The American Dream is why the United States is considered the “land of opportunity,” and why for centuries immigrants have flocked to our shores seeking their fortunes. Guo-Liang Yu, Ph.D., (China), and Sanjeev Redkar, Ph.D., (India), came to the U.S. in the 1980s. By anyone’s reasonable measure, both have achieved the American Dream. However, their dream as scientists remained at arm’s length. Their desire? Create a pharmaceutical company that leverages the best of what the U.S. and China have to offer toward discovering and developing new oncology therapeutics, while using the smallest drug development program possible to do so. This is the story of how the scientific careers of an intrapreneur (Redkar) and an entrepreneur (Yu) came together to cofound and co-lead Apollomics.
“The American Dream is that dream of a land in which life should be better and richer and fuller for everyone, with opportunity for each according to ability or achievement.” — James Truslow Adams
From Immigrant To Biopharma Intrapreneur
After arriving in the U.S. in 1989, Redkar completed his M.S. and Ph.D. degrees in chemical engineering and took a job as a research scientist with Matrix Pharmaceutical in the San Francisco Bay area. While those were formative years, it wasn’t until 1998 when he joined SuperGen that the scientist embarked on his intrapreneurial journey. “We had a lab where we were coming up with novel formulations for cancer drugs,” he recalls. “We formed an internal group, and I started filing and prosecuting a lot of patents.” Prosecuting in the sense that he worked closely with company lawyers to figure out what was needed to get SuperGen’s IP protected. Realizing he had much to learn, he took a week-long intensive course on patents. This helped him understand the importance of the Manual of Patent Examining Procedure (MPEP), which is the “Bible” for patent attorneys and agents. Being able to apply this skill is one reason he holds more than 200 patents today.
Redkar’s stint at SuperGen (later renamed Astex Pharmaceuticals) lasted almost 18 years. “We had a lot of commercial programs for the oncology drugs we were bringing to market, so I got to work closely with my commercial colleagues, an experience I’d advocate for all scientists.” This experience was, in part, why he went back to get an MBA in 2008. “If I wanted to be a leader in biopharma, I knew I needed to become more of a generalist in my knowledge base and experience.”
After holding senior level positions in various areas such as preclinical development, operations, and manufacturing, something interesting happened in 2011. “I had built a group in Pleasanton, CA and had begun filing patents to fill the R&D pipeline of Montigen Pharmaceuticals, a company we had acquired within SuperGen.” His group also had a lab in Utah, and the two began collaborating on small molecule discovery. But then SuperGen merged with Astex.
Pharmaceuticals leaving the company with four R&D operations. The decision was made to consolidate those four down to two, which meant closing the 20-person lab Redkar had built. “At that point I thought, maybe I should try my stint as an entrepreneur,” he states. His idea was to find a compound that would fit into that lab, thereby keeping most of the team intact, while building a company around it.
Working his network, Redkar came across a cytidine deaminase inhibitor (E-7727) owned by Eisai that made it possible to deliver cytosine-based nucleoside drugs in an oral pill. Eisai had decided to cut the program and were not going to make the payment to keep patent protection in place. Redkar saw potential. “We had worked on an oral cytidine hypomethylating agent for a long time, and we could combine it with E-7727 into one pill and form a small company around it.” He negotiated the terms with Eisai, and with the Astex CEO’s blessing, began creating a pitch deck. There was an understanding that he would found the new company outside of Astex, and Astex could choose whether or not to invest.
Redkar began forming a team, building out a board, keeping his CEO in the loop while also continuing to do his day job and pitching investors. “I thought I could put together a development program for about $500,000.” Considering Eisai had done a lot of work already on the asset, Redkar felt he could convince the FDA to utilize that information, along with the data from his company’s drug, to prove the drug’s safety in a combined form. That way, the company could work toward gaining an approval using a small Phase 3 trial of maybe 100 patients.
