Immutep Issues Newsletter Update to Shareholders

SYDNEY, Australia, Aug. 17, 2020 (GLOBE NEWSWIRE) -- Immutep Limited (IMMIMMP ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune disease, issued a newsletter to update its shareholders from Executive Director and Chief Executive Officer Marc Voigt, which is available below, and a formatted version is available on the Company's website (click here).

Dear shareholders,

I hope that this newsletter finds you and your families safe and well.

All of us have been affected in some way by the current pandemic and it appears that the pandemic and global economic consequences are far from being over.

However, what I have found uplifting during this time is the global community and scientific response to the coronavirus pandemic. A renewed humanitarian motivation has prompted biotech and pharma companies, as well as academia from around the world, to contribute to a potential cure or treatment. In the frontline of fighting the disease have been the doctors and nurses in all the different affected countries. We all owe them so much for their tireless work.

For me and the whole Immutep team, the pandemic has served as a reminder that we have an important role to play to improve the lives of patients, albeit cancer and autoimmune disease patients. It further motivates us to continue our efforts to develop LAG-3 technologies for patients and explore other potential areas, such as infectious disease where we feel efti could benefit patients by boosting their immune systems.

Celebrating 30 Years of LAG-3!

Did you know that the first paper identifying and describing the LAG-3 immune checkpoint was published in May 1990; as such, we recently marked its 30th anniversary!

The paper, entitled "LAG-3, a Novel Lymphocyte Activation Gene Closely Related to CD4" was written by Immutep's CMO and CSO Prof Frédéric Triebel who pioneered LAG-3's discovery, along with his col- leagues at the Institut Gustave-Roussy in Paris, France. The paper was published in the peer-reviewed Journal of Experimental Medicine, a journal that has achieved a high Impact Factor in 2018 of 10.9, placing it in the top 2% of scientific journals by Impact Factor.

Since then, the literature and innovation around LAG- 3 has accelerated substantially, with 784 papers now published worldwide.¹ Of these papers, 42 have been written by Prof Triebel and coworkers demonstrating his leadership in this emerging immunotherapy field.

Coincidentally, the first paper identifying and describing the PD-1 immune checkpoint was also published in the 1990s. MSD's KEYTRUDA® (pembrolizumab) became the first PD-1 inhibitor to receive approval for patients with advanced or unresectable melanoma on September 4, 2014.²

Now in 2020, KEYTRUDA is approved for use in many other cancer indications³ and, in 2019, KEYTRUDA generated approximately US$11 billion in revenues for MSD4. This is particularly encouraging for us given the data generated to date from combining our lead product candidate, eftilagimod alpha ("efti") with KEYTRUDA in our TACTI-mel and TACTI-002 clinical trials.

Great scientific and drug discoveries are often the result of many years, if not decades of hard work!

LAG-3 Landscape

Immutep is proud to be the worldwide leader in developing LAG-3 therapeutics, contributing four product candidates which are being evaluated in 13 clinical trials and almost 2,000 patients across the globe.

In addition, we have the only agonist LAG-3 products (efti and IMP761) being developed in the oncology and autoimmune fields.

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/7578d2fd-cfa7-4abe-8384-a868d214e347

Bristol Myers Squibb, the American pharmaceutical company, is also advancing rapidly in the LAG-3 space. It is expected to present data later this year or early next year from its Phase III clinical trials of relatlimab, a monoclonal antibody designed for the treatment of melanoma. If the results are positive, it would signal the validation of the whole LAG-3 space, along with its first product.

The LAG-3 opportunity & market size

Immutep is focused on developing LAG-3 therapies for:

• The global oncology drugs market which is expected to reach an estimated $176.5 billion by 2025, registering a compound annual growth rate (CAGR) of 7.6% from 2018 to 2025 .⁵
• The global autoimmune treatment market which is expected to grow at a CAGR of 4.34% between 2018 and 2025 to reach US$149.4 billion by 2025 .⁶

In addition, there is an opportunity to explore the use of Immutep's product candidates for the global infectious diseases market which is expected to reach US$86.2 billion by 2025 and has a CAGR of 6.6% during 2018 – 2025. Accordingly, Immutep is well positioned with exposure to three very large and growing pharmaceutical markets.⁷

Immutep has previously tested efti in clinical research in infectious disease, including in influenza and hepatitis vaccine studies.8 These studies showed that efti activates the body's innate immunity and, as a consequence, boosts adaptive immunity.

