Viral vector technologies are at the heart of many promising new therapies, such as vaccines, gene therapies, immune-oncology therapies and other advanced therapy medicinal products (ATMPs). In this rapidly evolving and competitive landscape, there is little scope for error or inefficiency in the development process.

A contract manufacturing and development organization (CDMO) specializing in viral vector products can be a lifeline for process development and CMC managers, who bear the lion’s share of responsibility for ensuring their company’s innovations make it from bench to bench clinic as quickly and efficiently as possible. Outsourcing to a CDMO is one of the best ways to de-risk and accelerate viral vector projects—provided it is carefully planned and managed. So how do you engage effectively with a CDMO and make the most of this vital relationship? Here are 5 steps to a successful collaboration.

1. Start early

In viral vector product development, the seeds of success—or failure—are sown early. In particular, there are many challenges and pitfalls when taking a product from proof-of-concept to the first clinical trials. The decisions you make at this stage can have major consequences regarding the overall capability, reliability, quality and cost-efficiency of your process.

By reaching out to a CDMO in the early stages of development, you can benefit from the full range of their experience, capabilities and services. This usually starts with a comprehensive evaluation. For example, how scalable is your current process? Is your cell line suitable for GMP manufacturing? Do you have the appropriate analytical methods for in-process and release testing?

A CDMO with a strong track record in viral vector development and process engineering should be able to evaluate your project from every angle—scientific, technical, operational, cost and regulatory. An early assessment will maximize the number of design options available and ensure that strategic gaps, issues, and potential stumbling blocks are spotted early, before they become problematic.

2. Be clear about what you need and want from a CDMO

The first step to getting what you want from a CDMO partnership is knowing what you want. This may sound trivial, but it is surprising how often companies reach out to a CDMO with a request for proposal (RFP) before having a clear idea about precisely what they need to get out of the partnership and how they prefer to collaborate.

Before engaging with a CDMO, it is a good idea to run a gap analysis to assess your in-house capabilities and identify any gaps you think need filling regarding skills, expertise and resources. Consider also the more intangible qualities that make for a good working relationship. Intangible qualities could be your preferred communication style, the importance of compatible values, and the degree of responsiveness, flexibility and support you expect from a potential partner.

3. Find the right fit

With your general needs and preferences in mind, you will be better positioned to research potential CDMOs, articulate your needs, and effectively interview candidates. At the same time, it is vital to remain open-minded in your initial discussions with CDMOs. In many cases, they will be able to spot gaps or needs that weren’t identified in your gap analysis.

Some of the key topics to explore with potential CDMOs include:

• Range of services and competencies. Does the CDMO have the right capabilities to cover all of your needs, from virus and cell banking to regulatory sign-off and support for manufacturing handover?
• Track record in viral vector process development and clinical manufacturing. How extensive is the range of viral vectors they have successfully manufactured? Will your vector system be new to them?
• Flexibility to tailor their approach and processes to meet your vector-specific requirements.
• Equipment and facilities. Are they appropriate for your current and future needs?
• Regulatory history and experience with IND/IMPD dossier submissions. Can the CDMO prepare and provide all the necessary information for filing? Do they offer support in completing the CMC section?
• Project and program management capabilities. How experienced are they at managing complex viral vector development projects? Would you be able to trust them to drive your project forward while you focus on the high-level strategy and manage your in-house team?
• Capacity and willingness to support you at every stage of the project. Importantly, how will the CDMO prioritize your project against existing work or the needs of larger clients?

Before you make your final selection, arrange some face-to-face time with the leadership team. If possible, an on-site meeting will help you assess the culture. During such a meeting you can get a sense of what it would be like to work together. Do they listen? Are they open and easy to get along with? Do you feel comfortable working together? Is this a company you can trust to deliver?

