseases and oncology, recommends drug developers to include Italy in their clinical trials: “Italy does not only offer state-of-the-art research with highly qualified clinicians who can help with patient enrolment and treatment up to the strictest of protocols, but it is also a large market with a public healthcare system ensuring the best possible care for all patients.” Italy has made great progress in streamlining its bureaucracy and protocols. The country used to have hundreds of local and regional ethics committees, which it narrowed down and centralized under a new Centre for the coordination of Italian regional ethics committees back in 2018. Nevertheless, there are still many duplications in fees that make Italy an expensive destination for activation costs in clinical trials. Local consultancies have proven pivotal in helping smaller players navigate the regulatory field. For instance, Milan-based consultancy Del Corno & Associati works with about 120 clients, mostly SMEs but also some start-ups, who are becoming more eager to, and reliant on, outsourcing their regulatory affairs: “Italy is very particular in terms of project development, regulatory rules and the strategy needed to enter the market, so it is essential to know the market extremely well. For many years, Italian SMEs have preferred to dedicate a specific area for regulatory affairs and pharmacovigilance within the company. However, this mentality is changing in many cases and there are numerous businesses that are outsourcing these services,” said Cristina Del Corno, managing director. During the pandemic, clinical trials became even more challenging. During lockdown, all clinical trial enrolment was stopped except for oncological. During this time, CROs, who were the first affected, looked to digital and remote vists, but GDPR (General Data Protection Regulation) guidelines did not permit data transfers. UK-based CRO Pharm-Olam liaised at the European Commission to relax these data privacy measures but some sites still didn’t approve sensitive data exchanges for another 12 months. Today, the remote visit process remains a back-up option, and CROs remain hesitant. “More companies offer home-services for patients, but it is yet to see how the market will react, depending on each country. The idea is to offer greater comfort to the patient, but also minimize data entry mistakes and improve reporting. However, while the world is becoming more digital, some patients are not as digitally-savvy,” said Anna Formosa, country manager for Italy at Pharm-Olam. Opis Research, a CRO with Italian origins but operating globally, has experimented with digital monitoring, but found it not viable when used on an exclusive basis. “The quality and experience entailed by e-monitoring remain incomparable to site, unmediated observation,” said Giovanni Trolese, VP and executive director: “There is still more to explore on how to achieve better organization for the running of clinical trials during a time of crisis – and digitalization is only a part of that. Authorities should provide access to sites and support CROs to shorten training times for CRAs, for instance, as well as lending more support to submission processes.”