Take Charge of Your Career but Leave Room for Serendipity

By Marie Daghlian

There’s no one way to rise to the top said the four women sitting on the stage at Women in Bio’s mid-March event held at JLABS in South San Francisco as part of Women’s History Month, which recognizes and celebrates women’s accomplishments. Under the auspices of the event’s working title, “Leveraging Partnerships in the Growing Immuno-Oncology Space,” the evening of networking and education drew an enthusiastic crowd of mostly women, but also a smattering of men, who were all there to take charge and further their careers.

This certainly seemed to be the case as attendees, who included academics, postdocs, small and big company researchers, and members of the legal, financial, and investor professions, freely introduced themselves to one another and chatted away while snacking on hors d’oeuvres. After a lively hour of networking ahead of the evening’s talk, moderator Stacy Feld, vice president of Consumer Venture Investments and External Innovation at Johnson & Johnson Innovation-JJDC, led a three-person panel in a wide-ranging discussion not only of trends and partnering in immuno-oncology, but also of how each of them got to where they are now. Through it all ran the theme of making room for serendipity—taking advantage of the chance opportunities that present themselves.

Panelists included Dr. Julie Hambleton, vice president and head of US Medical at Bristol-Myers Squibb; Jane Grogan, PhD, head of Adaptive Tumor Immunity and principal scientist at Genentech; and Sylvaine Cases, PhD, vice president of Oncology Scientific Innovation for Janssen Research and Development and the J&J California Innovation Center.

Stacy Feld, who started her career as a lawyer and worked in business development at Genentech and Third Wave Technologies before becoming a venture capitalist, set the stage by describing immuno-oncology, or I-O, as “the exploding supernova and the third paradigm in drug discovery after cytotoxic therapies and targeted molecular therapies.” Immunotherapy works by stimulating the patient’s immune system through a T-cell mediated response, to fight and eradicate cancer. She noted that there are more than 1,000 ongoing I-O clinical trials according to Clinicaltrials.gov, which makes for a robust partnering environment.

According to Feld, the space accounted for more than fifty percent of deals struck by private companies, and venture capital has poured more than $1 billion into I-O over the past couple of years. Biopharma company efforts in the space have resulted in twenty new drugs and diagnostics approvals and label extensions in the US and Europe that are expected to generate sales of more than $7 billion.

There’s still a long way to go, though, as exemplified by Juno Therapeutics’ halting of its CAR-T therapy study, and the fact that we are still a long way from curing cancer. But immunotherapies hold promise for improving the lives of many cancer patients.

“That’s what we’re excited about—helping patients in a new and novel way,” said Feld.

Before getting deeper into discussing partnering in I-O, the panelists briefly described how they got to where they are now. Julie Hambleton started her career as a nurse before getting a medical degree and spending 17 years at UCSF as a postdoc and faculty member. From there she worked at a couple of small biotechs before joining Genentech, and then moving to Big Pharma at Bristol-Myers Squibb.

Serendipity played a big part in her career, she said: “none of what you do is wasted.”

Jane Grogan, an Australian, has been at Genentech for twelve years where she works across early discovery research, clinical development, and business development. As an undergrad, she didn’t want to do science so she started a radio show called “Lost in Science.” Although NPR picked it up, she soon wanted to be on the expert side of the interview table. She went back to school and got her graduate degree in the Netherlands, and worked as a Howard Hughes Fellow at UCSF before going to Genentech. Ironically, she said, she’s now hosting a biweekly podcast called “Two Scientists Walk into a Bar.”

Sylvaine Cases always wanted to be a scientist. She was trained in France but has never worked there. She came to the US to work at the Gladstone Institutes where she learned all she could about cancer research. That knowledge and being French got her a job as senior director of business development at Sanofi based in California. “I have been driven by curiosity,” Cases said. “Sometimes an opportunity is not exactly what you had in mind,” she disclosed about why she ended up in business development instead of in a lab. She joined J&J only recently.

