Immutep Quarterly Activities Report Q2 FY24

Media Release

• Excellent clinical data reported from TACTI-002 Phase II trial, including median Overall Survival of 35.5 months in first line non-small cell lung cancer (1L NSCLC) patients expressing PD-L1 (TPS ≥1%)
• Promising efficacy and tolerability data reported from INSIGHT-003 Phase I trial, including a strong Overall Response Rate of 71.4% in 1L NSCLC patients
• Late-stage & registrational trial progress:
  • 1L NSCLC: constructive regulatory feedback received for registrational TACTI-004 Phase III trial
  • First line head and neck squamous cell carcinoma: enrolment completed for TACTI-003 Phase IIb trial, and first data expected in H1 CY2024
  • Metastatic breast cancer: safety lead-in portion of AIPAC-003 Phase II/III trial completed early, with no safety or tolerability issues reported enabling the randomized portion of trial to commence
• Preclinical studies of IMP761, the world’s first LAG-3 agonist to treat the underlying cause of autoimmune diseases, continued. The Company is planning to begin first-in-human trials by mid-CY2024.
• Well financed with a cash balance of A$103.7 million, providing cash runway to early CY 2026

SYDNEY, AUSTRALIA, Jan. 30, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, provides an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 December 2023 (Q2 FY24).

EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in first line NSCLC
Immutep reported excellent new clinical data from the TACTI-002 trial evaluating efti in combination with KEYTRUDA® (pembrolizumab) at the ESMO Congress in October 2023. A median Overall Survival (OS) of 35.5 months was reported in first line NSCLC patients expressing PD-L1 (TPS ≥1%). Encouragingly, for patients with low PD-L1 expression (TPS 1-49%) median OS was 23.4 months, for patients with negative expression (TPS<1%) median OS was 15.5 months, and a median OS has not yet been reached in patients with high PD-L1 expression (TPS ≥50%).

New biomarker data from the trial was presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in November. The data demonstrated an early increase in immune cells (absolute lymphocyte count) was linked to improved clinical outcomes including OS. Significant increases of Th1 biomarkers (IFN-gamma, CXCL-10) and RNA levels of immune activating genes were observed in patients. Similar immune response biomarkers in the blood were reported previously from Immutep’s double-blind, randomised AIPAC Phase IIb trial, which combined efti with chemotherapy alone and did not include any anti-PD-1 therapy.

TACTI-003 (KEYNOTE-PNC34) – Phase IIb clinical trial in 1st line HNSCC
Enrolment was completed for the TACTI-003 trial in November 2023. A total of 171 first line head and neck squamous cell carcinoma (1L HNSCC) patients have been enrolled in this randomized, multicenter Phase IIb trial evaluating efti in combination with pembrolizumab in 138 patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumors (Cohort A) and in 33 patients with PD-L1 negative tumors (Cohort B).

The primary endpoint of the study is ORR of evaluable patients according to RECIST 1.1. Secondary endpoints include OS, ORR according to iRECIST, PFS, and DoR. Patients in Cohort A whose tumors express PD-L1 (CPS >1) are stratified by CPS 1-19 and CPS >20, and the clinical results for these CPS groups, as well as for patients in Cohort B with CPS <1, will be evaluated.

Immutep expects to report first data from TACTI-003 in H1 CY2024.

AIPAC-003 – Integrated Phase II/III trial in Metastatic Breast Cancer
The Company completed the safety lead-in portion of the AIPAC-003 trial evaluating for the first time 90mg of efti in combination with paclitaxel in 6 patients during the quarter. The treatment was well tolerated with no dose limiting toxicities. This good safety profile enabled the lead-in phase to be closed after the first 6 patients. Following the recommendation of the independent Data Monitoring Committee (IDMC), the Company proceeded into the randomized Phase II portion of study and is currently dosing patients. Currently 18 patients have been dosed in the randomized part.

TACTI-004 – Phase III registrational trial in 1L NSCLC
Immutep received constructive regulatory feedback from the Paul-Ehrlich-Institut (PEI), a German regulatory authority and part of the Committee for Medicinal Products for Human Use (CHMP), regarding the planned TACTI-004 trial of efti for 1L NSCLC in December. The PEI is supportive of Immutep moving ahead with the registrational trial evaluating efti in combination with an anti-PD-1 therapy in a chemotherapy-free regimen or as a triple combination approach that includes chemotherapy. Also, the PEI acknowledged the good safety profile of efti in combination with anti-PD-1 therapy.

Additional interactions with the FDA, other local European regulators, as well as with other stakeholders and potential partners are ongoing. Immutep plans to announce the final trial design for TACTI-004 in Q1 of CY2024.

