An Enduring Drug Discovery Partnership Built on Complimentary Qualities

Enduring partnerships take effort; they take strong communication and a vision for a future that will outlast even the participants. While match-making sites obsess over finding commonalities, often the best partnerships are built on complementary qualities and skillsets. Take Kyowa Kirin, Inc. and La Jolla Institute for Immunology (LJI), for example. 

The New Jersey-based specialty company and La Jolla, California-headquartered research institute have been scientific collaborators for more than 30 years. The partnership has worked so well, the two recently signed up for another three years. They’re not commitment-phobes - clearly - the three-year increments just give them the opportunity to take a pause and reassess their priorities.

The current COVID-19 pandemic has illustrated the importance of private-public partnerships. COVID-19 therapeutic molnupiravir is the fruit borne of collaboration between Emory University, Ridgeback Biotherapeutics and finally Merck & Co. While the latter stands in the spotlight, the drug would never have come to be were it not for the efforts of the other two. 

Andrew McKnight, Chief Research Officer and head of open innovation at Kyowa Kirin North America (KKNA), also spoke to the significant value of these alliances.   

“A lot of the really novel, early research ideas, I feel come out of academic research, but a lot of academic institutes kind of struggle to take those discoveries to the next phase,” McKnight told BioSpace. LJI scientists may, for example, identify new biological pathways. Then KKNA, with its drug development expertise, can either help LJI advance those discoveries or license them outright and take them into the end zone.

It also provides the opportunity for LJI faculty and postdocs to make a more immediate impact on drug development while offering a different perspective to KKNA.

“I think it's important to highlight that these guys have stepped up to the plate and they are funding the work of some young investigators, postdocs and even graduate students who come up with clever ideas for research,” said Joel Martin, Ph.D., managing director and Chief Business Officer at LJI. “They may go into academic positions, even at our own institute, or they may go into industry, so this really gives them a leg up that might not otherwise be available.” 

“It gives us access to the 21 faculty members and the expertise they have in their respective fields,” McKnight added.

Also key to any good relationship is the ability to share a common living (or working) space. While LJI dominates this pair’s shared research space with its nearly 500 staff compared with KKNA’s 45, the arrangement has a lot of practical advantages.

“Science runs on technology now, more and more heavily every year,” Martin said. “We share a lot of facilities and core technologies that might not otherwise be available, and then [KKNA] contributes in kind with both their expertise and financing.” 

Before looking at the alliance’s current focuses, let’s begin with a bit of history. Back in the 1980s, Japan-based Kirin Pharmaceuticals took a deep dive into biotechnology, establishing Gemini Science (now Kyowa Kirin Research, La Jolla) in San Diego to support a new partnership with Amgen. Looking to learn more about the emerging sector, Gemini partially funded the launch of LJI in 1989. The alliance was literally born with big shoes to fill. LJI’s inaugural scientific director was a Japanese immunologist by the name of Kimishige "Kimi" Ishizaka who, along with his wife, Teruko Ishizaka, discovered the antibody class Immunoglobulin (IgE) in 1966. This was considered a significant breakthrough in understanding how allergies worked.

Throughout the years, LJI and KKNA have honored these auspicious beginnings.

Together, they brainstormed an antibody against CD40, a key molecule for the upregulation of HIF-1alpha and PTEN. KKNA took this antibody into Phase II clinical development, partnered with Astellas, as a potential solution to repress kidney transplant rejection. The partners also developed an antibody against a molecule called LIGHT, a member of the TNF superfamily. Avalo Therapeutics licensed that antibody and is now developing it in the clinic for a rare form of Crohn’s disease and Acute Respiratory Distress Syndrome (ARDS).

McKnight’s favorite example, though, is the development of KHK4083, an anti-OX40 fully human monoclonal antibody which KKNA is jointly developing and commercializing with Amgen for the treatment of atopic dermatitis. He shared that a lot of the early, pre-discovery work around the OX40 molecule was done in collaboration with LJI.

“Interestingly,” he said, “all three of them are antibodies – biologics – which speaks to the strength of the immunology expertise we have between both organizations.”

Every three years, the two parties sit down at the table and discuss how LJI’s cutting-edge science could best fit with KKNA’s commercial interests. Not all academic research is at the right stage for commercial opportunities. While McKnight shared that KKNA primarily looks to fund projects in its core therapeutic focus areas of inflammatory disease, autoimmunity, oncology and CNS, the company does sponsor other endeavors in infectious disease in the interest of supporting public health initiatives.

They also step back and assess the current state of immunology. On this, both men had some very definite thoughts.

“Immunology touches on everything, every aspect of your body's function, from neuroscience to cancer, you name it,” Martin said. For him, key areas of focus include the often-ignored neuroimmunology space, the microbiome and its interaction with the gut, and virology. Martin also highlighted a new LJI initiative which looks at gender-based responses to disease, an area he said is “largely ignored.”

He added that LJI is building a discovery center for antibodies and vaccines, and working closely with KKNA on antibody discovery technology.

McKnight also had a tough time narrowing it down to just a few.

“The immune system is incredibly complex,” he said. “I think some people often forget that the immune system is there to protect us from infectious disease, but when it goes wrong, it leads to inflammatory and autoimmune disease.”

So, one key area is harnessing the potential of regulatory T cells, which normally suppress autoimmune diseases, in specific tissues. McKnight also highlighted bi-specific antibodies.

“A lot of the antibodies that are on the market today, TNF, interleukin 12 or interleukin 23, they all bind to a specific molecule,” he said. Kyowa Kirin, along with a number of other companies are developing bi-specific and even tri-specific antibodies. By binding two or more targets at once, “you could actually bind a target molecule in a specific tissue and not bind a target molecule in other tissues.” 

Finally, McKnight said, there is still a considerable unmet need in fibrotic diseases such as pulmonary fibrosis and Non-Alcoholic Steatohepatitis (NASH). This is a hot target being chased by countless large pharma companies and small biopharmas alike. 

Ultimately, McKnight shared his hopes that another potential blockbuster would emerge from the partnership.

“I think we’d both love to see another high profile target that Kyowa Kirin could apply their technologies to in drug discovery, and come up with another clinical candidate, or two or three,” he said, adding that he recently reviewed several new proposals from LJI faculty and junior investigators. “My hope would be that some of those early seeds would lead to drug discovery targets for the future.”