Five Strategies For a Thriving Pipeline

Building a new therapeutic portfolio is a highly risky and resource-intensive proposition. This is particularly true for small- to mid-size companies without an established commercial portfolio. While the biopharma industry has not yet invented a crystal ball to guide our R&D decisions, there are several key factors that can dramatically de-risk this endeavor and increase the likelihood of pipeline growth.

Six years ago, Zai Lab began building a pipeline of investigational compounds that now align under what we call our neuroscience, autoimmune and infectious disease (NSAiID) portfolio. Over the past six years, we’ve brought five products into this portfolio, each of which has either generated a first regulatory approval or appears on track to do so within the next several years. This “five-for-five” strategy validates Zai’s approach to drug discovery, in-licensing and drug development.

Five Strategies That Fuel “Five-For-Five”

• Focus on What You Know: As an infectious disease (ID) specialist by training with significant ID and immunology drug development experience, I initially joined Zai Lab to help the company evaluate an in-licensing opportunity for the novel antibacterial omadacycline (NUZYRA). This became the first product in our NSAiID portfolio and is currently marketed in both the United States and Chinese mainland. It set the tone for our approach going forward: We focus on mechanistic and therapeutic areas where our team members already have in-depth scientific and practical expertise. We’re not going to chase the next emerging therapeutic area or drug class just because it seems promising. We are opportunistic, but we stick with what we know.
• Understand the Biology: As we explore new areas and assets, our team’s first and foremost goal is to identify opportunities where there is an in-depth understanding of the respective disease’s pathogenesis and the corresponding compound’s mechanism of action (MOA). There must be a reasonably well-understood pathogenicity and then within that degree of certainty, we look for innovative approaches to impact this biology. In-depth understanding of disease biology has had the added benefit of revealing synergies and new opportunities within the NSAiID therapeutic areas.
• Lean Into De-Risked Assets: At Zai, we’re not risk averse, but neither are we interested in moon shots. Within our areas of focus that meet the criteria outlined above, we also look intensively at de-risked assets. Our current interleukin-17 (IL-17) program exemplifies this approach. Interleukins are extensively studied compounds that have been applied to multiple disease areas. There are currently three FDA-approved, injectable IL-17 inhibitors to treat plaque psoriasis and psoriatic arthritis. Six years ago, our team looked at this well-understood mechanism and identified a significant opportunity to improve patient care. Today, we are the only company with a topical IL-17 treatment in development.
• Prioritize Differentiation: Within this balancing act of innovation and risk, we also mine for clearly differentiated MOA and formulation approaches. This commitment has helped us prioritize compounds with high potential to deliver meaningful patient benefit. KarXT, which we are exploring in partnership with Karuna Therapeutics, is an ideal example of this strategy. Unlike typical antipsychotic medications, which rely on the dopaminergic or serotonergic pathway to treat symptoms of mental illness and are often associated with debilitating side effects, KarXT is a muscarinic agonist. We saw significant potential in this new and unique mechanism of action to beneficially impact the lives of millions of people with serious mental illness.
• Partner Strategically: Partnering to co-create, develop and market new medications can substantially reduce development risk and exponentially increase the probability of pipeline growth. Zai was founded to be a partner of choice – first in China where we have an unsurpassed understanding of the clinical trial, regulatory and marketing landscapes, and eventually globally. Partnering with argenx on efgartigimod (VYVGART), we contributed 20 percent of clinical trial participants for a key indication and even re-opened trial sites when needed to help meet global enrollment timelines. Leveraging our respective capabilities and expertise, the Zai Lab/argenx partnership is on track to reach thousands of patients in diverse markets globally with a differentiated therapy.

As a practicing clinician and long-term drug developer, I’ve been part of many approaches to therapeutic discovery and development. After 25 years of experience in the biopharma industry, I know this to be true: While risk is inextricable from this undertaking, it can be minimized substantially as we move toward the reward of providing effective new therapies to patients in need.