Immutep Quarterly Activities Report & Appendix 4C

Immutep Quarterly Activities Report & Appendix 4C 

• Immutep entered late-stage development in the newly validated LAG-3 space 
• Data from 1st line NSCLC and 2nd line HNSCC presented at ASCO 
• Efti to be evaluated in new triple combination therapy trial and entered into a new collaboration with Merck KGaA for efti and bintrafusp alpha 

Sydney, Australia, July 14 2021 – Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a biotechnology company developing novel LAG-3 related immunotherapy treatments 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 30 June 2021. 

“In the past quarter Immutep has entered a new phase as a biotech company at the forefront of the LAG-3 immunotherapeutic landscape. We are now advancing the development of efti in multiple different cancers and have the ongoing support of large pharma collaboration partners, including MSD and Merck Germany, for many of our trials. We have begun planning for our new Phase III study in metastatic breast cancer which, if positive, could provide us with registration data and have a number of new and ongoing other trials progressing at pace. Manufacturing scale up of efti to potential commercial quantities is progressing well,” said Marc Voigt, CEO of Immutep. 

“All of this company activity is taking place in an exciting LAG-3 landscape where the interaction between MHC class II and LAG-3 has just recently been validated as a therapeutic mechanism for regulating the body’s immune system to fight cancer. With more LAG-3 related programs under development than any other biotech or pharma in the space, we are very excited about the future,” he concluded. 

Efti Development Program 

AIPAC - Phase IIb clinical trial - ongoing 
The trial is on track to report final overall survival (OS) data in H2 of calendar year 2021. Immutep previously reported OS data from approximately 60% of events in Dec 2020. 

TACTI-003 - Phase IIb clinical trial - new 
Immutep received Fast Track designation in 1st line recurrent or metastatic head and neck squamous cell 
carcinoma (HNSCC) from the United States Food and Drug Administration (FDA) in April 2021. This opens the potential for expedited development and review of efti in 1st line HNSCC with the FDA. 

Following the close of the quarter, Immutep completed the necessary regulatory steps with the US FDA and obtained institutional review board approval in the US to commence the TACTI-003 trial. Patient recruitment is expected to begin in this quarter. 

TACTI-002 (also designated KEYNOTE-798) - Phase II clinical trial – ongoing 
At ASCO 2021, Immutep reported updated interim results from TACTI-002 showing the combination therapy of efti and pembrolizumab demonstrates a very favourable overall response rate (ORR) together with very encouraging duration and depth of response in 1st line non-small cell lung cancer (NSCLC) (Part A) and 2nd line HNSCC (Part C). Tumor responses were seen in all PD-L1 subgroups, including in low PD-L1 expressing patients which are typically less responsive to anti-PD-1 therapy. Importantly, the combination therapy continues to be safe and well tolerated. 

Recruitment continues for the additional 74 1st NSCLC patients for the expansion of Part A, with 33 patients already enrolled and for Stage 2 of Part B, which has 8 patients now enrolled. Recruitment is tracking better than projected for the expansion cohort of Part A and as originally projected for Stage 2 of Part B. Immutep expects to report further interim data for TACTI-002 in calendar year 2021 or early calendar year 2022. 

INSIGHT 
INSIGHT is an investigator-initiated phase I trial investigating different combination treatments with efti and a different route of administration for efti. INSIGHT consists of 5 different arms from stratums A to E. 

INSIGHT-005 – combination with bintrafusp-alpha - new 
Immutep signed a collaboration and supply agreement with Merck KGaA, Darmstadt, Germany for a new stratum in 12 patients with solid tumours, known as Stratum E or INSIGHT-005. The trial will be run as an amendment to the protocol of the ongoing INSIGHT trial as the fifth arm and will evaluate efti in combination with Merck KGaA’s and GlaxoSmithKline’s bintrafusp alfa. The first patient is expected to be enrolled in H2 of calendar year 2021. 

INSIGHT-004 – combination with avelumab- final data 
At ASCO 2021, Immutep also reported encouraging final data from its INSIGHT-004 arm (stratum D). Promising activity signals were demonstrated from the combination of efti and avelumab, with a response rate of 41.7 percent in patients with different solid tumours. In addition, deep and durable responses were seen in patients with low or no PD-L1 expression and in indications such as gastroesophageal and cervical cancer which typically do not respond to immune checkpoint therapy. Importantly, the combination therapy showed a good safety profile. 

INSIGHT-003 – triple combination - new 
INSIGHT-003 is a new stratum in up to 20 patients with various solid tumours, also referred to as Stratum C. This is Immutep’s first evaluation of efti in a triple combination therapy of efti, chemotherapy and anti-PD-1 therapy. All regulatory and ethical approvals have already been received, enabling patient recruitment to commence. The first patient is expected to be enrolled in Q3 of calendar year 2021, with first interim results expected in 2022. 

