By ADAM FEUERSTEIN @adamfeuerstein NOVEMBER 8, 2017Will tiny OncoSec break out with promising melanoma immunotherapy study results?
The addition of an experimental immunotherapy from OncoSec Medical (ONCS) to Merck’s (MRK) checkpoint inhibitor Keytruda is shrinking tumors in almost half of the skin cancer patients treated in a small clinical trial, according to updated results announced Wednesday.
That’s an encouraging tumor response rate, on par with what Incyte (INCY) has observed when its IDO inhibitor epacadostat is combined with Keytruda in skin cancer patients.
Similar results, so investors — besotted by all things cancer immunotherapy — must be equally enthusiastic about OncoSec and Incyte, right?
Nope, not even close. Incyte carries a $23 billion market value, with the still-unapproved epacadostat accounting for approximately half of that. OncoSec’s total market value: a microscopic $40 million. Shares of OncoSec closed Tuesday at $1.25.
Investors have largely ignored OncoSec’s approach to boosting patients’ response rates to cancer immunotherapy, but that might start to change with the updated data being presented Wednesday at the Society of Immunotherapy for Cancer (SITC) annual meeting.
Last month, Steve Cohen’s family office Point72 Asset Management disclosed a 5.7 percent stake in the tiny biotech company. An investment of that size is not even a rounding error for an $11 billion hedge fund, but it does show someone on Wall Street is taking notice.
OncoSec, just like Incyte and dozens of other competing drug companies, is trying to find a solution to a biologic roadblock that, to date, has limited the efficacy of checkpoint inhibitors like Keytruda or Bristol-Myers Squibb’s Opdivo to a minority of cancer patients. In melanoma, these drugs are generally effective in about one-third of patients.
Checkpoint inhibitors work by releasing the brake on the immune system, so these drugs are most effective against “hot” tumors already studded with T cells and other immune cells.
“Cold” tumors are largely resistant to checkpoint inhibitors because they lack significant engagement by immune cells. To extend the analogy, releasing the brakes on a car that’s missing an engine still doesn’t travel very far.
How to turn “cold” tumors into “hot” tumors? OncoSec’s approach is to inject “cold” melanoma lesions with DNA-based interleukin-12 (IL-12), a protein that activates components of the immune system. OncoSec then uses a short series of electric shocks (delivered with needles) to open the membrane of the tumor cells and help the IL-12 to enter.
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The company’s phase 2 study enrolled 22 patients with melanoma predicted to be unresponsive to checkpoint inhibitors based on findings from two biomarker assays. All the patients were treated with a series of electrically pulsed injections of OncoSec’s ImmunoPulse IL-12 directly into their melanoma lesions followed by standard intravenous delivery of Keytruda.
The results: Nine of the 21 evaluable patients, or 43 percent, responded to the IL-12/Keytruda combination treatment. Eight patients, or 38 percent, had a complete response.
After 15 months of follow-up, 57 percent of the patients have not experienced regrowth of their tumors, with a handful of patients followed for 18-24 months without progression.
OncoSec also analyzed samples of tumor taken from patients before and after treatment with the IL-12/Keytruda treatment, which showed increases in types of immune cells suggesting the tumors were being turned “hot.”
With the important caveat that cross-trial comparisons are challenging, the OncoSec IL-12 results presented Wednesday are not all that different from previously released results from Incyte’s phase 2 clinical trial of melanoma patients treated with epacadostat and Keytruda: an overall response rate of 56 percent, including complete response in 14 percent of patients. The median progression-free survival for the Incyte study was 12 months, with 49 percent of patients progression free at 18 months.
“From a clinical perspective, both drugs look very promising,” said Dr. Howard Kaufman, an oncologist at Massachusetts General Hospital and immediate past president of the SITC, when asked to make comparisons between OncoSec’s IL-12 therapy and Incyte’s epacadostat.
“What’s missing with both of these drugs, of course, are data from randomized controlled trials using a survival endpoint. We need to see those data first before drawing any conclusions, but there is potentially a role for both of these drugs in different patients,” he added. [Kaufman did not participate in OncoSec’s clinical trial but he was recently hired as the chief medical officer at a private biotech company developing engineered viruses to activate the immune system to fight cancer.]
Without a control arm, it’s impossible to determine precisely if OncoSec’s IL-12 therapy was responsible to the tumor shrinkage reported, or if the patients were simply responding to Keytruda alone. That is a fundamental weakness in the study results presented at the SITC meeting, although in fairness, the same criticism can be leveled against Incyte and its clinical trial.
However, OncoSec did enroll a handful of melanoma patients with tumors that continued to grow after prior treatment with a checkpoint inhibitor. The tumors in some of these patients later shrank when IL-12 was administered in combination with Keytruda, including a single patient with a complete response — a hint that OncoSec’s therapy was working as designed.
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OncoSec CEO Punit Dhillon described another important patient in the study: A pig farmer who was treated with IL-12/Keytruda after his melanoma lesions had already failed to respond to Keytruda, Opdivo, and Yervoy. Three months after the combination treatment began, the patient’s tumors stabilized, then started to shrink. He’s been followed for two years, still in partial response, said Dhillon.
The only way to know for sure if OncoSec’s therapy is working as designed is to test the combination of IL-12 and Keytruda in patients with melanoma confirmed to be unresponsive to Keytruda (or any checkpoint inhibitor) on its own.
OncoSec is enrolling just such a clinical trial, in collaboration with Merck. Study results are expected to read out in the middle of next year.
On Tuesday, Dhillon ceded the CEO role at OncoSec to Daniel O’Connor, the former CEO of Advaxis. Dhillon remains with OncoSec as president and retain his board seat.
Adam Feuerstein
Senior Writer, Biotech
Adam Feuerstein is STAT’s national biotech columnist, reporting on the intersection of biotech and Wall Street.