INSIGHT-003 – Phase I in 1L NSCLC
Promising efficacy and tolerability data was presented from the INSIGHT-003 trial at the ESMO Congress 2023 in October. The trial evaluates efti plus anti-PD-1 therapy and doublet chemotherapy as first line therapy in non-squamous NSCLC patients. A strong ORR of 71.4% was reported, along with a Disease Control Rate of 90.5% and a 10.1-month median PFS. Median OS has not been reached, despite 81% of patients having low or negative PD-L1 expression.

In the difficult-to-treat PD-L1 TPS <50% patient population (i.e. those with cold or tepid tumors), the triple combination achieved a high 70.6% response rate and median PFS that exceeded 10 months in both low (TPS 1-49%) and negative (TPS<1%) PD-L1 patients, which collectively represent roughly 70% of the overall NSCLC patient population and remain an area of high unmet need.

In November, the INSIGHT-003 trial was expanded to four sites across Germany to support faster enrolment. Currently, 30 out of a total of 50 patients are enrolled. Recruitment is expected to be completed in 1H CY2024.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma
The first patient was enrolled and safely dosed in the investigator-initiated INSIGHT-005 trial, following the close of the quarter in January 2024. The study is evaluating efti and the anti-PD-L1 therapy BAVENCIO® (avelumab) in up to 30 patients with metastatic urothelial cancer and is jointly funded with Merck KGaA, Darmstadt, Germany.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma
The EFTISARC-NEO trial continued throughout the quarter, with 9 patients now enrolled and participating. The study will evaluate efti in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting. The trial is funded by a Polish grant program and is the first chemo-free triple combination therapy of efti as well as the first to evaluate the product candidate in a neoadjuvant setting. STS is an orphan disease with high unmet medical need and poor patient prognosis. Currently, Immutep expects first clinical data to be reported in H1 of CY2024.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE
IMP761 is the Company’s proprietary preclinical candidate and world’s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. Immutep is continuing its pre-clinical development and IND-enabling toxicology studies, which are necessary to evaluate the safety and toxicity of IMP761 before first-in-human trials can begin.

Immutep expects to begin the clinical development of IMP761 by mid-CY2024. Preparations for clinical development are ongoing.

PARTNER UPDATE: MONASH UNIVERSITY
Following the close of the quarter, Immutep entered into a research collaboration agreement with Monash University. The new agreement reflects an extension of the research collaboration agreements with Monash University signed in 2017 and 2020. Importantly, the new agreement will enable the parties to progress their investigations into the structure of LAG-3 and how LAG-3 interacts with its main ligand, MHC Class II. The research continues to be led by Professor Jamie Rossjohn at Monash University and Immutep’s CSO, Dr Frederic Triebel.

INTELLECTUAL PROPERTY
During the quarter, Immutep was granted a new patent for efti by the Korean Intellectual Property Office. The patent protects Immutep’s intellectual property for combination therapies comprised of efti and a chemotherapy agent which is oxaliplatin, carboplatin, or topotecan. The application was filed as a second divisional application and follows the grant of the first divisional patent, announced in 2022.

FINANCIAL SUMMARY
Immutep continued prudent cashflow management and strategic investment into its clinical trial programs for efti and preclinical program for IMP761 during the second quarter (Q2 FY24).

Immutep’s cash position remains very strong with a cash and cash equivalent balance as at 31 December 2023 of approximately $103.7 million. With an expected cash reach till early CY2026, the Company is well financed to reach key milestones that will potentially add value to efti and IMP761.

Cash receipts from customers in Q2 FY24 were $38k, compared to $132k in Q1 FY24. During the quarter, the Company received a $1.1 million cash rebate from the Australian Federal Government’s research and development (R&D) tax incentive program and a €1.6 million (~$2.6 million) R&D tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme (CIR).

The net cash used in G&A activities in the quarter was $0.8 million, compared to $1.6 million in Q1 FY24.

Payments of $427k to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration.

The net cash used in R&D activities in the quarter was $6.9 million, compared to $9.7 million in Q1 FY24. The decrease in cash used for the quarter was mainly due to the following:
1)   decreased clinical trial expenses since the TACTI-002 clinical trial is in close out phase;
2)   reduced contract laboratory services compared to last quarter; and
3)   decreased efti manufacturing activity.

Payment for staff costs was $2.2 million in the quarter compared to $2.3 million last quarter.

Total net cash outflows used in operating activities in the quarter were $5.5 million compared to $12.9 million in Q1 FY24.

About Immutep
Immutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com.

Australian Investors/Media:
Catherine Strong, Citadel-MAGNUS
+61 (0)406 759 268; cstrong@citadelmagnus.com

U.S. Investors/Media:
Chris Basta, VP, Investor Relations and Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com