On July 31, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has concluded a license agreement with F. Hoffmann-La Roche Ltd (hereafter "Roche") [Head Office: Basel, Switzerland. Thomas Schinecker] for inavolisib, a PI3K alpha inhibitor, currently in development for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation in combination with palbociclib and fulvestrant (Press release, Chugai, JUL 31, 2024, View Source;category= [SID1234645178]). Under the license agreement between Roche and Chugai, Chugai obtained exclusive rights for the development and marketing of inavolisib in Japan. Roche will receive an upfront fee and milestone payments.

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"PIK3CA mutations are detected in approximately 40%1 of patients with hormone receptor (HR)-positive breast cancer. Patients with PIK3CA mutated HR-positive, HER2 negative advanced BC have a poorer prognosis and thus there remains a significant unmet need for this patient group. Inavolisib, which has shown positive data in global clinical trials, is expected to be a new treatment option for patients with breast cancer. Chugai will work closely with Roche to conduct domestic development in order to bring inavolisib to patients with breast cancer as soon as possible," said Chugai’s President and CEO, Dr. Osamu Okuda.

Inavolisib was discovered by Genentech, a member of the Roche Group, and is currently under development for two global Phase III clinical studies in patients with locally advanced or metastatic HR-positive/HER2-negative breast cancer with PIK3CA mutations (INAVO120 and INAVO121) and one global Phase III clinical study in patients with PIK3CA mutated HER2-positive breast cancer (INAVO122). The INAVO120 study demonstrated that the inavolisib-based regimen (in combination with palbociclib and fulvestrant) more than doubled progression-free survival, reducing the risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001) in the first-line setting. The inavolisib-based regimen has also been shown to be well tolerated with a manageable safety profile.
Based on the positive results of the INAVO120 study, inavolisib has been granted Breakthrough Therapy Designation for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA mutations in the first-line setting as well as Priority Review by the U.S. Food and Drug Administration (FDA) for the new drug application with a PDUFA date of November 27, 2024

Chugai will continue to effectively utilize the research and development resources of the Roche Group to find innovative new drugs so as to satisfy unmet medical needs.

About inavolisib
Inavolisib is an investigational, oral targeted treatment that could provide well-tolerated, durable disease control and potentially improved outcomes for people with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer. Inavolisib has been designed to help minimize the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.

About the INAVO120 study
The INAVO120 study is a global Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

The INAVO120 study met its primary endpoint, extending PFS by 7.7 months compared to the control group, demonstrating the superiority of the combination of inavolisib, palbociclib and fulvestrant (hazard ratio, 0.43 [95% CI = 0.32, 0.59]; p<0.0001)2. Regarding safety, the incidence of hyperglycemia, diarrhea, stomatitis, nausea, and skin rash was higher in the inavolisib group compared to the control group, but most of these events were Grade 1-2 (incidence of Grade 3-4 events was hyperglycemia: 5.6%, stomatitis: 5.6%, diarrhea: 3.7%, nausea: 0.6%, and skin rash: 0%), confirming that the inavolisib was well tolerated and the safety profile was manageable.

About Hormone Receptor-Positive Breast Cancer
HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70%3 of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

On July 31, 2024 Imugene Limited (ASX:IMU), a clinical-stage immuno‐ oncology company, reported its Quarterly Cash Flow report (Appendix 4C) for the quarter ended 30 June 2024 (Press release, Imugene, JUL 31, 2024, View Source [SID1234645177]).

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CLINICAL TRIAL UPDATES

Azer-cel continues to enrol in the Phase 1b study. Azer-Cel (azercabtagene zapreleucel) is an off-the-shelf (allogeneic) cell therapy which targets CD19 to treat blood cancers.

The Phase 1b allogeneic (allo) CAR T study is an ongoing multi-centre clinical trial in patients who suffer from a difficult to treat sub-set of non-Hodgkin’s lymphoma (NHL) called Diffuse-Large Bcell lymphoma (DLBCL) that have relapsed after autologous CAR T therapy. These DLBCL patients have limited therapeutic options and are an unmet medical need.

Following completion of the Phase 1b study there is potential to start a registrational Phase 2/3 study in 2025 and become the first approved allogeneic CAR T cell therapy for cancer. VAXINIA Bile Tract Cancer trial opened, and the VAXINIA MAST trial higher dose cohort opened for enrolment.

Imugene launched its Phase 1 bile tract cancer (cholangiocarcinoma) trial, which aims to enrol 10 patients. In the Phase 1 MAST trial, one patient with bile tract cancer who had failed three prior lines of therapy received a mid-dose of IT-administered monotherapy VAXINIA, achieved a complete response, meaning the disappearance of all signs of cancer in response to treatment, and the patient has been in the trial for over 630 days. A second patient with bile tract cancer (cholangiocarcinoma), who has also progressed on prior drug therapies, achieved stable disease, meaning their cancer neither increased nor decreased and no new tumours appeared for more than four months upon receiving IV administered VAXINIA.

