Immunotherapy creates fresh challenges and tactical imperatives

Print 27 October 2015
Michael Fitzhugh / BioWorld

SAN FRANCISCO – With widespread excitement about immuno-oncology combinations driving deals, the pressure to find synergies has never been greater. The opportunities are creating new challenges for companies big and small, executives at the 2015 BIO Investor Forum said Tuesday.

"It's a very interesting time to be in the immunotherapy space," Heat Biologics Inc. CEO and founder Jeff Wolf told forum attendees. Combinations represent the future of the space, and the best hope right now for potential cures, he said.

Sitting beside him on the panel was Ben Thorner, vice president of business development and licensing for Merck & Co Inc. – a man more than a little familiar with the current excitement in the space, much of which has centered around exploring therapeutic combinations involving Merck's high-profile PD-1 inhibitor Keytruda (pembrolizumab), the first drug in its class to gain FDA approval, just over a year ago. (SeeBioWorld Today, Sept. 5, 2014.)

"For us, one of the challenges is thinking about the daunting number of cancer settings as well as combinations," said Thorner. "Probably at the top of our list as we put in place these clinical trial collaborations with partners is to try to come up with the best way to do studies to get a quick look at which are the combinations that are really going to have the most meaningful effect on patients."

Merck went from first-patient, first-visit in the first phase I study of Keytruda to approval of that therapy in about three and a half years, Thorner said. "We were able to do that by marshaling enormous resources to go really, really fast. We want to do that in the cases where there is the greatest degree of benefit for patients when it comes to combinations. The struggle right now is that we have more than 30 different combinations and clinical trials in different cancer settings," he said. Doing those studies in a way that leads to a quick reliable answer in any given target can be difficult.

At Heat Biologics – which has a market cap of $34.2 million vs. Merck's $144.78 billion market cap – the challenges are different. The speed with which the immunotherapy space is moving is, in and of itself, a force working against its efforts. "As you're going through clinical trials, new combinations are showing up and showing promise, which puts the smaller companies in a position of really having to sit back and strategically design their clinical trial to make sense in light of everything going on in the environment," said Wolf. "While companies like Merck and [Bristol-Myers Squibb Co.] have the resources to spend massive dollars on these huge all-comers trials, companies like ours need to be much more focused in how we direct our resources and how we combine with others," he said.

To that end, Heat recently embarked on a trial it's calling Durga, named for the Hindu war goddess with many arms. The multi-arm, open-label phase Ib trial is testing HS-110 (viagenpumatucel-L), the company's injectable adenocarcinoma cell vaccine, in combination with a PD-1 checkpoint inhibitor. In September, the first patient was enrolled in the trial to evaluate the safety, efficacy and tolerability of HS-110 in combination with Opdivo (nivolumab, Bristol-Myers Squibb Co.) with non-small-cell lung cancer who have failed at least one other therapy. A report of top-line objective response rates and six-month progression-free survival (PFS) data on the first 18 patients is expected to arrive by the end of 2016. Enrollment is ongoing. (See BioWorld Today, Sept. 2, 2015.)

There's still a lot of territory to cover, in terms of exploring possible combinations, but the panelists agreed companies are quickly moving up the learning curve. The way they approach the task – especially the approach of small companies looking to partner with larger ones – can make a tremendous difference in their eventual fortunes.

Olivier Lesueur, managing director of Bionest Partners, a life sciences strategy consulting firm, told forum attendees he advises his clients that the most important thing they can do is put together a compelling value proposition. "Invest in preclinical data," he said. "Show impact on tumor penetration. Show impact on the immunogenicity of the tumor. Show that you do not negatively impact immune functions."

While the models for measuring those things aren't great, Lesueur said, being able to show there's at least good reason to believe there will be synergy with an immunotherapy asset is key. And in that, Lesueur may have hit on the most important mission for any company meeting potential investors at this week's meeting, for what else are any of them looking for, essentially, other than a reason to believe?

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