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Bicycle Therapeutics Announces Presentation of Additional Human Radiopharmaceutical Imaging Data for MT1-MMP at the American Association for Cancer Research Annual Meeting 2025

On April 29, 2025 Bicycle Therapeutics plc (NASDAQ: BCYC), a biopharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported the presentation of additional human imaging data that validate the potential of MT1-MMP, a tumor antigen overexpressed in many cancers, as a novel target for cancer treatment and demonstrate the positive properties of Bicycle Radioconjugates (BRC) for radiopharmaceutical imaging (Press release, Bicycle Therapeutics, APR 29, 2025, View Source [SID1234652303]). The data will be presented today during a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago.

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"The additional imaging data using an early BRC molecule continue to validate the potential of MT1-MMP as a novel cancer target, demonstrate the translatability of our preclinical data and position our technology for use as potential radiopharmaceutical therapies," said Michael Skynner, Ph.D., chief technology officer of Bicycle Therapeutics. "The new imaging data from the second patient with breast and bladder cancer presented today build on what was previously demonstrated in the first patient with advanced lung cancer, and we are encouraged that these data represent what we have seen so far in 12 patients with various solid tumors. We continue to advance our radiopharmaceuticals pipeline and look forward to sharing additional updates in the future, including initial human imaging data for our second target EphA2 later this year and the start of our first company-sponsored clinical radiopharmaceutical trials next year."

AACR 2025 Data Highlights

The German Cancer Consortium (DKTK), part of a cooperative network with the German Cancer Research Center (DKFZ), will present human imaging data conducted with an early BRC molecule targeting MT1-MMP. Imaging was performed in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of non-small cell lung cancer, and an 84-year-old female diagnosed with invasive ductal breast cancer and high-grade urothelial (bladder) cancer.

The 65-year-old male patient with advanced pulmonary adenocarcinoma underwent fluorine-18-labelled FDG-PET/CT imaging and two weeks later underwent MT1-MMP-PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer. As presented at a previous medical meeting, the MT1-MMP-PET scan demonstrated BRC tracer uptake in the primary tumor in the lung and in the lymph nodes and bones where the cancer had spread, corroborating the findings of the FDG-PET scan. While MT1-MMP-PET imaging demonstrated lower BRC tracer uptake in the primary tumor compared to FDG-PET imaging [maximum standardized uptake value (SUVmax) 6.0 g/mL vs. 10.3 g/mL], MT1-MMP-PET BRC tracer uptake was comparable in lymph node metastases (SUVmax 4.7 g/mL vs. 4.4 g/mL) and higher in bone metastases (SUVmax 7.9 g/mL vs. 6.0 g/mL).

The 84-year-old female patient with invasive ductal breast cancer and high-grade urothelial cancer underwent contrast-enhanced CT imaging and later underwent MT1-MMP-PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer. The MT1-MMP-PET scan revealed higher BRC tracer uptake in the primary tumors in the breast (SUVmax 4.5 g/mL) and the bladder (SUVmax 6.6 g/mL) compared to contrast-enhanced CT imaging. The MT1-MMP-PET scan also showed the cancer spread to the lymph nodes, lower spine (sacral bone) and skull, and detected a mass in the adrenal gland above the left kidney. Surgery confirmed the patient had bladder cancer that spread to the lymph nodes, and immunohistochemistry (IHC) testing confirmed MT1-MMP expression in the tumor cells.

These data are representative of the results seen in 12 out of 14 patients with various cancers, including those affecting the lung, head and neck, and bladder, who have undergone MT1-MMP-PET imaging to date. Imaging was unsuccessful or inconclusive in two patients. Overall, the results demonstrate the rapid distribution of the BRC tracer throughout the body, high uptake of the BRC tracer in the primary tumor(s) and/or in metastases where the cancer spread in the body, and elimination through the kidneys. Scans showing retention in the kidneys were in line with expectations given the imaging was conducted using a pathfinder non-optimized BRC imaging agent. Additional and more detailed analyses of the data and confirmation of MT1-MMP expression in the tumors via IHC are ongoing.