About a month into the process, Redkar received a call from Astex’ CEO asking, “What if Astex pays the half a million? If the program is as good as you say it is, convince some folks internally, convince the FDA, and then we can help you form the company.” His first entrepreneurial journey suddenly shifted back to that of the intrapreneur, having to convince colleagues that this two-drug oral combination was something of value. “People were not easily convinced, because we were working on a lot of new drugs and new pathways.” Fast-forward to the summer of 2020 and the drug, INQOVI, finally gained FDA approval for myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Although Redkar had left the company in 2016 to start his entrepreneurial journey in earnest, he takes delight in seeing his former colleagues succeed at bringing a new oral treatment to patients using only a 133-patient registration study.
Guo-Liang Yu – The Making Of An Entrepreneur
Guo-Liang Yu, Ph.D., cofounder, Chairman and CEO of Apollomics, came to the U.S. in 1984 to complete a Ph.D. “I joined Dr. Elizabeth Blackburn’s lab, and contributed quite a bit to her and Carol Greider winning the Nobel Prize in physiology or medicine in 2009.” Following a post-doc at Harvard, Yu was poised to become an academician, but got recruited to become a gene hunter at Human Genome Sciences (HGS) in 1993.
At HGS, Yu and colleagues sought to find genes with interesting biological function. Those newly identified molecules would then serve as drug targets to treat various diseases. He also continued his education, as HGS, being in Rockville, MD, was not far from Johns Hopkins University. “I took night classes for business law and marketing for a year to gain a better understanding for how businesses work.” He became very interested in patents, inventors, and inventions, and his “education” in that respect would continue as he worked at HGS. “When we were sequencing genes at HGS, we were taught to file patents on any molecule that looked interesting, along with how to do additional experiments to have strong claims protection.” As a result, today Yu is associated with more than 500 patents and has become an expert at strategizing IP protection. “When younger companies come to me for help, I always encourage them to build a strong patent portfolio.”
One of the molecules was Benlysta, which eventually was approved by the FDA. “Today, it remains the only drug discovered through the human genome project and is the only treatment for systemic lupus erythematosus (SLE),” he attests. Yu credits HGS as his first exposure to entrepreneurship. “I witnessed how HGS needed a multinational like GSK and support of the chemical market to bring a treatment to market.” And being that HGS was still very much a startup when he first joined, he also got to observe how management made decisions.
Preferring the Bay area, Yu moved back West and joined Mendel Biotechnology in 1998, before starting his first company, Epitomics, in 2001. “That was my first actual entrepreneurial experience that involved raising money, building a budget, delivering on what was promised operationally, and figuring out how to grow the company.” The company had two primary activities, building research tools and diagnostic reagents and developing therapeutic antibodies. The life science part was sold to Abcam in 2012 for about $170 million, while the therapeutic arm was spun out as Apexigen, an immuno-antibody company that is still in existence.
Having provided a fine return for investors and himself, Yu was recruited to join a CRO, Crown Biosciences in 2013. “At the time, many Chinese scientists who had trained in the U.S. were going back to China and building CROs to provide services to larger companies looking to enter the market,” he explains. But according to Yu, being good at science and being good at business are two different things, and as Crown wasn’t doing well financially, the board hired him in hopes he could turn it around. The process took about three years. Yu’s plan was to do what he had done with Epitomics – spin out a therapeutics company. But that new company would need a CEO.
Biopharma Startup Requires The Connecting Of “Preneurs”
Redkar and Yu met while each was serving on the advisory board of the University of Pacific (UOP) School of Pharmacy. Yu had told the dean of the college he was looking for a CEO for a startup, and asked if there was someone he could recommend. “He said, ‘Why don’t you see if Sanjeev is willing to jump out of a large pharma to become an entrepreneur,” Yu recalls.
