FAQ

Frequently asked Questions.


General Information

Q1: Who is Immutep Limited?

We are a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune disease, with operations in Australia, Europe and the United States.

We are the global leaders in Lymphocyte Activation Gene-3 (“LAG-3”), a cell surface molecule which plays a vital role in regulating T cells. Our objective is to harness and strengthen the power of patients’ own immune systems.

We have one pre-clinical product candidate and three clinical stage product candidates. We also continue to assess new LAG-3 opportunities.

 

Q2: What are Immutep’s main product candidates?

Our lead product is eftilagimod alpha (efti, LAG-3Ig or IMP321), a first-in-class antigen presenting cell (APC) activator currently in a number of combination clinical trials, including for breast cancer, melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma (see Clinical Trials).

IMP731 is a depleting antibody intended to destroy LAG-3 expressing activated T cells involved in autoimmunity, being developed by partner GlaxoSmithKline (GSK).

IMP701 is an antagonist antibody targeting the LAG-3 molecule on T cells with potential applications in the treatment of cancer, under development by our partner Novartis.

Our newest product candidate, IMP761, is an antibody against highly active immune cells in autoimmune diseases, currently in preclinical development.  

Q3: When and where was Immutep founded?

Immutep, formerly Prima BioMed, was originally created as a mining company (Prima Resources) in Australia in 1987, and was first publicly traded in 1988 on the Australian Stock Exchange. The Company was repositioned as a biotechnology company in 2001 following the acquisition of the rights to develop technologies from the Austin Research Institute (now the Burnet Institute), including CVac™, an immunotherapeutic product candidate.

On 2 October 2014, Prima BioMed announced the acquisition of Immutep SA, a private French biotechnology company.

The transaction was formalised at the Annual General Meeting of shareholders on 14 November 2014 and completed on 17 December 2014. On 1 December 2017, Prima BioMed changed its name to Immutep Limited following shareholder approval at the Annual General Meeting on 17 November 2017.

Q4: Where is Immutep located?

Immutep’s corporate headquarters are in Sydney, Australia. Immutep also has operations in Germany, France and the United States.

Q5: Where is Immutep listed and what is an American Depositary Receipt (ADR)?

Immutep Limited (Immutep) is listed on the Australian Securities Exchange (ASX) under the ticker, IMM. The ASX is the home market of Immutep and the exchange on which its ordinary shares can be traded.

Immutep has a secondary listing on the NASDAQ under the ticker, IMMP. Immutep’s American Depositary Receipts (ADRs) can be traded on the NASDAQ.

For more information on ADRs please visit www.adrbnymellon.com/resources/dr-basics

Each ADR represents 10 Immutep Limited ordinary fully paid shares. For further details on Immutep’s ADRs please visit https://www.adrbnymellon.com/?cusip=45257L108

R&D

Q1: What is LAG-3?

LAG-3 stands for Lymphocyte Activation Gene-3 (LAG-3 or CD223), a protein which in humans is encoded by the LAG-3 gene. It is a cell surface molecule, which is involved in the regulation of T cells.

The LAG-3 protein controls the signaling between T cells and antigen presenting cells (APC’s). It has a unique dual mechanism of action, as an APC activator to stimulate the immune response and, in other applications, as a negative regulator of T cells to switch off the immune response.

Q2: What stage of development are the product candidates from Immutep at?

In total, we have one preclinical product candidate and three clinical product candidates.

Our lead product candidate eftilagimod alpha (efti) is under clinical development in a Phase IIb chemoimmunotherapy clinical trial in metastatic breast cancer and a Phase II clinical trial in combination with Keytruda in collaboration with Merck & Co (MSD) in non-small cell lung cancer and head and neck squamous cell carcinoma. In addition, efti is being evaluated in three Phase I trials, including a trial being conducted in collaboration with Merck (Germany) and Pfizer.

Our partnered product candidates include depleting and antagonist LAG-3 antibodies which are undergoing Phase II clinical trials. The newest product candidate IMP761 is under preclinical development.

