Antibody-drug Conjugates or ADCs are among the most exciting drug developments of the last decade. The combination of potent, small molecule drugs with the highly target specificity of monoclonal antibodies allows sensitive discrimination between healthy and diseased tissue. This approach has demonstrated great efficacy – and safety – in the fight against cancer and hematological malignancies.  Antibody-drug Conjugates are part of a specialized subset of highly potent active pharmaceutical ingredients (APIs).

Today, the development of this technically challenging new class of highly potent biopharmaceutical drugs is rapidly expanding. On average, each month more than one new ADC is entering a clinical trial.  This progress, as well as the increased development of innovative payloads, novel linkers chemistry and new site-specific conjugation technologies, is creating much excitement among scientists and researchers involved in the development of these specialized, personalized and targeted therapeutics.  But, looking ahead, the excitement among researchers and scientists is especially good news for patients  and their physicians who are trying to help find solutions for, so far, unmet medical needs.

This interview is the first in a series with experts involved in the research, development and manufacturing  of Antibody-drug Conjugates. We will be talking to individual scientists and researchers involved in the development process as well as key employees of pharmaceutical companies, contract (development) manufacturing organizations and physicians involved in clinical trials with ADCs.

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Earlier this year we interviewed Lonza’s Laurent Ducry, PhD, who, since 2008, is leading the antibody-drug conjugates R&D group of Lonza (Visp, Switzerland).  Ducry is editor of “Antibody-Drug Conjugates: Methods and Protocols” (Springer, Humana Press, 2013) and a member of the Editorial Advisory Board of ADC Review / Journal of Antibody-drug Conjugates.

In this interview we discussed a variety of subjects related to the development of ADCs, how market conditions and the industry are changing, the impact of personalized and targeted therapies as well as expectations of approved drugs, drugs in the growing pipeline of novel ADC and how this is impacting medicine.

Projections
ADC Review (Question): The ADC market is a growing market. What is your expectation for the ADC market in the next 5-10 years? In particular, with 2 currently approved drugs, and more than 40+ in clinical trials (a number that is growing every month), what do projections look like?

Laurent Ducry (Answer): We expect to see significant growth in what we call targeted drugs and bioconjugates/ADCs are certainly within that category. At ASCO this year, we did see some very promising data from ADCs in the clinical pipeline and we definitely expect to see them in the cancer therapy toolbox in the next 5-10 years. Also, the pipeline is expected to grow considerably, which is evidenced by the significant activity we see in both in-house research and licensing activities.

Changing medicine
Question: How is the development of ADCs, and other targeted therapies, such as CAR-T, PD-L1s and nanodrugs, changing medicine? What does this means for the industry?  How does this impact the need for specialized companies like Lonza?

Answer: This is an exciting time for our company. We are the leading CMO in the world with substantial experience in manufacturing targeted therapeutics technologies and bringing them to the market. Cell and viral therapies, monoclonal antibodies, and bioconjugates all fall under our areas of expertise. Companies like ours that are already well positioned to provide development and manufacturing services for these therapies will benefit from these trends.

We are seeing incredible responses to some of the products utilizing these technologies and the markets are responding accordingly. It is truly a remarkable time to be part of this process.

Personalized and targeted therapies
Question: Based on the previous question. In therapeutic areas like oncology and hematology, there is a drive towards personalization/individualization of therapies.  How does this change medicine?  What role, if any, does Lonza play – and, how may this change the role of CDMOs in general. What can Lonza offer to help their (pharmaceutical) clients to be successful in this unique market?

Answer: That is correct, as I mentioned before, targeted/personalized therapies will become the norm especially in indications like oncology and rare diseases. From a manufacturing perspective, each therapy will bring its own challenges but commitment to quality, peace of mind and product launch experience is something Lonza can uniquely offer in this changing landscape.

Impact of novel payloads and improved linker chemistry
Question: Ongoing research points to new developments in ADCs (different linkers, payloads and monoclonal antibodies. How does Lonza expect this to impact the market? And, how does Lonza’s experience benefit industry players.  How is this different from other industry players?

Answer: I think we will start to see more and more of these newer generation products hitting later phases and every new wave should bring differentiating advantages. From a development perspective, you need teams that have enough experience to handle these complex and new technologies. As a leader in the ADC business, we can safely say our research and development teams have seen and have had experience with almost all of the novel technologies and methods we see coming down the pipe. We know not many CMOs can say that confidently.