At the time, Redkar was looking to pivot from being an intrapreneur to an entrepreneur, and Yu already was the cofounder on more than two dozen companies. The two began discussing entrepreneurship, and the topic of Crown Biosciences eventually came up. Crown had some oncology assets and was interested in seeing how these could be developed outside of China. Having spent his entire career focused on oncology, Redkar’s interest was piqued. “I spent the next three months reviewing information, got my China visa, and went over for a visit,” he elaborates. Seeing what he thought were gaps, Redkar spent the next four months creating a plan for how these compounds could be developed, along with how he’d pitch investors. He gave a convincing presentation to Crown’s board in 2015, and the decision was made to spin out the company. Redkar would be given some seed funding to lead the effort to build a team in the U.S.
But leaving an 18-year career as an intrapreneur was not an easy decision, because by now Astex had been acquired by Otsuka, and he had gained a fondness for how this company valued people. Plus, Otsuka was doing well financially. “I knew that becoming the CEO of a startup was going to involve a huge step down in salary and benefits,” he shares. He also understood that taking this position would place him in in a more generalist role, and if things didn’t work out, it may have been difficult to go back and apply for jobs as a domain expert. He deliberated for about a month, speaking to mentors, entrepreneurs, board members, and his family as he weighed the decision.
Resigning from Otsuka at the end of 2015, Redkar attended the annual J.P. Morgan healthcare conference (JPM) in January 2016. There, Yu introduced him to some people from OrbiMed, a life science venture capital group. Subsequently, Redkar conducted a formal presentation of the startup to OrbiMed. “I had begun putting together a development plan, but at that point, I was a single-person company.” He remembers the presentation involving about 15 to 20 people from OribMeds’ India, Asia, and New York offices, and how they deliberated about investing in a one-person company, something they, “normally never do.” But given Yu’s consistent success, they decided to make an exception, and agreed to provide the company $10 million to fund its series A. At the time, the company was registered in the Cayman Islands as CB Therapeutics (the CB coming from Crown Biosciences), and one of Redkar’s first tasks was to register the company in the U.S. Unfortunately, that name was taken. “I quickly had to decide upon a new name, which is how we ended up with CBT Pharmaceuticals.”
From One-Person Company To $125 Million Series C
Working as CEO, Redkar grew the company to seven employees and several pipeline assets by the end of 2017. At the same time, Yu was running Crown Biosciences, but near the end of 2017 the company was acquired. Redkar seized on this opportunity to get Yu more actively involved in CBT. “He was chairing our board, but I asked if he’d come on as CEO,” Redkar says. In turn, Redkar would take the position of president, and the two would apply a co-leadership approach. “I wasn’t really sure how this would work, but we determined that I would focus on all development and operational activities, while Yu would spearhead the funding along with building out an office in Hangzhou China. We’d collaborate on building the company’s strategic path.”
That plan worked out well, as early 2109 brought an announced $100 million series B – and a new name. “We were trying to come up with a better name for the company, and we recalled that our first combination trial was called APOLLO, derived from the Greek God of healing,” explains Redkar. That was written on the whiteboard. “Apollymi means to destroy,” he adds. That, along with others, also were added to the whiteboard. “Omics is a term used for large amounts of biological data, a coming together, if you will.” The three words were combined to come up with Apollomics, signify a group of people coming together to destroy cancer.
Now, with a new name and $100 million in the bank, the next steps were to hire a CFO and chief medical officer. These positions were filled in 2019, and by Q3 of 2020, the company had grown to approximately 50 employees, with about 30 in the U.S. and 20 in China. It even completed a $125 million series C financing in Nov. 2020, and has plans for building out R&D and manufacturing operations in China.