Q3: Where is Immutep’s R&D performed?

We operate as a global company, and therefore, perform R&D in different countries. Clinical research is conducted in Australia, Europe and the United States, and we have a laboratory facility in Paris.

Q4: What is Immutep’s current development strategy?

Our current development strategy is to focus on our LAG-3 programs in order to bring our product candidates to commercialisation, either through our own clinical trials or through our various commercial partnerships. This requires ongoing funding and as a clinical stage biotechnology company we continually assess opportunities for supporting our product pipeline and R&D activities.

Q5: What partnerships or collaborations does Immutep have in place?

We are a globally active biotechnology company developing immunotherapeutic products for cancer and autoimmune diseases. Active collaborations are an integral part of our business and we have a number of collaborations underway with various corporations and academic institutions.

Our current product development pipeline includes partnerships and collaborations with five major pharmaceutical companies: Novartis, GSK, Merck & Co (MSD), Merck (Germany) and Pfizer. In addition, we are partnered with EOC Pharma (Eddingpharm) in China, have a clinical trial collaboration with CYTLIMIC in Japan, and have a research collaboration with Monash University in Australia.

Q6: What is Immutep’s patent position?

Immutep owns or co-owns a total of ten patent families covering its pipeline of product candidates. In particular, Immutep owns four families covering embodiments of eftilagimod alpha (efti or IMP321).  Three of these families are directed to methods of treating cancer and infectious disease with efti alone, or in combination with chemotherapy, a therapeutic antibody acting via ADCC or a PD-1 / PD-L1 inhibitor. A fourth family is directed to an assay associated with the manufacture of efti.

In addition, Immutep owns three patent families covering IMP761, and co-owns with Novartis two families covering IMP701. The two families covering IMP701 are exclusively licensed to Novartis. Immutep also co-owns a patent family covering IMP731. This family is co-owned with the National Institute for Health and Medical Research (INSERM) and has been exclusively licensed to GSK.

EFTI

Q1: How does efti work?
  • In AIPAC the combination therapy with efti was designed to boost the immune response against tumour cells compared to chemotherapy plus placebo.
  • Apoptotic tumour cells induced by chemotherapy release antigenic tumour debris which are then captured by APCs.
  • Boosting the APC network with efti increases cytotoxic T-cell responses which complements the direct cytotoxic effect of the chemotherapy.
Q2: What is efti?
  • Eftiagimod alpha, known as efti or IMP321, is a soluble LAG-3 protein targeting a subset of major histocompatibility complex class II (MHC class II) on antigen presenting cells. It is potentially synergistic with other therapeutic agents, e.g. immuno-oncology agents or chemotherapies.
Q3: How does efti work in combination with chemotherapy?
  • The combination of efti and chemotherapy amplifies the immune system response using the antigens released by dying tumour cells induced by chemotherapy.
  • The chemotherapy causes the so called “immunogenic” death of tumour cells which results in the release of tumour specific proteins (antigens). These antigens can be taken up by a specific type of immune cells (called antigen presenting cells) and presented to cytotoxic T cells leading to an immune response in the body against other cancer cells.

AIPAC CLINICAL RESULTS

Q1: What has Immutep reported from its AIPAC top-line data read-out?
  • Progression-free at 6-month landmark: 63% paclitaxel + efti vs 54% paclitaxel + placebo
  • Hazard Ratios (HR) in favour of efti:

o   0.93 for overall PFS;

o   0.61 for low monocyte count patients subgroup;

o   0.65 for more aggressive/immunogenic luminal B type patients subgroup; and

o   0.76 for lower general performance status patients subgroup.

