Immutep Quarterly Activities Report Q4 FY24

Rhea-AI Summary

Immutep (ASX: IMM; NASDAQ: IMMP) reported significant developments in Q4 FY24:

Key highlights:

• Entered a pivotal Phase III trial collaboration with MSD for eftilagimod alfa in 1L NSCLC
• Reported positive results from TACTI-003 Phase IIb trial in 1L HNSCC
• Presented encouraging data from AIPAC-003 and EFTISARC-NEO trials
• Signed an exclusive license with Cardiff University for oral LAG-3 therapy
• Completed A$100.2 million equity financing

Immutep's cash position totaled A$181.8 million, extending runway to end of 2026. The company continues to advance its clinical programs for efti in various cancer indications and IMP761 for autoimmune diseases.

Positive

• Entered third and most important clinical trial collaboration with MSD for Phase III NSCLC trial
• Positive results from TACTI-003 Phase IIb trial in 1L HNSCC, with ORR exceeding KEYTRUDA monotherapy
• Encouraging efficacy and safety data from AIPAC-003 trial in metastatic breast cancer
• Positive regulatory feedback received for TACTI-004 Phase III trial
• Exclusive license agreement signed with Cardiff University for oral LAG-3 therapy
• Completed A$100.2 million equity financing
• Strong cash position of A$181.8 million, extending runway to end of 2026

Negative

• Increased net cash used in G&A activities to $1.9 million in Q4 FY24, up from $0.7 million in Q3 FY24

Financial Analyst

Immutep's Q4 FY24 report reveals significant progress in its clinical programs and financial position. The company's A$100.2 million equity financing has extended its cash runway to the end of 2026, with a robust A$181.8 million in cash and term deposits. This financial cushion provides ample resources for advancing its pivotal Phase III TACTI-004 trial in first-line non-small cell lung cancer (NSCLC).

The collaboration with MSD for the TACTI-004 trial is a major milestone, potentially addressing the entire 1L NSCLC market eligible for anti-PD-1 therapy. This partnership, along with positive regulatory feedback from AEMPS and FDA, strengthens Immutep's position in the competitive oncology landscape.

Financially, the company's net cash used in R&D activities decreased to A$3.8 million from A$6.9 million in the previous quarter, indicating efficient resource allocation. The total net cash outflows used in operating activities also reduced to A$7.4 million from A$9.0 million, suggesting improved operational efficiency.

However, investors should note the increase in G&A expenses to A$1.9 million from A$0.7 million, primarily due to prepayment of annual costs. This is a common practice and shouldn't raise concerns if it's a one-time occurrence.

The company's strategic investment in a A$20 million bank term deposit demonstrates prudent cash management, balancing liquidity with potential returns. Overall, Immutep's financial position appears solid, providing a strong foundation for its ambitious clinical programs.

Oncology Research Analyst

Immutep's Q4 FY24 report showcases promising advancements in its efti development program across multiple cancer types. The TACTI-003 Phase IIb trial in first-line head and neck squamous cell carcinoma (1L HNSCC) yielded particularly impressive results. The combination of efti with KEYTRUDA showed an overall response rate (ORR) of ~34% across all PD-L1 expression levels, outperforming KEYTRUDA monotherapy in several subgroups.

Notably, in patients with high PD-L1 expression (CPS ≥20), the combination achieved a 31.0% ORR and 75.9% disease control rate (DCR), compared to 18.5% ORR and 59.3% DCR for KEYTRUDA alone. Even more striking is the 35.5% response rate in PD-L1 negative patients (CPS <1), significantly higher than the historical 5.4% ORR for anti-PD-1 monotherapy.

The AIPAC-003 trial in metastatic breast cancer also shows promise, with a 50% ORR and 100% DCR in the safety lead-in phase. The complete response in a heavily pretreated triple-negative breast cancer patient is particularly encouraging.

The EFTISARC-NEO trial's initial data in soft tissue sarcoma is intriguing, with 4 out of 6 patients (67%) showing near-complete pathological responses to the triple combination of efti, radiotherapy and KEYTRUDA. This high response rate in a typically difficult-to-treat cancer type warrants close attention.