The poster presentation, "Development and clinical translation of phage display derived MT1-MMP-specific bicyclic peptide for radiotheranostic applications," is available in the Publications section of the Bicycle Therapeutics website.

Aulos Bioscience Presents New Phase 2 Data for AU-007 Demonstrating Continued Strong Anti-Tumor Activity in Advanced Cancers at AACR Annual Meeting

On April 29, 2025 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of its lead immune-activating antibody therapeutic, reported positive results from its Phase 1/2 dose escalation and cohort expansion study of its investigational candidate AU-007 (Press release, Aulos Bioscience, APR 29, 2025, View Source [SID1234652302]). The data were shared in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois.

The interim Phase 2 data demonstrate clear evidence of durable partial and complete tumor response in multiple cancer types, including patients with melanoma whose tumors had progressed through prior checkpoint inhibitors and who received a combination of AU-007 and low-dose, subcutaneous aldesleukin. Durable tumor shrinkages were also observed in patients with checkpoint inhibitor-resistant or progressed renal cell carcinoma (RCC) who received the same AU-007 and aldesleukin regimen. Additionally, AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the interleukin-2 (IL-2) class, with regulatory T cells (Tregs) decreasing and CD8 effector T cells expanding at all AU-007 dose levels.

"We are very pleased with the clinical activity observed with AU-007 and low-dose, subcutaneous aldesleukin without a checkpoint inhibitor, as it accentuates our confidence in AU-007 as a potential best-in-class therapeutic for multiple cancers," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "Deep and durable tumor shrinkages, including complete responses, are occurring in patients who were refractory to treatment and had achieved no responses from highly potent prior immuno-oncology regimens. Importantly, the results reinforce the previously reported observation that the CD8 effector T cell expansion and Treg reduction correlates with clinical efficacy. This key driver of Treg reduction coupled with CD8 effector T cell expansion and enhancement of the CD8/Treg ratio differentiates AU-007 from other IL-2 therapeutic programs. Today’s data support further evaluation of AU-007 and low-dose, subcutaneous aldesleukin as a second-line treatment for melanoma, where limited treatment options exist. Our new Phase 2 cohort augmenting this regimen with anti-PD-1 nivolumab is now enrolling patients and we look forward to presenting preliminary data later this year."

Key findings from interim results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 95 patients as of the data cutoff date of March 20, 2025, are as follows:

Continued tolerable and manageable safety profile was observed with AU-007 as a monotherapy and in combination with low-dose, subcutaneous aldesleukin at all doses evaluated in Phase 1 dose escalation.

No dose-limiting toxicity occurred throughout Phase 1 dose escalation.
Most drug-related adverse events were mild and transient Grade 1 or 2 events.
The most common treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin were Grade 1 or 2 fatigue (21%), pyrexia (21%), chills (19%) and infusion-related reaction (15%).
The incidence of Grade 3 or 4 treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin was cytokine release syndrome (1%), lymphopenia (8%) and anemia (3%). All events were transient and resolved, and there were no Grade 5 treatment-related adverse events.
Durable objective responses were observed in patients with multiple tumor types enrolled in the Phase 1 dose escalation and Phase 2 cohorts.

One patient with metastatic bladder cancer that progressed on an anti-PD-L1 treatment was treated with AU-007 every two weeks (Q2W) and one loading dose of low-dose, subcutaneous aldesleukin, has an ongoing metabolic complete response and continues on treatment for two years.
One patient with metastatic nasopharyngeal head and neck cancer that progressed on five prior systemic therapies received AU-007 and low-dose, subcutaneous aldesleukin Q2W. This patient experienced an unconfirmed complete response after 20 months and continues on treatment.
Three patients with melanoma refractory to either prior anti-CTLA-4 and anti-PD-1 or anti-PD-1 and anti-LAG-3 therapy were treated with AU-007 Q2W and one loading dose of low-dose, subcutaneous aldesleukin, and experienced deep and durable tumor shrinkages of 100% (complete response in all target lesions, continues on study for 13+ months), 58% (continues on study for 10+ months) and 48% (on study for 13 months).
One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 and one loading dose of low-dose, subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control.
The regimen of AU-007 and low-dose, subcutaneous aldesleukin exhibits distinct pharmacodynamic effects in the class and continues to drive durable decreases in Tregs, increases in CD8 T cells, and corresponding increases in CD8/Treg ratios.

