• Imprime PGG is a dectin receptor agonist that triggers anti-cancer immune responses
• IMPRIME 1 study enrolled 44 previously treated, metastatic triple negative breast cancer (TNBC) patients
• 15.9% Overall Response Rate (Three previous TNBC clinical studies with checkpoint inhibitor (CPI) monotherapies generated response rates of 5% to 6%)
• 25% Disease Control Rate >24 weeks
• 13.7 months median Overall Survival, with 64.2% patient survival at 12 months

EAGAN, Minn., June 01, 2019 (GLOBE NEWSWIRE) -- Biothera Pharmaceuticals, Inc. announced today primary data from IMPRIME 1, a Phase 2 clinical trial evaluating Imprime PGG, Biothera’s dectin receptor agonist, and KEYTRUDA^® (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc. (known as MSD outside the United States and Canada), in chemo-refractory metastatic triple negative breast cancer (mTNBC) patients.  The findings will be highlighted in a poster presentation at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Saturday, June 1 from 8:00 AM-11:00 AM Central Time.

“These early data suggest that Imprime PGG, which activates both the innate and adaptive immune response, in combination with anti-PD-1 immune checkpoint inhibitor therapy is a promising approach to cancer treatment, specifically triple negative breast cancer,” said Steven J. O’Day, M.D., the study’s principal investigator and Executive Director of the John Wayne Cancer Institute and Cancer Clinic at Providence Saint John's Health Center, Director of Providence Los Angeles Regional Research, and a Professor of Medical Oncology.  “These data clearly support additional research for this therapeutic combination.”

“These data represent compelling evidence that Imprime PGG, when added to immune checkpoint inhibitors, may provide substantial benefit for patients with triple negative breast cancer,” said Jeremy Graff, Ph.D., President and Chief Scientific Officer, Biothera Pharmaceuticals.  “Importantly, this study, which is heavy on translational research, shows not only clinical proof of concept but also mechanistic proof of concept for Imprime PGG. Accordingly, these data give us confidence in taking the next step to advance Imprime PGG further into clinical development.”

Key Findings from IMPRIME 1 in mTNBC
IMPRIME 1 data presented at ASCO (as of May 2, 2019) showed an ORR of 15.9% (n=7/44) among all mTNBC patients treated with the combination of Imprime PGG and KEYTRUDA, with one confirmed complete response (CR) (2.3%, n=1/44) and confirmed partial responses in six additional patients (13.6%, n=6/44).  An additional 38.6% (n=17/44) of patients had stable disease (SD) as best response.  The disease control rate (DCR) (CR + PR + SD > 24 weeks) was 25% (11/44 patients).  Median OS was 13.7 months by Kaplan-Meier analyses with a median time to follow-up of 12.7 months.  Projected OS rates are 79%, 72% and 64% at six, nine and 12 months, respectively.  Patients continue to be monitored for survival.

In addition, confirmed responses were evident in patient subpopulations with poor prognosis:  Patients with high lactate dehydrogenase (LDH) levels, visceral metastases and liver metastases.  The benefit for patients with liver metastases is unprecedented for KEYTRUDA alone.

IMPRIME 1 Response and Survival Data.  Previous checkpoint inhibitor monotherapy studies in mTNBC are shown for context.

	Bavencioc % (N=58)	Tencentriqb % (N=94)		KEYTRUDAa % (N=170)	Imprime PGG + KEYTRUDA % (N= 44)
Overall Response Rate	5.2	6.4		5.3	15.9 (7)
Stable Disease	26.0	13.0		18.0	38.6 (18)
Progressive Disease	65.0	64.0		60.6	40.9 (18)
Disease Control Rate
CR+PR+SD at any time	31.2	19.4		23.3	54.5
CR+PR+SD > 24wks	NR	10		7.6	25.0
Median OS in months	9.2	7.3		9.0	13.7*
Overall Survival Rate (%)
6 months	NR	60.0		69.7	79.0
9 months	~50.0**	44.0		50.0	71.5
12 months	37.1	37.0		39.8	64.2
CR = Confirmed Complete Responder PR = Confirmed Partial Responder NR = Not Reported # - ITT population, n = 44 patients, 2 not evaluable for response Latest IMPRIME 1 data from May 2, 2019.			* Median follow up time 12.7 months **Estimated from reported median OS a Keynote-086 Adams et al., 2018 - Merck b PCD4989g Emens et al., 2019 - Genentech cJavelin Dirix et al., 2018 - Pfizer

No concerning safety signals were observed in the study.  Overall, the treatment combination was well tolerated and the incidence of adverse events (AEs) was similar to safety observations in previous Imprime PGG studies involving more than 400 cancer patients and reflective of the disease and the known safety profile of KEYTRUDA.  Common AEs associated with the use of Imprime PGG include hypersensitivity/infusion-related reactions, generally of mild to moderate severity and frequently mitigated with administration of premedication. 

Study Design and Additional Data From IMPRIME 1
IMPRIME 1 is an open-label Phase 2 trial (clinicaltrials.gov, NCT02981303) evaluating whether Imprime PGG can enhance sensitivity to checkpoint inhibitors through activation of the innate and adaptive immune systems in metastatic TNBC patients who have failed one or more lines of therapy and were CPI-naïve.  A biomarker was used to select patients with ≥20ug/ml anti-beta glucan antibody who were most likely to respond to Imprime PGG.  Patients received Imprime PGG (4 mpk IV weekly) + KEYTRUDA (200 mg IV q3w) until disease progression or intolerable toxicity.

The primary endpoint was ORR by RECIST v1.1 and safety, and secondary endpoints included OS and DCR.  Pre- and on-therapy tumor biopsies were collected to assess immune activation at the tumor site.  The tissue samples showed that Imprime PGG induced heavy infiltration of activated immune cells (M1 state, PD-L1+) and activated CD8 and CD4 T cells.  On-treatment peripheral blood samples showed Imprime PGG-specific innate immune cell mobilization and activation, as well as enhanced T cell activation. 

“Immune activation was evident in both tumor biopsy tissues and in peripheral blood. These immuno-pharmacodynamic changes were evident as early as three weeks on treatment in peripheral blood and mark the patients who experienced the greatest clinical benefit,” said Dr. Graff. 

About Biothera Pharmaceuticals, Inc.
Biothera Pharmaceuticals is a privately held biotechnology company developing Imprime PGG, a novel dectin receptor agonist that reverses tumor-mediated immunosuppression while promoting antigen presentation to drive T cell activation and infiltration into tumors and to enhance clinical benefit from immune checkpoint inhibitors.  Biothera Pharmaceuticals is currently developing this platform drug through clinical research collaborations with Merck, Genentech, Dana Farber Cancer Institute and the Big Ten Cancer Research Consortium in cancers that include triple negative breast cancer, advanced melanoma, colorectal cancer and non-small lung cell cancer.

Contact:
Jeremy Graff, Ph.D.
President and Chief Scientific Officer
Biothera Pharmaceuticals, Inc.
651-675-0300
jgraff@biothera.com