These results collectively suggest that efti could potentially enhance the efficacy of existing immunotherapies across various cancer types and PD-L1 expression levels, potentially addressing current treatment gaps. However, larger confirmatory trials will be important to validate these early findings.

Biotechnology Industry Analyst

Immutep's Q4 FY24 report highlights significant strides in both clinical development and strategic partnerships. The collaboration with MSD for the TACTI-004 Phase III trial in 1L NSCLC is a major coup, potentially positioning efti as a key player in one of oncology's largest markets. This agreement, being Immutep's third and most important collaboration with MSD, underscores the growing industry confidence in efti's potential.

The company's expanding pipeline is noteworthy. Beyond efti, Immutep is advancing IMP761 for autoimmune diseases, with a first-in-human study set to begin in Q3 CY2024. The exclusive license agreement with Cardiff University for small molecule anti-LAG-3 therapies further diversifies Immutep's portfolio, potentially leading to more cost-effective, orally available treatments.

Immutep's intellectual property position has been strengthened with three new patents granted during the quarter. These patents protect key aspects of efti's manufacturing process and combination therapies, enhancing the company's competitive moat.

The A$100.2 million equity financing, which was oversubscribed, demonstrates strong investor confidence in Immutep's strategy and potential. The introduction of new institutional investors to the register could provide additional stability and support for future capital needs.

However, investors should be aware of the increasing complexity of Immutep's pipeline and the associated risks. Managing multiple clinical trials across various indications and development stages will require careful resource allocation and strategic focus. The company's ability to successfully navigate these challenges will be important for long-term success in the highly competitive immuno-oncology field.

Media Release

• Entered into third and most important clinical trial collaboration and supply agreement to date with MSD to evaluate eftilagimod alfa (efti) in combination with KEYTRUDA® (pembrolizumab) and chemotherapy for first-line non-small cell lung cancer in a pivotal Phase III trial
• Continuing positive clinical data reported from efti:
  • Positive results from TACTI-003 Phase IIb trial in first-line head and neck squamous cell carcinoma with efti in combination with KEYTRUDA®
  • Encouraging efficacy and safety data from AIPAC-003 Phase II/III trial with efti and paclitaxel in metastatic breast cancer presented at ESMO Breast Cancer 2024
  • Novel triple combination of efti with radiotherapy and KEYTRUDA well tolerated with encouraging initial efficacy data in EFTISARC-NEO Phase II trial in soft tissue sarcoma
• Positive regulatory feedback received from Spanish Agency for Medicines and Health Products (AEMPS) Competent Authority regarding the upcoming TACTI-004 Phase III trial
• Appointed Centre for Human Drug Research (CHDR) to conduct Phase I trial to evaluate IMP761, a first-in-class LAG-3 agonist antibody designed to treat autoimmune diseases
• Exclusive license agreement signed with Cardiff University for development of an orally available, small molecule anti-LAG-3 therapy to treat cancer
• A$100.2 million equity underwritten financing completed
• Immutep cash runway extended to the end of calendar year 2026, with a strong cash, cash equivalent and term deposit position totalling approximately A$181.8 million

SYDNEY, AUSTRALIA, July 31, 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 its activities for the quarter ended 30 June 2024 (Q4 FY24).

EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-004 (KEYNOTE-PNC91) – 1L NSCLC Phase III Clinical Collaboration with MSD
In June, Immutep entered into a clinical trial collaboration and supply agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA), through a subsidiary, to evaluate efti in combination with MSD’s anti-PD-1 therapy, KEYTRUDA and chemotherapy for a pivotal Phase III trial in first-line treatment of metastatic non-small cell lung cancer (1L NSCLC). The agreement marks the third and most important collaboration between Immutep and MSD for efti.