A decrease in Tregs appears to be a critical determinant of observed efficacy, with Tregs decreasing in the periphery in the presence of AU-007 at all dose levels.
This finding supports AU-007’s overall mechanism of action to control and redirect endogenously produced IL-2 and exogenously administered IL-2 to reduce the Treg population and increase circulating CD8 effector T cell populations. Treg cells are highly immunosuppressive cells that can blunt the immune response to tumors and reduce the durability of responses and progression-free survival.
The Phase 2 expansion cohorts evaluating AU-007 and a single loading dose of low-dose, subcutaneous aldesleukin continue to enroll patients with advanced cutaneous melanoma who have failed prior checkpoint inhibitor therapy as well as patients with PD-L1+ non-small cell lung cancer (NSCLC) who have failed prior checkpoint inhibitor therapy.

An additional Phase 2 cohort is evaluating AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor with ADCC effector function; anti-PD-L1) in PD-L1+ NSCLC in patients who have failed prior checkpoint inhibitor therapy. As announced earlier this month, a new Phase 2 cohort evaluating AU-007 and a single subcutaneous loading dose of low-dose aldesleukin combined with nivolumab (checkpoint inhibitor; anti-PD-1) as a second-line treatment for cutaneous melanoma is enrolling patients who have not received a prior BRAF/MEK inhibitor. Aulos anticipates presenting preliminary clinical data from these two Phase 2 expansion cohorts in the second half of 2025.

The poster, "AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update," (Abstract CT178) is accessible to meeting registrants as an electronic poster on the AACR (Free AACR Whitepaper) 2025 virtual meeting platform. It is also available on the Aulos Bioscience website in the Abstracts and Publications section.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

Artios Pharma Reports Differentiated Clinical Activity in STELLA Phase 1/2a Study for Lead Program ART0380 at the American Association for Cancer Research (AACR) Annual Meeting 2025

On April 29, 2025 Artios Pharma Limited ("Artios"), a clinical-stage biotech company led by pioneers of DNA damage response ("DDR") drug development, reported encouraging data from its ongoing STELLA Phase 1/2a trial (NCT04657068) in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, Artios Pharma, APR 29, 2025, View Source [SID1234652301]). The presentation by Principal Investigator Susanna Ulahannan, MD, Associate Professor, Stephenson Cancer Center at the University of Oklahoma and Director, Drug Development, Sarah Cannon Research Institute (SCRI) at OU Health Stephenson Cancer Center, highlighted the Phase 1/2a clinical data from the STELLA trial of Artios’ lead candidate, ART0380, in combination with low-dose irinotecan in advanced or metastatic solid tumors.

Artios is pursuing a differentiated clinical development path with its lead product candidate, ART0380, which selectively targets a protein kinase called Ataxia telangiectasia and Rad3-related (ATR). ATR plays a key role in the cellular response to replication stress, a process that can occur endogenously or exogenously, for example via chemotherapy. Many cancers exhibit high endogenous replication stress, such as Ataxia-Telangiectasia Mutated (ATM) protein deficiency found in up to 24% of high-unmet need solid tumors. Artios’ innovative approach exploits replication stress to kill cancer cells through triple targeting: selecting cancers with high replication stress, inducing further replication stress with a low dose of irinotecan, and preventing cellular rescue by inhibiting ATR with ART0380.

"Artios is exploiting a new area of DNA damage response called replication stress with ART0380, and the data from our Phase 1/2a study shows robust clinical activity and good tolerability in a large, identifiable patient population," said Ian Smith, Chief Medical Officer of Artios. "These are unprecedented data for the ATR inhibitor class, and they validate our unique approach of combining ART0380 with a low dose of irinotecan to amplify replication stress. We are encouraged by the incidence and durability of the responses in ATM-deficient cancers, including those of particularly high unmet need, such as pancreatic and colorectal cancer."