Immutep also has two patent families drawn to the use of efti in the treatment of infectious disease. For example, we announced the grant of a Japanese patent in September 2017 and the grant of a European patent in November 2018 with relevant claims in this field.

While Immutep remains firmly focused on developing its product candidates for the oncology and autoimmune disease markets, we were approached by an investigator with an interest in funding and conducting a trial in COVID-19, as noted in our Investor Presentation released on 29 April 2020. These discussions are continuing but are not yet consummated, as the investigator is seeking the necessary approvals, including the relevant Competent Authority approval. We appreciate that investors are anxious to hear of any further developments and we will, of course, update the market as soon as we are in a position to provide further details.

In general, infectious diseases present an attractive opportunity for Immutep to consider, not least because of the team's previous experience in the field and the current global humanitarian efforts to find a treatment for COVID-19. However, we remain focused and excited about our progress in oncology with efti and autoimmune diseases with IMP761, along with the progress being made by our partners with our out-licensed candidates.

Recent Immunotherapy Deal Activity

Immunotherapy continues to attract strong interest from big pharma, with multiple deals announced in June 2020. CSL paid US$450 million upfront for a Phase III haemophilia asset from uniQure. Gilead invested US$275 million for a 49.9% share in immuno-oncology biotech Pionyr Immunotherapeutics and has the option to buy the balance of the outstanding shares, valuing the business at US$1.5 billion - the key assets being two preclinical myeloid tuning assets which can help predict checkpoint inhibitor responsiveness.

Lastly, Sosei inked a discovery collaboration and licensing deal with AbbVie for novel therapies that modulate G protein-coupled receptor (GPCR) targets with an initial focus on inflammatory and autoimmune diseases. AbbVie is paying Sosei $32 million in upfront and near-term milestone payments.

Financing Update

In April, we raised A$12 million via a placement with new and existing institutional and sophisticated investors to support the development of our LAG-3 related clinical programs in immuno-oncology and autoimmune disease. We welcomed seven new institutions to our register through the Placement which extended our cash runway to the end of calendar year 2021.

Our cash position was further bolstered in May 2020 as we received a €2,173,454 (~ A$3,630,000) research and development (R&D) tax incentive payment in cash from the French Government under its Crédit d'Impôt Recherche scheme. We also received ~A$1.4 million in June 2020 from the Australian R&D tax incentive scheme.

Industry Conferences and Poster Presentations

Scientific conferences have taken on a virtual format since the COVID-19 pandemic and it has been good to be part of the industry's determination to push ahead with scientific innovation despite the challenges. The world needs new medicines now more than ever.

Immutep was pleased to announce new data at the American Society of Clinical Oncology's (ASCO) Annual Meeting 2020 via two poster presentations at the end of May. ASCO is the leading global scientific meeting for oncology professionals and represents an important platform at which industry participants present clinical results.

At ASCO, we presented new and improving interim data from our ongoing Phase II TACTI-002 study which we are conducting in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The poster can be viewed on Immutep's website (click here)

Immutep also presented first interim results from our ongoing INSIGHT-004 Phase I clinical trial at ASCO 2020. INSIGHT-004 is the fourth arm of the investigator-initiated INSIGHT trial being conducted by the Institute of Clinical Cancer Research at Krankenhaus Nordwest in Frankfurt (IKF). It is being conducted under Immutep's collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The poster can be viewed on Immutep's website (click here).

The new data presented at ASCO is also summarized in the Operational Snapshot section of this newsletter. You can also listen to a webcast of the results presented at ASCO (click here).

Immutep was also selected to present interim data from TACTI-002 via a poster short talk presentation as part of the high-impact paper presentation program at the American Association for Cancer Research (AACR) Virtual Annual Meeting held in a virtual format in April. You can also listen to an audio presentation of the AACR poster here. Interim results from CYTLIMIC's YCP02 phase I study, were also presented at AACR – see the Operational Snapshot.

Earlier interim data from TACTI-002 was also presented at the 34th German Cancer Congress which was held in Berlin, Germany in February. A webcast of the February results is available here.

Another key industry conference for business development attended by Immutep was BIO, held virtually in June 2020. Immutep and efti attracted much interest at the digital conference with the team attending multiple virtual one to one meetings, along with panel discussions and interactive sessions.