The TACTI-004 Phase III trial will enrol approximately 750 patients regardless of PD-L1 expression to address the entire 1L NSCLC market eligible for anti-PD-1 therapy, one of the largest markets in oncology. Under the collaboration, Immutep will conduct the registrational TACTI-004 Phase III trial and MSD will supply KEYTRUDA. Importantly, Immutep retains commercial rights to efti.

In other trials, efti in combination with KEYTRUDA with or without chemotherapy has generated compelling efficacy and favourable safety in 1L NSCLC, across all levels of PD-L1 expression.

During the quarter, Immutep also received positive feedback from the Spanish Agency for Medicines and Health Products (AEMPS) Competent Authority regarding TACTI-004. Following the end of the quarter, Immutep reported that it had received positive feedback from the US Food and Drug Administration (FDA) regarding the planned TACTI-004 trial. This positive feedback concluded the Company’s regulatory preparations for the trial design.

TACTI-003 (KEYNOTE-PNC34) – Phase IIb clinical trial in 1L HNSCC
During the quarter, Immutep reported positive topline results from the TACTI-003 Phase IIb trial in first-line head and neck squamous cell carcinoma (1L HNSCC). Efti in combination with KEYTRUDA (pembrolizumab) in 1L HNSCC led to overall response rates that exceed KEYTRUDA monotherapy across all levels of PD-L1 expression. In the overall evaluable TACTI-003 patient population (Cohorts A and B), the objective response rate (ORR) for efti in combination with KEYTRUDA was ~34% regardless of HPV status and PD-L1 expression, including patients with negative PD-L1 expression.

In the randomized controlled Cohort A, comprised of 1L HNSCC patients with any PD-L1 expression (CPS >1), the combination showed the strongest performance in patients with high PD-L1 expression (CPS ≥20) with an ORR of 31.0% and 75.9% disease control rate (DCR) in evaluable patients (N=29) as compared to a 18.5% ORR and 59.3% DCR for KEYTRUDA monotherapy in evaluable patients (N=27). In patients with low PD-L1 expression (CPS 1-19), the IO combination achieved an ORR of 34.5% in evaluable patients (N=29) as compared to a 33.3% ORR for KEYTRUDA monotherapy in evaluable patients (N=33), which is higher than historical published data for anti-PD-1 monotherapy including a 14.5% ORR in patients with CPS 1-19 in a registrational study¹. The large difference of the control arm versus historical results in low PD-L1 patients may be explained by imbalances between the TACTI-003 treatment groups.

In Cohort B, comprised of patients with negative PD-L1 expression (CPS <1), efti in combination with KEYTRUDA achieved a 35.5% response rate in evaluable patients (N=31). This response rate is among the highest recorded for a treatment approach not containing chemotherapy in patients with CPS <1 and compares favourably to a historical control of 5.4% ORR from anti-PD-1 monotherapy.¹ Additionally, the IO combination attained a high complete response rate of 9.7% (3 of 31 patients), which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1.¹ This efficacy and safety data from Cohort B was announced and presented by Dr. Robert Metcalf during an oral presentation at the ESMO Virtual Plenary session following the quarter end and represented a substantial improvement on preliminary Cohort B data Immutep reported in April 2024.

Based on the encouraging results from both Cohorts and high unmet medical need, the path forward in 1L HNSCC will be discussed with regulatory agencies. Efti has previously received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression. Immutep expects to present additional clinical data from TACTI-003 in H2 CY2024.

TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in 1L NSCLC
Immutep continues to follow patients with first-line non-small cell lung cancer (1L NSCLC), Part A of the TACTI-002 trial, where excellent median Overall Survival (mOS) rates were seen across all levels of PD-L1 expression. Immutep has previously reported final data from the other parts of the TACTI-002 trial.

AIPAC-003 – Integrated Phase II/III trial in MBC
Immutep reported encouraging efficacy, safety, and pharmacodynamic data from the safety lead-in phase of the AIPAC-003 Phase II/III trial at European Society for Medical Oncology (ESMO) Breast Cancer 2024 in May. This lead-in represents the first ever 90mg dosing of efti, given in combination with weekly paclitaxel. Positive efficacy results were reported in six metastatic breast cancer (MBC) patients including a confirmed 50% overall response rate (one complete response and two partial responses) and a 100% disease control rate.