  • Overall Response Rate (ORR): 48.3% efti vs 38.4% paclitaxel
Q2: What do these results mean for patients?
  • Overall AIPAC’s results didn’t indicate a strong clinical efficacy in HR-positive metastatic breast carcinoma, which is not a particularly immunogenic tumor.
  • However, it seems that there are significant subgroups where a benefit has been observed.
Q3: You have previously talked about the birth of a whole new class of immuno-oncology products. Have the results delivered that?
  • It is not yet clear how AIPAC will contribute to the class of APC activators as some important data like Overall Survival and immune monitoring is expected later in the year and the first data has not been fully analysed yet.
Q4: What are the next steps with regulators? What is your strategy?
  • We plan to engage in discussions with regulatory authorities regarding the AIPAC results.
  • We will carefully assess our strategic options and will take into account the very encouraging results in other trials, e.g. TACTI-002, as we move forward.
Q5: Have you had interest from pharma in out-licensing efti?
  • As you may be aware, Immutep already has collaborations in place with four of the world's top 10 pharmaceutical companies.
  • It is our duty to have a good and ongoing dialogue with the industry.
  • We will keep the market informed of any material developments.

COVID-19

Q1: Has Immutep been impacted by COVID-19?
  • We expect impacts from COVID-19 as we run trials in multiple countries and expect at least some hospitals to be affected by the pandemic. Obviously, this is something we are monitoring on a daily basis.
  • The health and safety of our team is our priority right now. Many of us are working remotely and are taking every precaution and guidance to protect our employees through this difficult period.
  • As a global company spanning multiple locations and time zones, our staff were already setup to work from home remotely and so we haven’t missed a beat.
  • Our manufacturing partner has confirmed that supply of efti had not been disrupted.
  • From a clinical perspective, we are in the fortunate position that AIPAC is now in the follow up phase.
  • Patient recruitment is well progressed for our other live trials, TACTI-002 and INSIGHT-004, but recruitment could, of course, be affected in the future.
  • One area where the whole industry is affected, including Immutep, is Conferences. However, the industry and Immutep will adapt and we will find other means of presenting our data to our peers.
Q2: Has manufacturing of efti been impacted?
  • Our CMO, Wuxi recently confirmed that manufacturing and supply of efti has not been impacted in any significant way.
  • Our current supply of efti is sufficient for all our ongoing clinical trials and are already warehoused outside of China in our central European warehouse.
Q3:The FDA and other regulators have issued guidance about how clinical trials need to be conducted in the current pandemic environment to protect patients. Will this hamper the recruitment of patient therapy for your ongoing TACTI-002 trial?
  • Firstly, we agree fully that patients must be protected through this time. Some of them are immunocompromised and it would not be good to expose them to any unnecessary risk.
  • Of course, the response from each of the hospitals of our clinical sites will vary depending on the degree to which their hospital and country has been impacted by the virus.
  • We will continue to monitor the situation and take appropriate action as necessary.
Q4: Will regulators be too distracted with COVID-19 to consider new drugs in oncology?
  • Obviously, responding to the pandemic is paramount for all of us, however, cancer is obviously a life-threatening disease with high unmet medical need.
  • Our engagement with regulators so far has been productive.
  • If anything changes, we will of course adapt and inform the relevant stakeholders.
Q5: Are your ongoing trials large enough to cope if a higher proportion of participating patients suffer SAE or death?
  • Protecting patients is incredibly important and we will make any and all adjustments to how we conduct our trials to protect them.
  • It is too early to say what the impact in terms of SAE and death might be.
Q6: Could COVID-19 skew the results of your ongoing clinical trials if patients become ill?
  • As a respiratory illness, it should be possible to separate the impact of COVID-19 from any disease progression resulting from cancer.
  • Our hope is to protect participating patients and also deliver a meaningful improvement in their health through the combination treatment, however, the final responsibility lies in the hand of the hospitals and physicians.
Q7: Could efti work for coronavirus?
  • As an immune booster, there is certainly the potential for it to be active against many infectious diseases, particularly for patients with a lower immune system status.