“Our dream is to build Apollomics into a cross-border innovation engine between China and the U.S., by conducting small clinical trials with equal representation between the two countries so a package can be registerable anywhere in the world,” Redkar says. For example, in January 2020, Apollomics announced an exclusive collaboration and license agreement with GlycoMimetics to develop and commercialize Uproleselan and GMI-1687 in greater China. GlycoMimetics already had received an FDA breakthrough therapy designation for uproleselan for relapsed/refractory acute myeloid leukemia (AML) in 2017 and has started a Phase 3 global clinical trial for uproleselan for that breakthrough indication. “We’ve negotiated with China’s National Medical Products Administration [NMPA] to do a Phase 3 bridging study for the same compound [APL-106 in the Apollomics portfolio] in combination with chemotherapy in r/r AML, with plans to borrow data readouts from the GlycoMimetics global trial to bridge our Phase 3, significantly speeding China development.”
Sounds like the entrepreneur is borrowing from his intrapreneurial toolbox. One compound at a time, Redkar and Yu move ever closer to achieving what every scientist dreams of – making a positive difference for humankind. And if you think about it, doesn’t that seem well aligned with what many Americans dream of?
“So even though we face the difficulties of today and tomorrow, I still have a dream. It is a dream deeply rooted in the American dream.” — Martin Luther King, Jr.
Sidebar 1: Leveraging The Best Of The U.S. And China
“We wanted to create a biopharmaceutical company with a slightly different business model,” says Guo-Liang Yu, Ph.D., cofounder and CEO of Apollomics. The company wanted to be in the U.S., as that is where the best scientific expertise and thinking still resides. But with China having more than 500 million people residing below poverty, that is where the most significant impact on global health can be had. However, Yu realized that, given the current state of geopolitical affairs, it would be difficult to run a business in China. Besides, Yu hoped that by having operations in both countries, the Chinese team could learn the best practices of their U.S. counterparts, and then apply those in developing products best suited for the Chinese market.
Given the current market, raising money does not seem to be a challenge for Yu. All of the funds Apollomics has raised thus far (i.e., $235 million) is of Chinese origin, although in U.S. dollars. “Sanjeev [Redkar] is handling the clinical operations and U.S. buildout, while I’ve been taking care of most of the finances and the China buildout,” Yu says.
One challenge they are experiencing is the big difference in market perceptions of value between the two countries. In the U.S., very few biotechs are willing or able to move into clinical development with multiple assets. “Most senior leaders and board members will typically agree that we should focus all our resources on the most promising asset.” But Yu says that’s not the culture of a Chinese biotech. “If you look at all the public Chinese biotechs, they have at least a dozen assets/molecules moving toward clinical development.” From his U.S.-trained perspective, having too many assets moving toward the clinic sends the signal that you really don’t have a strong lead candidate to begin with. “It is just a show, and something I still struggle with, as I have to think about how I’m being perceived as an entrepreneur to Chinese investors who might not yet see things the same as their U.S. counterparts.” So, one of the challenges is that by having operations in both countries, the company will be compared to other Chinese biotechs with lengthy pipelines, many of which Yu says don’t even make sense scientifically. “In China, some companies will count their assets as a means of deriving valuation to investors,” he explains. Regardless, he says the Apollomics approach is to put most of the company’s resources into its lead product, as that is the product that will either make or break the company.
Sidebar 2: Entrepreneurs Need To Be Good Storytellers
Guo-Ling Yu, Ph.D., is a highly successful entrepreneur who has served as co-founder of more than two dozen companies and made successful exits from at least two that provided handsome returns for investors and himself. But a venture never gets off the ground without money. And getting investors to want to give money requires an entrepreneur to be a good storyteller. With complicated science, sometimes this means having to “dumb things down.” Yu says when preparing to pitch his approach is to think from a layperson’s point of view and use a variety of metaphors. He then tests them to see which resonate best. This requires practice. “Try thinking about how you can ask a question so the other side can answer using the metaphor. That way you are facilitating communication and understanding instead of just forcing people to listen to what you have to say.”
Yu adds that leading in an entrepreneurial setting requires a whole different set of skills – and a willingness to change old habits. “You need to find a way to treat employees so that, if there are business challenges, they don’t immediately want to jump ship. And you need to make sure they are having fun while still putting in the long hours and workweeks that a startup requires.”