Summary of Key Clinical Results:

Artios completed patient enrollment in the dose escalation and initial expansion. As of the data cut-off in February 2025, 87 patients with advanced/metastatic solid tumors who had no satisfactory alternative therapy available to them were treated with ART0380 in combination with low-dose irinotecan, of which 58 patients were treated at the RP2D (recommended Phase 2 dose). These patients’ tumors had varying levels of ATM protein.

The combination treatment at the RP2D showed a meaningful duration of response and prolonged clinical benefit across multiple histologies
37% confirmed overall response rate (cORR) in patients with ATM-negative1 and ATM-low1 cancers (14/38), according to RECIST
50% cORR in ATM-negative cancers (10/20) with a median duration of response (mDoR) of 5.7 months (several responses ongoing)
22% cORR in ATM-low cancers (4/18) with the median duration of response not reached
Responses were observed in 8 different solid tumor types
The combination had a favorable safety profile, was well tolerated, and was shown to be suitable for long-term dosing

The 21-day combination treatment regimen at the RP2D includes administering ART0380 (200mg) on days 1 – 3 and 8 – 10, and irinotecan (60mg/m²) on days 1 and 8.

"The first results from the ongoing STELLA clinical trial are compelling and demonstrate the potential for ART0380-irinotecan combination treatment in ATM biomarker-driven tumors. I am encouraged by the clinical activity and durable responses across multiple cancer indications in heavily pretreated patients, especially considering the complete responses observed in metastatic pancreatic cancer," added Susanna Ulahannan, MD, Director, Drug Development, SCRI at OU Health Stephenson Cancer Center, USA.

The Phase 1/2a trial for ART0380 is conducted with SCRI’s contract research organization, SCRI Development Innovations. Based on the meaningful clinical responses observed, Artios is initiating expansion studies in earlier-line settings, including colorectal and pancreatic cancers, to enable pivotal development of ART0380.

About ART0380

ART0380 is an orally administered, selective small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR) with first- and best-in-class potential. ATR is activated as the cell’s response to replication stress frequently occurring in rapidly multiplying cells. Inhibiting ATR with ART0380 removes a cancer cell’s ability to repair damaged DNA, leading to the killing of cancerous cells. ART0380 is designed to maximize the therapeutic window and is optimized for combination with DNA damaging therapy to improve patient outcomes. It is currently being evaluated in multiple clinical settings to identify its potential in high replication stress tumors. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was discovered as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.

Quanterix and Akoya Biosciences Announce Amended Merger Agreement

On April 29, 2025 Quanterix Corporation (NASDAQ: QTRX), a company fueling scientific discovery through ultra-sensitive biomarker detection, and Akoya Biosciences (NASDAQ: AKYA), The Spatial Biology Company, reported an amendment to the terms of their previously announced merger agreement (Press release, Akoya Biosciences, APR 29, 2025, View Source [SID1234652300]).

Under the amended terms, Quanterix will issue approximately 7.76 million shares of its common stock and pay $20 million in cash to Akoya shareholders. Each Akoya share will receive $0.38 per share in cash and 0.1461 shares of Quanterix common stock.

With the amended exchange ratio, Quanterix will issue over 9 million fewer shares than under the original deal terms. Quanterix shareholders will own approximately 84% of the combined company and Akoya shareholders will own approximately 16%.

Masoud Toloue, PhD, Chief Executive Officer of Quanterix, said, "The strategic merits of the transaction remain strong even as the market has been focused on academic funding and tariff concerns. In light of recent volatility, we re-engaged with Akoya to revise the terms of the agreement. The combined company will provide a significant value creation opportunity for shareholders."

Brian McKelligon, Chief Executive Officer of Akoya, said, "We remain excited to combine with Quanterix and believe this partnership offers compelling value for Akoya shareholders. We look forward to closing the transaction and leveraging our collective scale to drive synergies across our organizations and customers, expediting our path to profitability."

Additional Details about the Transaction

The revised transaction terms and amended merger agreement have been approved by the Quanterix Board and the Akoya Board, respectively.