Operational Snapshot

AIPAC – Phase IIb study in breast cancer

In March, Immutep reported supportive initial efficacy data including Progression-Free Survival (PFS) and Overall Response Rate (ORR) from its Phase IIb AIPAC trial evaluating efti in combination with chemotherapy in patients with HER2-negative / hormone receptor positive metastatic breast cancer. Efti provided an improvement for patients' PFS compared to the placebo group at the 6-month landmark and an increased ORR of 48.3% compared to 38.4% in the placebo group. Encouraging results were reported in multiple predefined patient subgroups which represent a meaningful percentage of patients. Overall Survival (OS) and immune monitoring results are expected to be reported by the end of calendar year 2020. Further analysis of the subgroup data, the anticipated OS and immune monitoring data, and accompanying interactions with regulatory authorities and our partners, will inform our next steps.

It is not unusual for a new cancer therapy to be more effective in certain patient subgroups and less effective in other subgroups, and so we look forward to keeping investors informed of our strategy as more data comes to hand and we have further interactions.

We also note that the encouraging subgroup data, taken with the positive data we have seen to date in the TACTI-mel, TACTI-002, INSIGHT and INSIGHT-004 trials, is all supportive of the mode of action of efti - an antigen presenting cell activator that "pushes the gas" on the body's immune response.

TACTI-002 – Phase II study in solid cancers
Commercial Rights/Partner: Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada)

At this year's ASCO 2020 virtual event, Immutep announced new and improving data from TACTI-002. This included the first Complete Response from a patient with 2nd line head and neck squamous cell carcinoma (HNSCC), an improving Overall Response Rate in the same group (HNSCC), increasing  to 38.9% (previously 33%) and an improving Progression Free Survival (PFS) estimate of more than 9 months in patients with 1st line non-small cell lung cancer (NSCLC). This built on previous data sets that we reported in April, February and January 2020. We expect to report further data throughout 2020.

INSIGHT-004 – Phase I trial in advanced solid cancers
Commercial Rights/Partners: Pfizer and Merck KGaA

In April, enrollment was completed for our INSIGHT-004 Phase I clinical trial and we reported first data at ASCO in May. This first data included encouraging early efficacy signals in a variety of cancer indications. Overall, 33% of patients showed a Partial Response to the combination therapy of efti and avelumab which continues to be safe and well tolerated. Further data is expected to be reported throughout 2020.

TACTI-mel – Phase I trial in melanoma

Preparations are continuing for the clinical study report for our TACTI-mel trial in patients with metastatic melanoma. This trial reported positive final efficacy data in late 2019, including deep and durable responses to the combination of efti and pembrolizumab. 12 patients (50%) reported a decrease of ≥ 75% in the target lesions and 9 patients (38%) were treated for ≥12 months.

CYTLIMIC – Phase I in solid tumours
Commercial Rights/Partners: CYTLIMIC Inc.

Earlier this year, CYTLIMIC reported positive results from its YNP01 phase I clinical trial which is evaluating the combination immunotherapy of a HSP70 derived peptide, a GPC3 derived peptide, Immutep's IMP321 (efti) and Hiltonol in patients with advanced or metastatic solid cancer. The results showed that approximately 70% of patients showed an immune response to each peptide and were published in the scientific peer-reviewed journal, Cancer Immunology, Immunotherapy.

In addition, interim results from CYTLIMIC's YCP02 phase I study in hepatocarcinoma patients treated by a similar vaccine in a neoadjuvant setting before surgery, were presented at AACR2020 virtual meeting, showing a high degree of CD8 T cell infiltration in surgical specimens induced by the peptide vaccine compared to specimens from unvaccinated patients. This CD8 T cell influx at the tumor site could be seen as a direct proof of concept for the efficacy of the vaccine adjuvanted with efti and Hiltonol. In the trial, patients were treated with CYT001, a peptide vaccine that includes Immutep's lead product candidate, efti. CYTLIMIC reported tumor cell death and infiltration of T cells into tumor regions were observed in 6 out of 9 patients.

EOC Pharma – EFTI
Commercial Rights/Partner: EOC Pharma
In March, EOC Pharma completed patient recruitment for its ongoing Phase I EOC202A1101 study in China, which is evaluating efti in patients with metastatic breast cancer. EOC Pharma also confirmed its plans to continue advancing efti (designated as EOC202 in China) following its analysis of the Progression Free Survival (PFS) data, including subgroup analysis, from Immutep's phase IIb AIPAC study.