The patient with a confirmed complete response (CR), who was diagnosed with triple-negative breast carcinoma (TNBC) in 2019 and failed multiple lines of therapy including a CDK 4/6 inhibitor for ER+/PR+ metastasis, started treatment in AIPAC-003 in May 2023. During treatment with efti and paclitaxel, this patient achieved a partial response that subsequently turned into a CR. As of the latest scan in mid-June, this patient’s ongoing CR has been maintained for over four months since stopping paclitaxel and being treated with efti monotherapy.

The efti and paclitaxel combination continues to be well tolerated with a favourable safety profile. Currently, 49 patients have been enrolled into the randomization phase. Further updates from AIPAC-003 will be provided in CY2024.

INSIGHT-003 – Phase I in non-squamous 1L NSCLC
The investigator-initiated INSIGHT-003 trial continued to enrol patients throughout the quarter, with 43 out of a target of 50 patients enrolled and safely dosed across six sites in Germany. INSIGHT-003 evaluates a triple combination therapy consisting of efti and an approved standard of care combination of chemotherapy (carboplatin and pemetrexed) and anti-PD-1 therapy (pembrolizumab) in patients as first line treatment in non-squamous NSCLC adenocarcinomas. Further updates from INSIGHT-003 will be provided in CY2024.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma
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. Currently, 2 out of a target of 30 patients have been enrolled.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma
Immutep announced initial encouraging data from EFTISARC-NEO, a Phase II investigator-initiated trial of efti in combination with radiotherapy, a standard-of-care treatment, plus KEYTRUDA for patients with soft tissue sarcoma (STS).

The triple combination has revealed no new safety findings and has been well tolerated in the first six patients who have completed the 10 weeks of treatment followed by surgery 2-3 weeks later. Initial efficacy data is very encouraging with 4 of 6 patients (67%) having near-complete pathological responses (the primary endpoint of the study). These deep responses are rarely seen in STS patients with standard therapeutic approaches including radiotherapy.

The EFTISARC-NEO study is the first to evaluate efti in a neoadjuvant setting, which takes place before intended surgery, and the first to combine efti with radiotherapy. Importantly, the neoadjuvant setting allows for the impact of this novel combination to be assessed in the tumour microenvironment.

Currently, 18 out of a target of 40 patients have been enrolled. Further clinical data from the EFTISARC-NEO trial is expected to be reported at a medical conference in H2 CY2024.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

In April, Immutep entered into an agreement with the Centre for Human Drug Research (CHDR), a world-class institute in Leiden, the Netherlands specialising in cutting-edge early-stage clinical drug research, to perform Immutep’s first-in-human clinical study of IMP761. As a proprietary LAG-3 agonist antibody, IMP761 has been designed to restore balance to the immune system by enhancing the “brake” function of LAG-3 and address the underlying cause of many autoimmune diseases. CHDR will utilise its unique challenge model that enables insights into IMP761’s pharmacological activity early in clinical development.

The trial is expected to enrol its first participants during Q3 CY2024.

PARTNERS

Cardiff University
In June, Immutep entered into an exclusive License Agreement with Cardiff University granting the Company exclusive rights to develop and commercialise anti-LAG-3 small molecules, which represent the next generation of anti-LAG-3 therapies. The Agreement builds on many years of collaborative work between Immutep and the expert team at Cardiff University.

Immutep’s program aims to develop an orally available small molecule anti-LAG-3 treatment for cancer patients at a lower cost compared with the anti-LAG-3 monoclonal and bi-specific antibodies that are commercially available or under clinical development today.

A number of promising compounds that block LAG-3 have been identified in collaboration with the world-leading scientists at Cardiff University.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted three new patents. A new divisional patent was granted by the European Patent Office protecting Immutep’s combination preparations comprising efti and a chemotherapy agent, which is either a platinum-based anti-neoplastic agent or a topoisomerase I inhibitor.