Shaping the future
Question: How does Lonza see the future or these novel drugs and what is the role Lonza plays in shaping the future of ADC and other targeted therapies?

Answer: When we are dealing with oncology and rare diseases, what we have learned is that one size-fits-all approach can only provide marginal benefit to patients. We will need novel treatments utilizing newer technologies like cell therapy and ADCs and also we will need to employ combination treatment algorithms. Developing and manufacturing these therapies, some of which may be used concomitantly requires combining several specialized teams of scientists working together. We have these teams ready to be deployed as soon as our customers come to us.

A quantum leap
Question: How do those changes impact health policy in the United States and abroad?  How does this impact treatment and treatment “value” and, finally, how does this impact medical technology?

Answer: Targeted and combination treatments will have multiple implications from a policy and value perspective. First of all, companies need to think creatively in terms of identifying those patient groups that will benefit from these novel products and providing access to them. Also, for the first time we are seeing almost a “quantum leap” in terms of the potential benefits of these products. “Cure” is often used to describe the patient responses achieved in early clinical trials. Obviously, this brings the question of “value” and payment methods. Also, how you will manufacture, administer, get paid for these combination therapies is an additional challenge. This is where forming a strategic partnership with a powerful CDMO that can tackle the manufacturing challenges and also assist through the approval and reimbursement processes will be crucial for pharma/biotech companies.

There are only a few facilities/companies around the world capable of offering a “one-stop shop” for the development of ADCs (from monoclonal antibody development/production to linker technology, cytotoxins, fill/finish, regulatory services, etc.). How does Lonza support their clients in this important therapeutic area and how does the company help customers seamlessly scale ADC production from preclinical to commercial phases? Given the announcements and media attention to SAFCs expansion, how important is geography?  How is an U.S, based competitor facility expected to impact Lonza? What is Lonza doing to counter this?

When you look at the landscape of facilities that manufacture ADCs, we see a disparity between companies in terms of strength in different areas. Some have more mab or cytotoxin experience, some are emphasizing fill/finish capabilities, etc. In my opinion, there is only one company that has the amount of experience in every “piece-of-the-ADC-puzzle”. We have had a good number of successful biologic product launches and a strong track record with ADCs.

For some companies, geography may play a role in their decision to pick a CMO but at the end of the day, most of the customers we work with would eventually target the global market. “Would you prefer proximity over expertise?” is an important question to ask when you make a decision.

Question: Can you describe some of the developments and additional services/updates created by Lonza, and how does this set the company apart? What makes Lonza the industry leader in the ADC market? What is new, unique? What has worked and what did not?

Answer: We are investing in our development capabilities and manufacturing facilities on an ongoing basis. Because of our reputation, companies are eager to bring new technologies like different site specific conjugation methods, novel toxins, etc. to us. Therefore, we have amassed a technology know-how among our scientists that is We have seen every site-specific conjugation method, every major toxin-linker combination available in the pipeline. Our facilities are state-of-the-art. We now have single-use systems available for our customers and we constantly look for ways to improve both product efficacy, safety and manufacturing methods.

A competitive field
Question: In a recent conversation with representatives from Merck KgaA, it was made clear that Merck is expanding its offerings in targeted therapies. In 2014 Merck took over SAFCs parent company (Sigma Aldrich).  How important is this development?  How does Lonza view this?  Is there a benefit to be part of large pharmaceutical company or are there more benefits to operate independently (like Lonza is doing today)? How does Lonza feel, will this ‘merger’ change the (CDMO) industry?

Answer: It is an important development and we are watching their strategy closely. The benefit for Merck is obvious, however, we are working in a very competitive field where manufacturing details could set one product apart from another. Having that sensitive information in the hands of an independent company like Lonza vs. the subsidiary of another pharma company is something to think about. We have already heard our customers voice that reluctance.

The ultimate cancer toolbox
Question: What are some other changes (industry and market developments) that will impact the industry and market in the (near) future – 2015 – 2020 – 2025?

Answer: Nano technologies, T-cells, different payloads are all being tested and while it is hard to predict a clear winner, it is clear the pipelines will not be homogeneous and the ultimate cancer toolbox will look very different than what we have today.


Last Editorial Review: December 2, 2015

Photo: Laurent Ducry, PhD, since 2008 leading the ADC R&D group of Lonza (Visp, Switzerland) Courtesy: © Lonza. Used with permission.

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