IMP761 – Preclinical studies in autoimmune disease

We announced in April that Batavia Biosciences, our manufacturing partner for IMP761, has made significant progress in cell line development, delivering a pharmaceutical-grade, stable CHO cell line that produces significantly high product yields of IMP761. The program is now focused on the preparations for the Good Manufacturing Practice (GMP) process compliance phase, before moving to clinical testing.

Novartis – LAG525
Commercial Rights/Partner: Novartis

Novartis currently has five clinical trials ongoing for LAG525 in multiple cancer indications for over 1,100 patients.

GSK – GSK'781
Commercial Rights/Partner: GSK

GSK's ongoing Phase II clinical study is evaluating GSK'781 in ulcerative colitis and clinical Proof-of-Concept is expected H1 2021.

OUTLOOK

Throughout 2020, Immutep has continued to build a strong pool of data supporting the efficacy of efti in multiple cancer indications. We have committed partnerships in place with five of the world's largest pharmaceutical companies: Merck, Pfizer, Merck MSD, Novartis and GSK, plus our partner in China, EOC Pharma. Not only does this validate our technologies, but it also demonstrates our strong track record of developing our assets. We have a strong pipeline of news flow ahead, including reporting further clinical trial results from our Phase II TACTI-002 study of efti. In addition, we'll be announcing regulatory progress and updates from our partnered programs.

Regards,

Marc Voigt
Executive Director and Chief Executive Officer
Immutep Limited

Footers:

1. https://pubmed.ncbi.nlm.nih.gov/?term=LAG-3&filter=years.1990-2020&timeline=expanded
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778665/
3. Refer https://www.keytruda.com/ for details of the cancer indications where Keytruda is approved for use.
4. https://investors.merck.com/news/press-release-details/2020/Merck-Announces-Fourth-Quarter-and-Full-Year-2019-Financial-Results/default.aspx
5. https://www.prnewswire.com/news-releases/oncologycancer-drugs-market-to-reach-176-50-bn-globally-by-2025-at-7-6-cagr-allied-market-research-300937810.html
6. https://www.prnewswire.com/news-releases/the-global-autoimmune-disease-therapeutics-market-size-is-expected-to-reach-149-4-billion-by-2025--rising-at-a-market-growth-of-4-34-cagr-during-the-forecast-period-300902336.html and www.kbvresearch.com/autoimmune-disease-therapeutics-market/   
7. Grand View Research: Infectious Disease Therapeutics Market Worth $86.2 Billion By 2025, published 2017. Infectious Disease Therapeutics Market Analysis By Disease Type (HIV infection, Influenza, Malaria, Tuberculosis, Hepatitis, and HPV infection), By Region, And Segment Forecasts, 2018 – 2025. Grand View Research. 2017.
8. Brignone C, Grygar C, Marcu M, et al. IMP321 (sLAG-3) safety and T cell response potentiation using an influenza vaccine as a model antigen: a single-blind phase I study. Vaccine. 2007;25:4641-50 and Brignone C, Grygar C, Marcu M, et al. IMP321 (sLAG-3), an immunopotentiator for T cell responses against a HBsAg antigen in healthy adults: a single blind randomised controlled phase I study. J Immune Based Ther Vaccines. 2007;5:5.

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 protein (LAG-3Ig) based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a chemoimmunotherapy for metastatic breast cancer termed AIPAC (clinicaltrials.gov identifier NCT02614833); a Phase II clinical trial being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada) referred to as TACTI-002 to evaluate a combination of efti with KEYTRUDA® (pembrolizumab) in several different solid tumours (clinicaltrials.gov identifier NCT03625323); a Phase I clinical trial being conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. referred to as INSIGHT-004 to evaluate a combination of efti with avelumab (clinical trials.gov identifier NCT03252938); and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel (clinicaltrials.gov identifier NCT02676869).

Additional LAG-3 products, including antibodies, for immune response modulation in autoimmunity and cancer are being developed by Immutep's large pharmaceutical partners. Immutep is also developing an agonist of LAG-3 (IMP761) for autoimmune disease.

Further information can be found on the Company's website www.immutep.com or by contacting:

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

U.S. Media:
Tim McCarthy, LifeSci Advisors
+1 (212) 915.2564; tim@lifesciadvisors.com