Shareholders of Akoya who hold more than 50% of Akoya’s common stock have agreed to vote in favor of the merger on the amended terms.

As a result of the amended merger agreement, Quanterix will no longer hold its previously announced special meeting of shareholders.

The transaction is expected to close during the second quarter of 2025, subject to the approval of Akoya shareholders and satisfaction of other customary closing conditions.

An updated investor presentation is being furnished by Quanterix to the Securities and Exchange Commission and also is available at View Source, highlighting the benefits of the combination.

Advisors

Goldman Sachs & Co. LLC is serving as financial advisor to Quanterix with Covington & Burling LLP and Sidley Austin LLP serving as legal counsel. Perella Weinberg Partners LP is serving as financial advisor to Akoya and DLA Piper LLP is serving as legal counsel.

Immutep Quarterly Activities Report & Appendix 4C Q1 FY25

On April 29, 2025 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, reported an update on its activities for the quarter ended 31 December 2024 (Q2 FY25) (Press release, Immutep, APR 29, 2025, View Source;v=7bc42bd11d853ed5e8c28f2ffcd6a069ee5cd6b4 [SID1234652261]).

EFTI DEVELOPMENT PROGRAM FOR CANCERTACTI-004 –Start of Phase III Trial in 1L NSCLC

In December 2024, Immutep initiated its pivotal TACTI-004 Phase III clinical trial of eftilagimod alfa ("efti") for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC). The receipt of regulatory approval from the Australian Therapeutic Goods Administration means that Immutep has transitioned into a Phase III company; a significant milestone for the Company.

Immutep has successfully completed regulatory submissions in the vast majority of the more than 25 countries that will be part of the global TACTI-004 trial. Additional approvals from multiple countries are expected in the weeks and months ahead. The Company expects to enrol the first patient in Q1 of CY2025.

TACTI-003 (KEYNOTE-C34) –Phase IIb Trial in 1L HNSCC

In December 2024, Immutep reported further positive results from Cohort B of the TACTI-003 (KEYNOTE-C34) Phase IIb trial. Cohort B is evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrentor metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with PD-L1 negative tumours (CPS <1) who typically do not respond well to anti-PD-1 therapy alone. The results were presented by Martin Forster, M.D., Ph.D., at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress 2024.

Adding to the high response rates and favourable safety data previously reported in July 2024, the new data showed that, encouragingly, median overall survival (OS) has not yet been reached and the 12-month OS rate is 67%. A promising progression-free survival (PFS) of 5.8 months, interim median duration of response (DOR) of 9.3 months, 35.5% objective response rate (ORR) and 58.1% disease control rate (DCR) were also reported. The complete response rate increased to 12.9% and 16.1%, according to RECIST 1.1and iRECIST, respectively. This data compares favourably to historical results from anti-PD-1 therapy alone in 1L HNSCC patients with CPS <1. In addition, efti in combination with KEYTRUDA continues to be well-tolerated with no new safety signals. Immutepwill continue to follow the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward.

AIPAC-003 –Phase II/III Trial in Metastatic Breast Cancer

In October 2024, Immutep completed patient enrolment in the Phase II portion of the AIPAC-003 trial. The randomised Phase II portion of the trial enrolled 65 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Patients across 22 clinical sites in Europe and the United States have been randomised 1:1 to receive either 30mg or 90mg dosing of efti in combination with paclitaxel to determine the optimal biological dose consistent with the FDA’s Project Optimus initiative and prior regulatory interaction with FDA. Data cleaning and analysis is ongoing.

INSIGHT-003 –Phase I Trial in Non-Squamous 1L NSCLC

In November 2024, first overall survival results were reported from the investigator-initiated INSIGHT-003 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).

Mature data from patients with a minimum follow-up of 22 months (N=21) demonstrated results significantly exceeding historical controls and expectations. Data included a median OS of 32.9 months, median PFS of 12.7 months, and a 24-month OS rate of 81.0%. Data from all evaluable patients to date (N=40) showed a marked improvement in ORR compared to historical controls. Safety remains favourablewith no new safety signals reported.