The results of INSIGHT-003 are expected to inform a potential Phase II evaluating efti as part of a triple combination therapy along with an anti-PD-1 therapy and a chemotherapy, potentially in NSCLC. 

EAT COVID - Phase II clinical trial - ongoing 
The randomised portion of the investigator-initiated EAT COVID study is progressing at the University Hospital Pilsen in the Czech Republic. It is evaluating efti in up to 110 hospitalised patients with COVID-19.
 

Preclinical Pipeline
Immutep continues to work on GMP manufacturing preparations for IMP761 and is planning for toxicology studies and other pre-clinical evaluations. 

In addition, under a collaboration project commenced in 2019 with Cardiff University, Immutep has advanced the discovery and development of a potential new generation of small molecule anti-LAG-3 therapies. The project aims to make an oral treatment available to cancer patients and at a lower cost compared with the current anti-LAG-3 antibodies being developed by several other companies. 

Partnerships 
Immutep’s licensing and collaboration partnerships with Labcorp, GSK, Novartis, EOC Pharma and CYTLIMIC continue to progress. 

Intellectual Property 
Immutep was granted three new patents during the quarter, further expanding the company’s global patent estate. The European Patent Office granted a patent directed to combination therapy with leramilimab (LAG525), Immutep’s IMP701 antibody which is out-licensed to Novartis AG, and also a new divisional patent for efti in combination with a PD-1 or PD-L1 inhibitor. In addition, the Chinese Patent Office granted a new patent for efti in combination with chemotherapy, building on corresponding Australian, European, Japanese and United States patents. 

Financial Summary - Q4 FY21 
Cash receipts from customers for the quarter was USD 10k, compared to USD 59k in Q3 of FY 2021 (i.e. the quarter ended 31 March 2021). 

The net cash used in G&A activities in the quarter was USD 409k compared to USD 242k in Q3. The increase compared with last quarter is mainly related to capital raising related activities. Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter includes USD 128k in payment of Non-Executive Director’s fees and Executive Director’s salary. 

The net cash used in Research and Development activities in the quarter was USD 5.45 million, compared to USD 1.74 million in Q3. The significant increase is mainly due to the payment of upfront costs for the TACTI-003 clinical trial in Q4. Cash flow used in R&D activities for FY2021 was USD 12.47 million compared to USD 19.87 million for FY 2020. The decline of cash used in R&D activities in FY 2021 compared with FY 2020 is mainly due to the declining AIPAC expenses since patients in the AIPAC Phase IIb clinical trial have completed the treatment and moved into the follow-up phase and due to more material expenses related to the Phase IIb TACTI-003 clinical trial only starting to become payable during Q4 FY 2021. Total net cash outflows used in operating activities in the quarter was USD 5.71 million. In comparison, total net cash outflows from operating activities in Q3 was $3.05 million. 

Immutep received a AUD 1,155,055 cash rebate from the Australian Federal Government’s R&D tax incentive program during the quarter. 

In June 2021, Immutep secured commitments for USD 60 million via a two-tranche institutional placement which was supported by multiple institutional investors in Australia and offshore. 
The Company’s cash and cash equivalent balance as at 30 June 2021 was USD 60.59 million compared to a balance of USD 51.7 million as at 31 March 2021. This includes USD 13.7m from the first tranche of the institutional placement and USD 605k from the exercise of US warrants over American Depository Shares. 
A further USD 46.3 million will be raised from the second tranche of the placement conditional on shareholder approval at the Company’s Extraordinary General Meeting on 26 July 2021. 
In addition, Immutep is seeking to raise a further approx USD 5 million from eligible shareholders via a Share Purchase Plan (SPP), which closes on Monday, 19th July 2021 at 5pm (Sydney, Australia time). 

A copy of the Appendix 4C - Quarterly Cash Flow Report for the quarter can be requested from the contact details at the top of the release. 

About Immutep 
Immutep is a globally active biotechnology company that is a leader in the development of LAG-3 related immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value to shareholders. Immutep is listed on the Australian Securities Exchange (IMM), and on the 
NASDAQ (IMMP) in the United States. 
Immutep’s current lead product candidate is eftilagimod alpha (“efti” or “IMP321”), a soluble LAG-3 fusion protein (LAG-3Ig), which is a first-in-class antigen presenting cell (APC) activator being explored in cancer and infectious disease. Immutep is also developing an agonist of LAG-3 (IMP761) for autoimmune disease. Additional LAG-3 products, including antibodies for immune response modulation, are being developed by Immutep’s large pharmaceutical partners. 
Further information can be found on the Company’s website www.immutep.com.