The Canadian and Indian Patent Office each granted a new patent protecting Immutep’s intellectual property for a binding assay for determining MHC Class II binding activity. The assay is used in the characterisation of efti in GMP-grade manufacturing.

CORPORATE & FINANCIAL SUMMARY

Fully Underwritten Financing
Immutep raised a total of approximately A$100.2 million during the quarter via an Institutional Placement (approximately A$72.0 million) together with an Institutional Entitlement Offer (A$17.6 million) and a Retail Entitlement Offer (A$10.6 million). The Placement attracted strong demand from existing institutional shareholders of the Company, and also introduced several new institutional investors to the Immutep register. In addition, the Institutional Entitlement Offer had strong support with a take-up rate from eligible institutional investors of approximately 100%.

The new funds will be used predominantly to advance Immutep’s pivotal Phase III TACTI-004 trial in first-line non-small cell lung cancer and to fund manufacturing, working capital and Offer costs.

Cash Flow Summary
During the quarter, Immutep continued to fund the advancement of its clinical trial programs for efti and preclinical program for IMP761 to create value for shareholders. The Company is well funded with a strong cash and cash equivalent balance as at 30 June 2024 of approximately A$161.8 million. In addition to this cash balance, Immutep has an A$20 million bank term deposit, which has been recognised as a short-term investment due to the maturity date of 6-12 months. This aggregate position of A$181.8 million as at 30 June 2024 gives Immutep an expected cash reach to the end of CY2026.

Cash receipts from customers in Q4 FY24 were $14k, which was the same as for Q3 FY24. The net cash used in G&A activities in the quarter was $1.9 million, compared to $0.7 million in Q3 FY24. The increase is mainly due to prepayment of certain annual G&A costs. Payments to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $300k.

The net cash used in R&D activities in the quarter was $3.8 million, compared to $6.9 million to Q3 FY24. Payment for staff costs was $2.0 million in the quarter which was consistent with the last quarter.

Total net cash outflows used in operating activities in the quarter were $7.4 million compared to $9.0 million in Q3 FY24.

For the cash flow used in investing activities, the company invested $20 million in bank term deposit with maturity between 6 and 12 months which has been recognised as a short-term investment.

The Company completed a capital raising of approximately $100.2m in June 2024 and paid capital raising costs of $4.6 million in the quarter. Net cash inflow from financing activities for the quarter was approximately $95.7 million.

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, Sodali & Co
+61 (0)406 759 268; catherine.strong@sodali.com

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

¹ Burtness, B. et al. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. Journal of Clinical Oncology 2022 40:21, 2321-2332. Note, the 5.4% ORR is calculated from the 37 evaluable patients with CPS <1.

FAQ

What is the status of Immutep's TACTI-004 Phase III trial for NSCLC?

Immutep entered a clinical trial collaboration with MSD for TACTI-004, a Phase III trial evaluating eftilagimod alfa with KEYTRUDA and chemotherapy in first-line NSCLC. The trial will enroll approximately 750 patients regardless of PD-L1 expression.

What were the results of Immutep's TACTI-003 Phase IIb trial in HNSCC?

The TACTI-003 trial showed positive results, with eftilagimod alfa in combination with KEYTRUDA achieving overall response rates exceeding KEYTRUDA monotherapy across all PD-L1 expression levels in first-line HNSCC patients.

How much funding did Immutep (IMMP) raise in their recent financing?

Immutep raised approximately A$100.2 million through an Institutional Placement and Entitlement Offer in Q4 FY24.

What is Immutep's (IMMP) current cash position as of June 30, 2024?

As of June 30, 2024, Immutep had a cash and cash equivalent balance of approximately A$161.8 million, plus an additional A$20 million in a bank term deposit, totaling A$181.8 million.

What new partnership did Immutep (IMMP) announce for LAG-3 therapy development?

Immutep entered an exclusive License Agreement with Cardiff University to develop and commercialize orally available anti-LAG-3 small molecules for cancer treatment.