4. Align and organize

Once you have found a good match, proactive engagement is key to ensuring your project gets off to a good start. This includes putting the right mechanisms in place to keep the momentum going. Together with the CDMO, organize an on-site kick-off meeting to align on project vision and scope. Key milestones, priorities and ways of working can be established during the meeting. Ensure roles and responsibilities are clearly defined from the start so there is ownership when problems arise. Along the way, note how quickly the CDMO gets up to speed and takes action on your requests. If they are slow to respond in the signing of documents, for example, or to address your questions and concerns, this could be an early warning sign.

5. Maintain strong lines of communication

Lastly, never underestimate the importance of transparency and regular communication throughout your project. Establishing a schedule of communication and sticking to it will help you build strong connections and establish trust. Your CDMO should also be willing and available to participate in more impromptu discussions to work out any issues as soon as they arise. The more proactive you are about ensuring the lines of communication are open, the better able you will be to build a productive and lasting partnership.

Partnering with a CDMO can make a world of difference for your project. To discover how, talk to one of our experts. They will be happy to discuss your needs and perform a free review of your current process.

Without doubt, biotech startups and smaller pharmaceutical companies have become the major drivers of innovation in the pharmaceutical industry. In 2020, 63% of approved new therapeutic drugs in Europe and the US came from small-to-medium enterprises. Yet for every success, there are countless tales of defeat. How do investors and executive managers bridge the gap between identifying a promising drug candidate and turning out a commercially successful product? While there is no simple answer to this question, one thing is certain: behind every successful new drug, there is a well-crafted product development plan (PDP). In this article, we explore why and how to use this pivotal tool to formulate a winning drug development strategy.

The PDP: where opportunity meets reality

Bringing a beneficial new drug or therapy to patients is an exciting opportunity and a worthy goal, but not without significant risks. For the best chance of success, it is imperative to start out with a realistic understanding of what lies ahead, and a solid plan of how to arrive at an end product that is not only marketable but will give a healthy return on investment.

Even with sound science and technology as the starting point, turning a lead candidate into a commercially viable drug is no easy feat. It is a multidisciplinary effort that requires extensive planning and coordination, as well as a clear vision of the end goal.

As we saw previously, partnering with more experienced industry players who have been there before and know what to expect is one way that smaller biotech companies can improve their chances of success. Another is to make sure there is a sound product development plan (PDP) in place from the start.

What is a PDP?

The PDP is a strategic document that creates a detailed and comprehensive picture of the development strategy. It serves as a step-by-step guide to arrive at the envisioned drug product. For each stage of the development process, the PDP clarifies the major goals and critical success factors, specifying how success will be measured and what needs to be done to mitigate any risks.

A well-designed PDP not only increases the chances of success, it also plays an important role in helping the program teams reduce cost of goods, maximize efficiency and shorten time to market.

The news no CEO wants to hear

Imagine having spent several years and several million investor dollars to get a drug candidate successfully through phase 1 clinical trials, only to learn that your manufacturing process is not suitable for commercial scale production or that the COGS is too high.

Or perhaps your new gene therapy turns out to be the next Zolgensma, with a price tag of over $2M per patient. Will the benefit to patients justify the price of your product? Will insurers agree to cover it? If not, it may mean going back to the drawing board to rework the formulation or the manufacturing process.

What if you had to tell stakeholders that there would be a massive delay in bringing your product to the market because you did not correctly anticipate pivotal next steps and investments?

All of these scenarios are catastrophic for any company, but in particular for smaller companies that pursue a product strategy rather than a technology platform strategy.

For companies relying on Big Pharma partnerships, Menzo Havenga, President & CEO of Batavia Biosciences offers these additional words of caution:

“If at the heart of your company strategy a big pharma partner is imperative, then please note that they will take a meticulous look at the manufacturing process underlying your Phase I clinical data. Should there be any risk that the process cannot be scaled to final commercial volume, they may find the return on investment disappointing.”

Scenarios like this happen far more often than you might think, especially when developing complex biological products or advanced therapeutics, where there may be no established manufacturing or commercialization paradigms, and the path to regulatory approval is uncertain.