Subsequent to quarter end, patient enrolment was completed for INSIGHT-003 in January 2025. The trial reached its enrolment target of approximately 50 evaluable patients across multiple clinical sites in Germany led by the Frankfurt Institute of Clinical Cancer Research IKF. Additional data updates are expected in 2025 and beyond.

EFTISARC-NEO –Phase II Trial in Soft Tissue Sarcoma

Also in November, new data from the EFTISARC-NEO Phase II investigator-initiated trial of efti in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS) were presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting.

Based on preliminary analysis, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS. The combination achieved a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgery as compared to a historical median of 15% from radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosis rate has also been identified as a predictor of overall survival for STS patients in the neoadjuvant setting.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. Additionally, the triple combination therapy is safe with no grade ≥3 toxicities related to efti and KEYTRUDA.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

IMP761 is a first-in-class agonist LAG-3 antibody designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases.

In December 2024, Immutep reported favourable initial safety data from the placebo-controlled, double-blind first-in-human Phase I study evaluating IMP761. There have been no treatment related adverse events in the first three of five single ascending dosecohorts in healthy participants. Additional safety data and assessment of pharmacokinetic/pharmacodynamic (PK/PD) relationships to follow in the first half of CY2025.

PARTNER ACTIVITY

Collaboration with Monash University

In December 2024, new findings that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans, were published in Science Immunology. The work by Monash University and Immutep, is also the first to show the crystal structure of a human LAG-3/MHC-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted threenew patents for eftiandIMP761 in various territories. In particular, Immutep was granted a new patent for efti in combination with a PD-1 pathway inhibitor for the treatment of infection from the Brazilian Patent Officeand a new patent for the same combination for the treatment of cancer or infection by the Japan Patent Office. In addition, a new patent was granted for IMP761 by the Malaysian Patent Office.

CORPORATE & FINANCIAL SUMMARY

Board & Senior Management Changes

Independent Non-Executive Director, Anne Anderson, tendered her resignation from the role, effective from 4 October 2024. The Board thanked her for her contribution to Immutep and wished her every success with her next endeavours.

As Immutep’s efti program has advanced into Phase III development, the Company has continued to grow and evolve its team. As part of this, Christian Mueller, who has been with Immutep for over eight years, most recently as SVP Regulatory and Strategy has been promoted to Chief Development Officer. In addition, Dr Florian Vogl, Immutep’s Chief Medical Officer will depart the Company in April 2025. The Company’s current Medical Affairs Advisor, who has been working in different roles closely with Immutep for over nine years, Dr Stephan Winckels, has been appointed acting CMO and taken over all related responsibilities.

Cash Flow Summary

During the quarter, Immutep continued to advance its clinical trial programs for efti and for IMP761. The Company is well funded with a strong cash, cash equivalent and term deposit balance as at 31 December 2024 of approximately A$159.26 million in total, which gives Immutepan expected cash reach to the end of CY2026. The A$159.26 million total balance consists of: 1) a cash and cash equivalent balance of $73.89 million and 2) bank term deposits totalling A$85.37 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months.

In Q2 FY25, cash receipts from customers were $8k. The net cash used in G&A activities in the quarter was $566k, compared to $961k in Q1 FY25. Payments to Related Parties (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees andExecutive Directors’ remuneration of $344k.

The net cash used in R&D activities during the quarter was $16.2 million, compared to $9.5 million to Q1 FY25. The increase is mainly due to the increased level of clinical trial activities especially the commencement of the phase III TACTI-004 clinical trial. Paymentsfor staff costs were$2.5 million in the quarter compared to $2.8 million in Q1 FY25.

Total net cash outflows used in operating activities in the quarter were $19.0 million compared to $8.6 million in Q1 FY25.

Total cash flow used in investing activities for the quarter was $30.4 million, mainly due to the net increase of $30.0 million in short-term investments. The short-term investments are comprised of term deposits with maturities of greater than 3 months and less than 12 months. During the quarter, the company invested $35.3 million inshort-term investments and transferred back $5.3 million from short-term investments that had matured to cash at bank, resulting in anet increase in short-term investments of $30.0 million.