On December 10, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune disease, reported encouraging first Overall Survival (OS) follow up data from its ongoing Phase IIb AIPAC study evaluating Immutep’s lead product candidate eftilagimod alpha in combination with paclitaxel chemotherapy ("efti group") in comparison to a combination of placebo and paclitaxel chemotherapy ("comparator group") in patients with HER2-negative/HR positive metastatic breast cancer (HR+ MBC) (Press release, Immutep, DEC 10, 2020, View Source [SID1234572650]). These data were selected to be presented in a spotlight presentation at the San Antonio Breast Cancer Symposium 2020, which is being held virtually this week from Texas, USA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AIPAC Principal Investigator, Hans Wildiers of University Hospital Leuven, Leuven, Belgium, said:

"Improving Overall Survival is a key endpoint when evaluating the benefit of new anticancer drugs. Efti is a new drug targeting the immune system in an innovative way and has the potential to improve outcomes in HER2-negative/hormone receptor positive metastatic breast cancer patients. The AIPAC study investigated efti in combination with first line chemotherapy in this population, a group of about 250,000 patients diagnosed worldwide each year. Although the progression free survival data in the efti group did not show a significant improvement versus the comparator arm in AIPAC earlier this year, the OS data in general looks already very interesting and will mature further. The OS data in subgroups such as those below age 65 years are highly encouraging and may lead to more effective treatment options for metastatic breast cancer patients."

Immutep CSO and CMO, Dr Frederic Triebel said: "We are very excited to see that efti is boosting the immune system by providing a statistically significant increase in CD8 T cell numbers, which is correlated with prolonged survival for patients. These data provide proof-of-concept and support our long-held belief that efti can provide a meaningful benefit to patients in a range of cancer settings by "pushing the

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

LOGO

gas" on the body’s immune system, representing an important landmark. Through this mechanism, efti is helping a large proportion of patients in the AIPAC study with Her2-HR+ metastatic breast cancer which is typically a non-immunogenic cancer and is therefore significantly less responsive to modern immune checkpoint inhibitor (ICI) therapies. As such, chemotherapy continues to be the standard of care in many instances and there continues to be a large unmet medical need. We look forward to reporting final survival data in 2021."

Immutep CEO, Marc Voigt said: "AIPAC marks an important milestone for Immutep and builds our confidence that efti is beneficial for many cancer patients, including those with metastatic breast cancer. Notably, we have seen a more material OS benefit than PFS benefit in this study; however, we note that this is not unusual for some immunotherapies where it can take time for the body’s immune system to be boosted and provide a therapeutic benefit. We are very encouraged by these first OS results which, subject to ongoing data collection, warrant a registrational perspective and regulatory interactions towards what we hope will be an important new class of medicines."

Key Efficacy Results: data cut-off 24 September 2020

In the total patient population, first OS data (based on approx. 60% of events) show that patients in the efti group had an improving OS trend with a median OS of 20.2 months compared to 17.5 months for patients in the comparator group, indicating a survival benefit of +2.7 months (HR = 0.83; p = 0.14). The OS analysis is based on a 2-sided false positive probability of 0.05. Furthermore, a significant deterioration in quality of life was observed for patients in the comparator group at week 25, which was not observed in the efti group. This is an encouraging observation as these types of benefits are supportive of efti being eligible for reimbursement upon marketing approval.

In key predefined patient groups, the study has already demonstrated a statistically significant and clinically relevant OS benefit from treatment with efti in combination with chemotherapy. Patients under the age of 65 years (representing 66.7% of patients in the efti group) reported a median OS of 21.9 months compared to 14.8 months in the comparator group, indicating a survival benefit of +7.1 months (HR = 0.62; p = 0.012) favoring the efti group.

Figure 1 – Kaplan Meyer curve OS for patients < 65 years

The current data suggest that for patients younger than 65 years old, the probability of being alive at three years with efti plus chemotherapy vs. chemotherapy alone is increased by 100%.

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Furthermore, patients with a low monocyte count at baseline (representing 21.9% of patients in the efti group) reported a median OS of 22.4 months compared to 12.9 months in the comparator group, indicating a survival benefit of +9.4 months (HR = 0.47; p = 0.02) favoring the efti group.

Trending towards statistical significance, patients with a more aggressive, more immunogenic luminal B type of breast cancer (representing 48.8% of patients in the efti group) reported a median OS of 16.3 months compared to 12.6 months in the comparator group, indicating a beneficial trend of +3.8 months (HR = 0.69; p = 0.077) favoring the efti group. (See Table 1)

Table 1 – Overall Survival in key patient groups

Note: A lower HR, means a reduced risk of death, e.g. by 53% in the low monocyte group.

Immuno Monitoring Results

Importantly, there was a statistically significant, sustained long-term increase in peripheral CD8 T cells in patients in the efti group. This is consistent with the mode of action of efti. There was also a statistically significant correlation between those patients having an increase in the number of CD8 T cells and those having a prolonged OS. This represents a strong proof-of-concept in a randomised, double blinded setting.

Safety

The combination of efti and paclitaxel chemotherapy was overall safe and well tolerated, further building upon efti’s strong safety profile to date.

The presentation poster is available at www.immutep.com/investors-media/presentations.html.

Next Steps

Multivariate analysis of the data is ongoing and final OS data is expected to be reported in mid 2021.

Webcast Details

Immutep will present this AIPAC data in a global webcast for investors, details are as follows:

•
Date & Time: Friday, 11 December 2020, at 8.30 am Australian Eastern Daylight Time (AEDT) (Thursday, December 10th, at 4:30 p.m. U.S. ET)

Register: View Source

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Questions: Investors are invited to submit questions in advance via [email protected].

A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the AIPAC trial

Active Immunotherapy Paclitaxel (AIPAC) is a multicentre, placebo-controlled, double-blind, 1:1 randomised Phase IIb clinical trial in HER2-negative/HR positive metastatic breast cancer.

The study is evaluating the combination of Immutep’s lead product candidate, eftilagimod alpha (efti, LAG-3Ig or IMP321), and paclitaxel chemotherapy. 227 HER2-negative/HR positive metastatic breast cancer patients are randomised 1:1 to a chemo-immunotherapy arm (efti plus paclitaxel) or to a comparator arm (placebo plus paclitaxel). Patients receive weekly paclitaxel at days 1, 8 and 15, with either efti or placebo injected subcutaneously on days 2 and 16 of each 4-week cycle, repeated for 6 cycles. Thereafter, patients pass over to the maintenance phase with efti alone.