Where does it all go wrong? More often than not, the cause of costly delays and roadblocks can be traced back to inadequate planning or failure to fully appreciate the commercial aspects of the program and their implications in product development.

What is the role of the PDP and who will use it?

Given that a typical drug can take over a decade and more than $2 billion to develop, business leaders need to be fully aware upfront, before spending money, of what they’re getting themselves, their teams and their stakeholders into. The PDP lays everything out on the table from the start, so that the chance of success can be accurately assessed. This starts with being brutally honest about capabilities, weaknesses and deficits, as well as any challenges and risks they face.

As the program unfolds, executive management, potential partners and investors need to be presented with all the relevant facts and information required to decide whether the investment is a viable one, and whether all the criteria have been met to progress to the next stage gate.

In addition, teams executing on the plan will need to have clear guidance on strategy and know what steps to take at every stage of the development process in order to gather the right information and achieve the end goals. They will need to follow the metrics to success, understand what contingency plans are in place, and know when to act on them should things go wrong. A good PDP helps ensure timely action so that there is a smooth transition between phases. In particular, it helps your teams understand how any proposed changes will impact the program as a whole, so that they can make mission-critical decisions without delay.

On this point, Christopher Yallop, COO of Batavia Biosciences comments:

“As any cyclist knows, if you are on your bike and looking only at the tarmac you will not see the bus coming around the corner! It’s imperative when developing a drug that you see the road ahead and steer when needed. That’s where the PDP is essential.”

Finally, Program leaders must of course have sight of the big picture to be able to delegate responsibilities and coordinate the activities of all the relevant teams—including finance, marketing, non-clinical and clinical development, quality assurance, and regulatory affairs. They can refer to the plan to check whether teams are on track to meet important milestones and deliver to specification and within budget.

The PDP is the central command station that makes all of this possible.

What are the benefits of creating a Product Development Plan for your drug candidate?

1. Provides clear guidance at each stage
2. Serves as a reality check
3. Facilitates communication
4. Improves alignment
5. Drives agility and sound decision-making
6. Increases efficiency

What should be in the product development plan?

In practice, the PDP is not one strategy, but many. The key to creating a well-integrated program is to ensure that the PDP encompasses all stages and aspects of the drug development program. While the structure and content may vary, most drug development plans include these components:

Executive summary – gives a high-level overview of the drug product and target patient, the market position, as well as a summary of the financial figures and projections needed to support investment and stage gate decisions.

Marketing strategy and business case – focuses in more detail on the commercial aspects of the program, plotting the strategy for achieving the necessary market penetration and expected return on investment
Intellectual property and trademark strategy – plays a crucial role in maintaining competitive advantage, ensuring protection in major markets, and responding quickly to any changes in the IP landscape

Target Product Profile (TPP) – often described as the backbone of the PDP, the TPP details the target product attributes needed to obtain regulatory approval and to satisfy commercial goals; these specifications are crucial in determining what can be claimed on the product label, and they also drive the design and evidence gathering strategies for other critical program elements.

Detailed roadmaps – comprise the ‘meat and bones’ of the PDP, laying out the most effective strategies for non-clinical and clinical development, CMC, manufacturing, regulatory affairs, and quality assurance.
Project organization, planning and budget considerations

How to get it right the first time

Having a PDP in place as early as possible lays a solid foundation for success, but only if it has the right structure and content. To see what a typical PDP looks like, request our free PDP template, which you can access after completing the form below. In the next and final article of this series, we’ll discuss how to put together the most effective PDP for your drug development program.

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Viral vector technologies are taking center stage in the development of novel vaccines and therapies to combat a wide spectrum of human diseases. Efficient development of safe, cost-effective, and robust methods for viral vector manufacture is therefore of vital importance for patients to benefit from these potentially life changing new medicines.

Can I use my cell line for clinical production? What is the quickest route to clinical trials? How can we effectively de-risk and accelerate viral vector development? These are just a few of the many questions we address in this go-to resource for anyone navigating the complexities of viral vector process development, scale-up, and cGMP manufacturing.

