BOSTON – For investors, immuno-oncology (I-O) is still proving "very hard" to buy into, said Christiana Bardon, portfolio manager at Burrage Capital, during a panel session at Biopharm America. "Honestly it was hard from the get-go. If you think about the original ipilimumab data that came from [Medarex Inc.], it was not obvious that [the drug] worked, right? It was like a head fake, actually. Now we're anxiously looking for the next-gen, but the truth is we've been utterly unsuccessful."

New York-based Bristol-Myers Squibb Co. first won FDA clearance for ipilimumab, branded Yervoy, for late-stage melanoma in the spring of 2011. (See BioWorld, March 28, 2011.)

Part of what's difficult with I-O therapies is that preclinical data have no predictive value, Bardon said. "There's no monotherapy efficacy in a lot of these situations by virtue of the nature of the mechanism, and then we have to go to combos," which makes evaluating the action of the drug more complicated. She pointed to "a number of dead bodies along the way," citing indoleamine 2,3-dioxygenase (IDO) inhibitors. (See BioWorld, Jan. 5, 2018.)

"I think what we need is better biomarkers," Bardon said. "Right now, responses in early clinical trials are not enough for us, because they don't happen. What we need to do is take a lot of tissue [and] do a lot of pathology. We need to really understand what histological correlates actually generate immune responses that contribute to clinical outcomes. That's been very complex. Honestly, we haven't been doing the work. The early IDO studies did not do any histological biomarker work at all. They just ran to it because the early data looked so good."

The session, called "What's Next: 2020 and Beyond," was moderated by Roger Kitterman, vice president at Partners Healthcare. The topic is "always dangerous, because we're going to be wrong, but we have some ideas. If you were to have this panel 10 years ago, we probably would be talking about how aptamers might be taking on antibodies, because that could be the new modality moving forward. On the digital side, doesn't everybody have to have a Second Life presence? Because you have to have your avatar there."

Bardon singled out cell therapy, saying researchers have "just opened the door to that new room" with the first few approvals. "It's been a little slow to launch because there's obviously a lot of executional issues with regard to administering autologous cell therapy," though efficacy has proved unparalleled, with 60% to 80% complete response rates in indications such as pediatric acute lymphocytic leukemia. Such an approach may eventually tackle solid tumors as well, she predicted. "The other turn that cell therapy may take over time is to be allogeneic instead of autologous. There you [would] have an off-the-shelf therapy with incredible efficacy which can be administered just as a pill or protein therapeutic." The strategy is being tried outside of oncology as well, she noted, calling out Boston-based Vertex Pharmaceuticals Inc.'s recent deal to take over Semma Therapeutics Inc., of Cambridge, Mass., for $950 million in cash to bring aboard a potential cure for type 1 diabetes. Privately held Semma deploys stem cell-derived human islets and has proved able to make large quantities of functional human pancreatic beta cells that restore insulin secretion and ameliorate hypoglycemia in animal models. The company has invented a device that encapsulates and protects those cells from the immune system, which means durable transplants and no immunosuppressive therapy. (See BioWorld, Sept. 6, 2019.)

Partnering, investor attendance up

Christiana Iyasere, director of the department of medicine innovation at Massachusetts General Hospital and co-founder of Dyrnamix Inc., likes the prospects for informatics and machine learning as well as digital health. "Over the past 10 years, we've had this wealth of data but very little information," she said, and "it's really just been over the past two to three years that we've seen this transition" from focus on isolated findings to what might be clinically actionable. There also has arisen the ability to "de-convolute" biological systems previously tough to puzzle out, such as the relationship of RNA to disease. Lexington, Mass.-based Dyrnamix focuses on extracellular RNA (exRNA) in the bloodstream of patients, which reflects the dynamic state of cardiovascular disease pathology and can be used to understand individual patient risk of cardiac events. Unlike many established biomarkers, exRNAs are implicated in disease pathogenesis and, the company said, may serve as functional biomarkers to risk-stratify patients as well as diagnostics to guide therapy or target selection.

Chandra Ramanathan, head of Leverkusen, Germany-based Bayer AG's East Coast Innovation Center, said he wants the field in times ahead to muster the "courage to challenge some of the thinking" about the size of experiments. Panelists discussed how studies in certain daunting oncology indications such as pancreatic cancer may pass regulatory muster with smaller, shorter trials, while others with similar mortality rates may be huge and last for years.

Asked what might be hot next, Bardon suggested that "DNA repair and the poly ADP ribose polymerase [PARP] mechanisms related" to it are going to be "very important over time," outside of BRCA applications. She recalled that in December, with oral PARP inhibitor Zejula (niraparib) well on its way to blockbuster status, London-based Glaxosmithkline plc paid a premium to pick up developer Tesaro Inc., of Waltham, Mass., in a deal valued at about $5.1 billion. The drug was approved in March 2017 for recurrent ovarian cancer. (See BioWorld, March 28, 2017, and Dec. 4. 2018.)

With about 600 attendees, Biopharm America once again is held in conjunction with Biotech Week in Boston. The number is about the same as last year, said Kari Bennett, vice president of marketing for EBD Group, but one-on-one partnership get-togethers (which Biopharm is uniquely structured to set up) have increased 20%. Also, the involvement of reps from the investment community, such as venture capitalists, has increased by 100%, from about 50 to 100. Biopharm America continues through today.

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