Jeff Bockman: The State and Future of Immunotherapies

Jeff Bockman with Cello Health BioConsulting moderated the panel “Investing in Next Gen Immunotherapies” at the Biotech Showcase on January 7, 2019. Following the panel, the Investing News Network (INN) caught up with him to find out what his biggest takeaways were.

Bockman told INN he started the panel on a less than positive sentiment, from grasping the issues the immunotherapy industry has had, and where it was expected to be right now — “particularly combination” studies, he said. But, there has been “tremendous clinical success” from the checkpoint inhibitors with chemo, and “key combination approvals such as Anti-PD-1 agent with an Anti-CTLA-4.”

All of this circulates around a key theme: biotech and pharmaceutical companies have to learn lessons learned from developing immunotherapies, Bockman said. Because, as he said, the only thing that can fight back against tumors in real time is the immune system.

The immuno-oncology (I-O) combinations is where the trials have greatly fallen short. Bockman explains the rationale behind these trials is to increase patient responses to immunotherapies and with a longer and more durable remission. This brings combinations of other checkpoints with costimulatory agonists and with a variety of I-O types of modalities that are mostly antibody but also small molecules, he said. To date, these trials have “at best performed modestly, and in many cases have failed,” Bockman said.

On the small molecule side, IDO and many other co-stimulatory signals haven’t demonstrated the best value either, he said.

A key attribution towards the loss in robust clinical data for immunotherapies is that, business development has outpaced science. The appropriate steps weren’t taken Bockman said. “Everyone rushed into this, they didn’t do the necessary kind of scientific modelling.”

What could be done differently? Bockman said the biggest themes around developing immunotherapies better are: more and better types of animals studies, greater focus on the signals, more correlative translational work and gathering the necessary information, including if the drug failed. For the last point, Bockman explained, that the industry must “dive deeply into the reasons why something didn’t work.”

It’s easy to scrap a drug, but gaining perspective on why it didn’t work could be the answer the developing future drugs or improving the current drug — which brings back Bockman’s previous point of learning lessons from the development process.

On the business front, tensions exists between the business perception of immunotherapies and “the art of the science,” or clinical information, which backs up partnering and investing, he said. There has been so much enthusiasm for this field, but can be solved by a “maturing of understanding,” that the appropriate steps weren’t taken, he added.

This has left the industry with a pull back on an important benchmark of doing any type of licensing deal between pharma and biotech. These deals are “strong” or at least have “reasonable single-agent activity than a number of these modalities,” he said. The product of these deals was “de minimis” Bockman said.

The idea that adding something with activity to something with no activity, and expecting to see increased activity, hasn’t “panned out very well.” The result to this was “retrenching” to where oncology was before, which was seeing important single-agent activity in trials, he added.

The disappointing news from immunotherapy clinicals trials — especially this year — “underplays the great success that checkpoints have had,” Bockman said.

So, how can this sought after industry stay in investors’ limelight after a disappointing year? The maturing of understanding of I-O may temper the pace, or the size of deals for I-O, but it’s still clear how dramatic the effects can be, Bockman explained. “The immune system is a very significant player in all of these [deals],” and modulating it is important.

Bockman emphasized the diversity of targets and modalities and cell types investors can go after is “an embarrassment of riches,” even without mining all of these commodities appropriately.

As for the desirable industry, Bockman said some would say there may have been an “overemphasis on investing and deal-making around I-O.” He explained 90 percent of the top 10 upfront and total deals were in I-O over the last several years. Bockman calls this somewhat unfortunate, because those in the industry should recognize value to things aside from I-O.

Focusing on the greater immunotherapy market, non-I-O options are expansive. A kinase inhibitor to targeted mutations or somewhat standard antibodies are important too, he said.

Others include Agios’ (NASDAQ:AGIO) Tibsovo, which is a treatment for relapsed or refractory acute myeloid leukemia (R/R AML), targeting the IDH1 enzyme and was approved July 2018. FLT3 inhibitors, such as Astellas Pharma (TSE:4503) therapy XOSPATA wasapproved late-2018, which is also for R/R AML.

The US Food and Drug Administration also approved Abbvie (NYSE:ABBV) and Genentech’s Venclexta in June 2018 for chronic lymphocytic leukemia and small lymphocytic lymphoma with or without 17p deletion.

IDO is another immunotherapy that “shouldn’t be dead,” Bockman said. In April 2018, Incyte (NASDAQ:INCY) and Merck (NYSE:MRK) announced a failed Phase 3 clinical trial combination on the inhibitor. The trial was with Incyte’s epacadostat in combination with Merck’s KEYTRUDA.

Bockman believes IDO is a viable option, but it could be sequence dependent — meaning the order in which the drugs are dosed matters. Whether it’s a costim or something else, that does matter, he said. “There’s a lot of complexities,” he said, the panelists shared this sentiment but understand “you can only take it so far with the time and money.”

As for I-O, Bockman said there’s been a greater shift to “franchise expansion particularly with the big players from Merck with Keytruda and BMS (NYSE:BMY) with Opdivo.”

The overarching theme for immunotherapies is to, debulk and “get a handle of the tumor beyond what you might be able to do with surgery or radiation,” Bockman added. “We continue to need more tools and there have been a huge number of approvals that have not been I-O.”

In terms of I-O-I-O combinations, Bockman said there has been some favorable data, particularly from the European Society for Medical Oncology congress, in 2018. Dynavax (NASDAQ:DVAX), Checkmate and Idera (NASDAQ:IDRA) were a few companies to give credence to these combination studies, he said.

As for new data in 2019, Bockman said Nektar Therapeutics (NASDAQ:NKTR) and its partnership with BMS for NKTR-214 is one to keep an eye on. It’s first presentation had a lot of excitement at The Society for Immunotherapy of Cancer meeting in 2017, then “reduced in signal over time,” he said.

Howard W. Robin, CEO of Nektar, reported in the Q3 2018 financial results, the company is implementing the broad joint development plan across a range of tumor types, with the Phase 3 trial for melanoma in September and seven more to begin in the coming months.

Additional targets and readouts the industry is amping up for is oncolytic viruses and their combinations, vaccines, especially neoantigen vaccines — which should all have readouts in the next two years. Non-redirecting biospecifics may also have interesting data coming out.

Biotech startups are another key player in the immunotherapy market, such as Fate Therapeutics (NASDAQ:FATE) iPSC line. Novel immunotherapy twists such as Cellectis (NASDAQ:CLLS) and Allogene Therapeutics’ off-the-shelf CAR T immunotherapies are others to watch.

Adoptive cell therapies, neoantigens, novel modalities, checkpoints, tumor-specific antigens, CD-targets, NK cells, macrophages, fibroblasts and more will make an impact on the immunotherapy market. All of this is just touching the surface of the comprehensive ability of immunotherapies. Check out the video above for more information of the Bockman’s panel at the Biotech Showcase.

Don’t forget to follow@INN_LifeScience for real-time updates!

Securities Disclosure: I, Gabrielle Lakusta, hold no direct investment interest in any company mentioned in this article.

Editorial Disclosure: The Investing News Network does not guarantee the accuracy or thoroughness of the information reported in the interviews it conducts. The opinions expressed in these interviews do not reflect the opinions of the Investing News Network and do not constitute investment advice. All readers are encouraged to perform their own due diligence.