Viral vector technologies

The use of viral vectors in vaccines and targeted therapies is revolutionizing the way we tackle some of nature’s most intractable human diseases and infectious pathogens. From rare diseases to cancer to COVID-19: viral vectors are becoming indispensible weapons in the armory of drug modalities?

What are viral vectors

Viral vectors are viruses that have been engineered in the lab to efficiently infect target cells and deliver a genetic payload. These properties make them highly attractive for a wide variety of clinical applications.

When genetically engineered with the code for an immunogenic antigen, viral vectors essentially hijack the cell’s own machinery to produce large amounts of the antigen, which is then effectively presented to the host immune system. This makes them an attractive platform for development of novel prophylactic and therapeutic viral vector vaccines.

Viral vectors also offer tremendous promise for the development of novel cell and gene therapies. An estimated 70% of gene therapy trials worldwide involve the use of viral vectors.

The scope of viral vector technology further extends to the development of oncolytic viruses, a rapidly evolving class of anticancer agents that are tailored to specifically target cancer cells for destruction, working in combination with the patient’s immune system.

Viral vector vaccines 

The rising global threat of infectious diseases and cancers has been a major driver in the evolution of next-generation vaccines.

Milestones in preventative and therapeutic viral vector vaccines

Viral vector technologies in particular have emerged as an enabling platform for vaccine development. Notably, the technology gave rise to the first FDA-approved vaccine for Ebola virus in late 2019, and in December 2020 the first viral vector vaccines for SARS-CoV-2 / COVID-19 were granted emergency use authorization (EUA) less than a year after the genetic sequence for SARS-CoV-2 was shared.

Milestones like these, underpinned by significant progress in addressing safety and scale-up challenges over the past few years, are paving the way to more widespread adoption of viral vectors in vaccine development.

Table 1. Human clinical trials in progress with viral vectored vaccines^1,2

Biotechnology is in the midst of a great era of innovation, with an ever-expanding toolbox of drug modalities spawning development of exciting new vaccines, medicines and therapies. Today’s ecosystem for innovation in drug development looks quite different compared to ten or twenty years ago, with many more symbiotic relationships between venture capital (VC)-backed pharma and small biotech startups working to diffuse risk across the development lifecycle.

On the upside, the appetite for investment in the life science industry is big and getting bigger.  According to Silicon Valley Bank’s 2020 annual report, biopharma investment hit record highs for the fourth straight year in a row, in terms of both the number of deals and the dollars invested.  Especially encouraging for biotech startups was the significant increase in Series A funding in 2020 compared to 2019.  Into 2021 the venture capital outlook continues to look bright, with PitchBook predicting that this year “Biotech and pharma VC deal activity will likely exceed $20B for the second consecutive year.”

Big fish, little fish – finding a niche in the funding ecosystem

On a more sobering note, even as VC-backed innovation flourishes, the competition for early stage funding among biotech companies is fierce, with much of the investment dollars going into the hands of fewer but more well-connected players—the big fish, if you will.

“What we’ve really seen lagging now is seed money for new founders who don’t have a track record for having started successful companies in the past and don’t have a very strong extensive network of people in funding and in company development,” says Craig Kaneski, an associate in patents and innovations at the law firm Wilson Sonsini. Speaking in a September 2020 webinar on navigating the life science funding landscape, Kaneski elaborated: “We’ve observed that some deals are deemed more for founders that are very experienced and have strong track records, [including] a good track record with VCs.”

So the big question is – what about those little fish – the biotech startups who have great ideas, but whose founders haven’t been lucky enough, or in the game long enough, to have the same track record and connections as the big players?  How do they find their niche in the ecosystem?

Big Pharma as a resource for biotech startups

A common perception is that funding and support from a large pharmaceutical company only becomes relevant for biotech startups when their product is in the latter stages of development—that is to say, after the development project has been significantly ‘de-risked’ by the startup company.  But a recent analysis of how large pharma impacts biotechnology startup success turns this thinking on its head.