One more trait of a good entrepreneur is the ability to teach everyone in the company the importance of being frugal. Yu’s approach was to be overly transparent. For example, he remembers raising $1 million dollars for his very first startup, Epitomics. “I called a staff meeting and said, “I have good news and bad news. The good news is we now have $3 million. The bad news is that we as a company now have to generate a certain level of revenue and results if we hope to stay alive.” According to Yu, most scientists don’t often worry about the revenue component, because that’s not their responsibility. But in a startup, you need to train your scientists why they need to care about it, because biotech is a game of survival, and money needs to be stretched as far as possible to get to the next raise.
Finally, Yu says that being a good entrepreneur requires a change in mindset, from inductive thinking to deductive thinking. “Inductive thinking is: We have this technology, now what can we develop to sell to the market,” Yu explains. “Deductive thinking is: Here’s a market with an unmet need. Now, how can that need be satisfied?” In other words, inductive thinking is a solution in search of a problem, while deductive thinking begins with the end in mind.
BTPP 1: Have You Heard Of The Chinese Biopharmaceutical Association (CBA)?
The Chinese Biopharmaceutical Association (CBA) is one of the largest Chinese American professional associations in the U.S. It was founded in 1995 by Guo-Liang Yu, Ph.D., who today is the cofounder and CEO of Apollomics, an oncology therapeutic discovery and development company (to be featured in an upcoming issue of Life Science Leader). But back then, he was still at his first job, working as a “gene hunter” at Human Genome Sciences (HGS) in Rockville, MD. “At the time, HGS had a good group of Chinese scientists who had come from all over the country. Plus, with AstraZeneca, MedImmune, and the FDA and NIH nearby, it was a very nice biopharmaceutical community.” As such, Yu began discussing with his friends and colleagues the idea of forming some sort of association. “We could help one another as we became entrepreneurs, along with helping to bridge the gap between the U.S. and China, and academia and industry.” Twenty-five years later, CBA remains headquartered in Maryland, but now boasts more than 700 active members, over 8,000 registered individual members, and more than 100 institutional members. While most hail from the nearby geography, the association now has chapters in Canada and China. “When you set up such an organization, it is really important to put some thought around the bylaws.” For example, Yu only stayed one term as president, and insisted that each subsequent president do the same. “A CBA president needs to give to the community and grow themselves as leaders, but by limiting that responsibility to just a year, many more will gain the opportunity to learn, grow and lead,” he contends. “Every single CBA president has become successful, and many have gone on to found companies, with at least three now having gone public,” Yu contends.
BTPP 2: We Need To Expand How We Value Companies
During an interview for an upcoming feature in Life Science Leader, Sanjeev Redkar, Ph.D., cofounder and president of Apollomics (a biopharmaceutical company discovering and developing oncology treatments), discussed the topic of an exit strategy. “Are you looking to exit or leave a legacy?” I queried. “To build something,” he replied. But the question must have touched a nerve, as Redkar began to opine about how biopharmaceutical companies are valued. “We always evaluate companies based on their PE ratios, speed to market, return, stock price, and all that, but there is no value assigned to the social impact a company has,” he contends. Take J&J for example, which employs about 100,000 people globally. Depending on the size of the families associated with all those employees, that could equate to J&J helping to feed half a million people. “If J&J’s stock price goes up by 5%, and another public company employing 50 people goes up by 5%, the market treats them the same. But the social impact had by J&J is much more significant. As a society, this is something we need to figure out.” Redkar says that if you go to any financial or investment website, none will have anything recognizing the social impact those companies have on people. “Maybe we need a PE ratio to the number of employees employed,” he considers. “Sure, we’ve talked about being green, and there are metrics to measure a company’s sustainability, but that misses much of what I see as ‘social impact.'”