EAT COVID TRIAL

Q1: How could efti work in COVID-19 patients?
  • Through the EAT COVID trial, efti aims to boost a patient's immune response to prevent the patient from developing severe COVID-19 symptoms that require intensive care and can lead to respiratory failure and death.
  • As an antigen presenting cell (APC) activator, efti could empower the body's CD8+ T cells, giving them a 'licence to kill'. These CD8+ effector killer T cells are then able to detect and eliminate infected epithelial cells where the virus can replicate.
  • Following infection with the virus, helper COVID-19 specific CD4 T cells become activated and express CD40L and LAG. Then they help the two effector arms of the immune response, namely production of IgM and then IgG by B cells and the killer CD8 T cells, by conditioning the dendritic cells (the so called "professional" APC) through the CD40 and MHC II molecules expressed on APCs. APCs could also be conditioned directedly in the absence of any CD4 T cell help by "danger signals" expressed by the COVID-19 virus like the TLR3, TLR7 and TLR8 agonists. In fact, when the condition of the patient in ICU is worsening and the viral load is at its peak, these danger signals could lead to uncontrolled inflammation leading to death.
  • Efti being a soluble LAG-3 molecule and being non-inflammatory (compared to TLR agonists) provides the CD4 T cell help directly to the APCs in order to induce more COVID-19 specific CD8 T cells to become cytotoxic to eliminate the COVID-19 epithelial cell reservoirs. This is particularly important in the elderly where the CD8 T cell responses are weaker due to immuno-senescence.
  • To our knowledge, efti is currently the only APC activator of its kind being evaluated against COVID-19 in a randomised Phase II trial.
Q2: What prompted Immutep to think efti might help patients?
  • Immutep has previously tested efti in preclinical infectious disease research, including influenza and hepatitis vaccine studies.
  • These studies showed that efti activates the body's innate immunity and as a consequence, boosts adaptive immunity.
  • These preclinical results prompted Dr. Marek Nalos, Head Medical ICU at University Hospital Pilsen and the Nepean Hospital in Sydney, who was involved in preclinical infectious disease research with efti for a number of years, to ask Immutep to consider how efti could be applied to treat COVID-19 patients.
Q3: When could efti be approved for COVID-19 patients?
  • It's too early to say when it could be approved. As a Phase II trial, we will know more about efti's safety and efficacy as results are reported.
  • Initial interim results are expected to be reported from early 2021.
  • The data would inform plans for a future pivotal clinical trial.
Q4: How many people are in the trial and how are they selected?
  • The trial involves up to 110 adult patients who have been hospitalised with COVID-19 at University Hospital Pilsen.
  • The trial is a high-quality placebo controlled, 1:1 randomised, double blinded Phase II clinical trial.
  • Recruitment will start with a safety run-in of 6 patients and then a first cohort of 26 randomised patients.
  • Successive cohorts will be recruited following a positive recommendation from the Data Monitoring Committee based on initial safety and efficacy results.
Q5: How will you know if efti has worked?
  • Patients will receive 10 mg subcutaneous injections of efti on days 1, 3 and 7, in addition to standard care.
  • At day 15 the patient's clinical status is recorded, as per the WHO recommended evaluation scale to give the trial's primary endpoint.
Q6: Why is the trial taking place in Czech Republic?
  • Unfortunately, the health situation in the Czech Republic is extremely serious, prompting a renewed urgent need to evaluate potential treatments.
  • On 22 October 2020, the Czech Republic had the highest number of new infections in Europe, based on a rolling 7 day average. Per capita, the number of new infections is also one of the highest in the world and much worse than the United States, for example. That is, on 22 October 2020, 929 new infections per million residents were reported in the Czech Republic, based on a rolling 7 day average. This compares to 181 new infections per million residents in the United States, based on a rolling 7 day average. Or expressed differently, as of 22 October 2020, 26.8% of COVID-19 tests in the Czech Republic were positive compared with the United States where 6% of tests were positive, based on a rolling 7 day average.[1]
  • The Czech Republic reported 14,150 new cases and 106 deaths from COVID-19 on 22 October 2020 and there has been a rapid increase in the number of COVID-19 related hospitalisations and ICU admissions in recent days.[2] [3]

[1] Our World in Data: available from ourworldindata.org

[2] Worldometer: available from worldometer.info

[3] European CDC: available from https://covid19-country-overviews.ecdc.europa.eu/#3_eueea_and_the_uk