In their study published in Nature Biotechnology, analysts from two venture capital firms in the Netherlands trawled GlobalData’s Pharma database to identify all deals between large pharma and biotechnology startups over the 15-year period from 2004-2019. They then looked to see whether there was a link between startup success rate and having an established connection with a pharmaceutical company.  In this case, they defined success as being listed on public markets (IPO), acquired (majority or 100%), or having had a drug approved during the period in question.

Remarkably, they found that the startup success rate increased from 18% to 37% when a large pharma investor was on board. This connection also increased both the size of success (from a median of $138M to $332M market capitalization) and the acquisition value (from $136M to $377M).  Counter to the prevailing dogma, they found that success rates were boosted for startups that partnered not just at the clinical stage, but also earlier—during preclinical development. They concluded that large pharma partnerships are advantageous throughout the startup lifecycle—from the preclinical stage through exit by acquisition or IPO.

What are the reasons for this positive effect?  In the early stages of development, the authors suggest that access to the pharma partner’s intellectual property (IP) may play a significant role.  They speculate that the pharma partner essentially de-risks the IP before outlicensing it to the startup, which could effectively give them an edge over competitors.

They also highlight what is perhaps an even more important factor: that a large pharma partner can provide ongoing support—in terms of both resources and specific expertise that entrepreneurs may be lacking—for example, in GMP clinical development, regulatory interactions and large-scale manufacturing.

Partnering to build credibility

Another expert panelist in the life science funding landscape webinar we mentioned earlier, Cynthia (Cyndi) Green, commented on how difficult it can be for startups to succeed in the competitive biopharmaceutical space:

“On the therapeutic side of things, which is really where I’ve spent most of my time, therapeutics and vaccines, it’s tough,” says Green.  “We’re looking to invest in early stage, and when something doesn’t have clinical data yet—and a lot of times definitely doesn’t have efficacy data—it’s a hard sell and it’s a lot of risk.”

As Managing Director of Connecticut Innovations, the state’s strategic venture capital arm, Green has had a wealth of experience supporting the growth of innovative biotech companies. From what she’s seen, surviving in this competitive landscape has a lot to do with giving potential partners and investors confidence that you know what you’re doing.  She highlights the importance of having access to specialized expertise—either in-house or through partnerships—in any areas that are unfamiliar:

“If you are a new entrepreneur, try to get somebody on your team, at least as an advisor, that’s ‘been there done that’ and has credibility…[Investors] have to have faith in the [startup’s] team and their ability to find the correct advisors, to take help, and to do well with your money.”

The rise of Center of Excellence CDMOs

By definition, being an innovative biotech startup means breaking new ground. Working with a new drug modality—for example, a novel type of viral vector—may call for completely new development and manufacturing strategies.  This frequently requires entrepreneurs to venture into unfamiliar territory, especially in areas such as production scale-up, regulatory compliance and cost-of-goods estimation.

In such cases, a specialized contract development and manufacturing organization (CDMO) is another valuable resource that can give new startups an edge.  With years of experience and expertise in scale-up and manufacture of complex biological products, a CDMO can help teams avoid common pitfalls and find the quickest route to the next development milestone.

In particular, there’s a new breed of CDMO emerging, called a Center of Excellence CDMO (CoE CDMO). CoE CDMOs go beyond service provision. They provide leadership in their particular areas of focus, share best practices, and are able to offer more tailored solutions. Importantly, they aim to create long-term partnerships with their customers, which means they can often provide more comprehensive support and guidance across the development cycle.

If Green is right, having a CoE-CDMO on your side may be just the sort of knowledgeable expert you need to boost credibility with potential VC and pharma investors, and get your innovative product into the clinic sooner.

Looking for more insights on this topic? Don’t miss our next article, where we take a closer look at the elements of a successful Product Development Plan and how you can use one to build credibility with potential investors and partners.