Inhibrx CEO Mark Lappe was particularly keen on INBRX-106’s performance in patients with HPV-positive disease and sees a nearly $4 billion near-term opportunity thanks to the Phase 2 results.
Patients with head and neck cancer who took Inhibrx Biosciences’ OX40 receptor agonist in combination with Merck’s Keytruda responded at a higher rate than those who took Keytruda alone in a Phase 2 trial, clearing the way for the biotech to access what executives estimate is a $50 billion-plus market.
INBRX-106 was tested in the Phase 2 HexAgon study in patients with treatment-naive, PD-L1 positive metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC). The interim analysis comes from 68 total patients across the treatment and comparator arms.
As of August 19, patients taking INBRX-106 plus Keytruda (also known as pembrolizumab, or pembro for short) had a confirmed objective response rate (ORR) of 48.3%, as compared to 26.5% for the Keytruda-only arm, according to a Tuesday release. Four patients in the combo arm, which included 29 total patients, had a complete response, whereas none achieved that in the Keytruda-alone bracket. Confirmed ORR was the main goal of the trial.
“Pembro releases the brake on the immune response. 106 is designed to step on the accelerator. This is the clinical evidence that the accelerator is working,” CEO Mark Lappe said on a Tuesday morning call with investors.
Despite Lappe’s positive tone, shares of Inhibrx fell more than 18% to $98.56 as the markets opened on Tuesday.
Lappe heralded the readout as the clinical validation of the OX40 target, which others have tried to take on but failed. Previous attempts have used bivalent antibodies, which Lappe said do not bring together enough OX40 receptors to effectively activate the T cells to fight the cancer.
“The field may have had the right target but the wrong molecular architecture,” Lappe explained. INBRX-106, meanwhile, is a hexavalent OX40 agonist, engaging six receptors at once.
On safety, there were a higher number of treatment-emergent adverse events in the combo treatment group, however they were mostly low-grade. There was a higher rate of discontinuation in this group as well, but Lappe said there wasn’t a clear pattern to the events. The most common events were rash, fatigue and diarrhea.
Lappe was particularly keen on INBRX-106’s performance in patients with HPV positive disease. In this group, there was an 80% confirmed overall response rate, compared with 33.3% for Keytruda alone. Moreover, 30% of patients with HPV+ disease responded completely.
“We believe the HPV positive data are the first clinical expression of a much broader biological opportunity for 106,” Lappe said.
This group also saw 90% progression-free survival (PFS) at six months as compared to 33% in the comparator arm. Median PFS for the combo treatment group had not been reached as of the six-month cut off in August, whereas the Keytruda-only group had a median PFS of 4.6 months.
The CEO believes that the HPV+ results stem from greater antigen recognition in these patients. Inhibrx will now amend the Phase 2 study to add 50 more HPV+ patients to further explore this population.
The ORR results for the HPV+ group could open the door for an accelerated approval in HNSCC for patients with HPV+ disease, Lappe said.
Lappe predicts that the first market opportunity for INBRX-106, if approved, will be recurrent and metastatic HNSCC. The U.S. market in this indication alone could be worth about $1 billion in 2029, he said. Inhibrx is eyeing a launch in 2028, based on an accelerated approval timeline.
“But recurrent and metastatic disease is only the starting point. If we move into earlier stage HPV-positive disease, the opportunity becomes substantially larger,” Lappe said.
If INBRX-106 moves into first-line and pre-surgical patients, the U.S. market could expand to more than $4 billion. Lappe said physicians are actively seeking better options for these patients, as the current treatment paradigm includes debilitating radiation and surgery.
“We believe the magnitude of the clinical benefit we are seeing, combined with a relatively concentrated patient population, also creates an opportunity for premium pricing,” the CEO added. He did not name Inhibrx’s intended price but pointed to the “depth and durability of responses” to back up a “meaningful duration of therapy.”
A broader market opportunity
Inhibrx has even greater aspirations for INBRX-106—and the OX40 class in general.
“We believe HPV-positive head and neck cancer is the beginning of the opportunity, not the boundary of it,” Lappe said.
He said the mechanism could be used in immunogenic tumors, which include massive indications like non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, triple-negative breast cancer and bladder cancer.
“These are tumors with substantial pre-existing immune engagement, making them very logical settings in which to test whether 106 can amplify an existing anti-tumor immune response,” Lappe said.
INBRX-106 is already being tested in combination with Keytruda in a Phase 1/2 trial for solid tumors, including NSCLC. Lappe said Inhibrx has already noted some “nice activity” in later-line NSCLC. A separate investigator-instigated study is looking at the therapy in breast cancer, where immunotherapy has not shown a complete response in the pre-surgery population, Lappe noted.
Another area for expansion is in combination with the emerging class of neoantigen cancer vaccines, such as Merck and Moderna’s intismeran autogene. The personalized mRNA vaccine improved outcomes in patients with melanoma in a Phase 3 trial that read out last month, surprising analysts and investors alike.
“The vaccine primes a tumor-specific T cell response, and 106 is designed to expand and sustain it,” Lappe explained. “We believe bringing these two powerful complementary mechanisms together could be transformative and create a new paradigm in cancer immunotherapy.”
Analysts wondered if this was a new idea seeking to capitalize on Moderna and Merck’s groundbreaking data. Lappe insisted that Inhibrx had been looking into the idea prior to the companies’ recent results. He said Inhibrx plans to get clinical work underway next year to explore the combination of an OX40 agonist and neoantigen cancer vaccines.
“We really felt this is very compelling. We felt that before the Merck-Moderna results came out,” Lappe said. “I think this is going to be an area where you’re going to see really exceptional synergy.”
In April, Inhibrx emerged as a potential M&A target, with Merck in particular being an interested party, according to a BMO Capital Markets note. The biotech could be valued at about $9 billion and spark a bidding war, with Japan’s Ono Pharma also potentially interested, according to a Reuters report.