From there the discussion turned to immuno-oncology. Hambleton said Bristol-Myers Squibb has been in the forefront of “breaking the code of immuno-oncology.” The traditionally separate fields of oncology and immunology have similarities, she noted: “Whether you’re trying to activate the immune system for oncology or suppress it for autoimmune diseases, a lot of the pathways and science are the same.”

Although Janssen, J&J’s pharma division, doesn’t own a therapeutic agent targeting PDL1 or CTLA4, two common targets for immunotherapeutics, it is one of the most active areas for investment in R&D there. With fifteen molecules in the I-O pipeline, the company relies heavily on partnering, Cases said, which sometimes starts with the innovation at JLABS.

The panelists talked about the explosion of clinical trials in the space and the high level of competition. Many immunotherapies are being developed to work in combination with targeted therapies, and the accelerated approval pathway presents challenges because you have to have enough data to show the contribution of each single agent and then the contribution of the combination. It’s challenging to get patients enrolled, Hambleton said, because most of the large biopharmaceutical companies are targeting the same areas, and going after the same investigators. Many companies conduct clinical trials globally, and a lot of oversight is needed.

Grogan noted that it is harder to find treatment naïve patients for studies. There is also the fact that I-O therapies work in conjunction with checkpoint inhibitors. “At Genentech,” Grogan said, “we know the I-O biology makes sense always on top of checkpoint inhibitors. It doesn’t work on its own.”

Feld noted that clinical outcomes data and real world data is outpacing the knowledge of the biology of cancer. Can academics be leveraged to manage the data, she asked?

Grogan said that it’s a problem because we don’t understand the immune response to cancer. “Cancer has been treated by oncologists, not immunologists,” she said. “As we begin to understand the biology, our whole way of thinking about immunology is going to change. We’re learning how cells infiltrate tissue and how they maintain for a very long time. The more we learn about the pathogenesis, the pathophysiology of tumors, the more we are going to understand immunology to probe questions and come up with new drugs. I think this will take a long time.”

Everyone is collecting data and interrogating it in different ways. The field is struggling, Grogan said. She thinks it would be a good idea to pool some of the data and share it. “The data is only as good as the questions asked of it,” said Grogan.

Hambleton noted some initiatives that make use of shared data, for example, the Obama Administration’s Moonshot program to accelerate finding cures, and the goals of the Parker Foundation. She talked about the need for standardization as to what biomarker data is collected and how the tumor system is assessed. “Can we come up with some agreed upon rules to set standards so that when we interpret results, we can all be doing it the same way?” she asked.

The discussion moved on to partnering and what companies that want to partner with Big Pharma need to present as far as biomarker data and early stage study results.  Because it is such a hot space, companies think their molecules are worth a lot, but the reality is that you still need the science behind the molecule to convince anyone to put it into combination, noted Genentech’s Grogan.

Besides the science, you need to practice your pitch, and ask good questions, said Hambleton. “It puts you into the driver’s seat and a position of strength,” she said.

Grogan said you have to be honest. And Cases said you have to know how you can help the pharmaceutical partner fill a gap. Know what’s in it for yourself before you go into a partnering meeting, she said.

After a brief question and answer period, Feld closed the meeting by asking the panelists to relate a critical moment or event that helped them take charge of their careers. For Grogan, it was to stop having a postdoc mentality, waiting for the professor to pat you on the head for a job well done. For Cases, it has been being bold, and curious: “I started asking questions at conferences and people began remembering me in the lunch line.” For Hambleton, it was knowing herself and being honest—asking questions and as a doctor, providing patients with value.  She also allowed for serendipity. “I do the journey for its own sake,” she said. “I don’t have an end goal in mind.”

Charged up after the lively panel discussion, attendees networked with each other for another hour at the closing reception while they viewed the dimming light of sunset over the San Francisco Bay.