The results seen in these patients provided the rationale for Imugene to open a VAXINIA trial in this specific patient population. The FDA granted Fast Track Designation to the VAXINIA program in November 2023, accelerating the development and potential approval process due to the urgent need for new treatments. The MAST trial, which began by administering low doses to patients with advanced solid tumours, has progressed through several dose escalation cohorts without safety concerns.

This bile tract cancer trial not only supports the ongoing evaluation of VAXINIA’s efficacy, but also emphasizes its role in addressing the significant challenges associated with treating bile tract cancer, an aggressive form cancer with limited effective treatments for patients. Subsequent to the end of the quarter, Imugene announced that the first patient had been dosed at St. Vincent’s Hospital in Melbourne.

Additionally, it was confirmed that the fifth cohort of both arms of the Phase 1 MAST monotherapy dose escalation trial have now cleared, with the sixth high dose cohort of each arm having opened.

Imugene Phase 1 onCARlytics trial doses first patient in Intravenous (IV) combination arm in the OASIS trial.

Late in the quarter, the first patient was dosed in the intravenous (IV) combination arm of the Company’s Phase 1 onCARlytics clinical trial. The trial, known as OASIS, is pioneering in its combination of a CD19-expressing oncolytic virus with a CD19-targeting drug called BLINCYTO (blinatumomab). CD19 is used in blood cancers, but solid cancers like breast, lung, gastric, bile tract, and colon, etc. don’t have a common target on their cell surface; the goal of onCARlytics is to present a target for CD19 therapies. The CD19-expressing CF33 oncolytic virus marks or paints the tumour target with CD19 on the cell surface, followed by treatment with a CD19 targeting therapy. The trial aims to recruit 40-45 patients with advanced solid tumours and is currently being conducted at three sites in the US, with the potential to expand to 10 sites.

The first patient, who has bile tract cancer, was dosed at City of Hope in California. The primary objective of the trial is to evaluate the safety and efficacy of onCARlytics when administered either intratumorally (IT) or intravenously (IV), alone or in combination with blinatumomab, a CD19-targeting bispecific monoclonal antibody.

Preliminary early combination data are expected in the fourth quarter of 2024, subject to patient enrolment rates. If successful, onCARlytics could significantly expand the market for CD19-targeting therapies. CD19 therapies are currently only approved in blood cancers, which only make up 10 percent of cancers, while solid cancers make up 90 percent of the cancer market. If successful onCARlytics could make CD19 targeted therapies an option to treat patients with solid cancers. This could potentially impact a market which is estimated to be valued at approximately US$532 billion by 2032.

CORPORATE UPDATES:

Imugene and Kincell Bio Announce Strategic Manufacturing and Process Development Partnership for azer-cel. In April, Imugene and Kincell Bio established a strategic partnership focused on manufacturing and process development. Under this agreement, Kincell Bio acquired Imugene’s manufacturing facility in North Carolina. Additionally, this strategic shift ensures continued clinical supply of azer-cel, Imugene’s advanced allogeneic CAR T cell therapy while Imugene retains all rights to azer-cel.

VAXINIA selected for Oral and Poster Presentations at 2024 Cholangiocarcinoma Foundation Annual Conference.

Imugene presented its VAXINIA technology at the 2024 Cholangiocarcinoma Foundation Annual Conference in April in Salt Lake City, Utah. In both an oral and a poster presentation, the company discussed the effectiveness and safety of VAXINIA as a treatment for gastrointestinal malignancies, including bile tract cancer (cholangiocarcinoma), highlighting its potential as a monotherapy treatment in a field where early detection and treatment options are limited. This conference provides a platform for healthcare professionals and researchers to exchange insights on advancing the treatment and understanding of bile tract cancer.

Presentation at Bell Potter Emerging Leaders Conference.

Imugene CEO & Managing Director Leslie Chong presented at the Bell Potter Emerging Leaders Conference in May 2024. A copy of the presentation can be viewed here.

FINANCIALS

At the end of the June quarter Imugene has A$93.1 million in cash or equivalents (Excluding R&D tax rebate of ~$11 million expected imminently), providing a runway to support its clinical pipeline and operations into late 2025. Net cash used in operating activities for the quarter amounted to A$19 million, with direct research and development costs accounting for 57% of total costs. In accordance with Listing Rule 4.7C, payments made to related parties and their associates included in items 6.1 of the Appendix 4C include payments for remuneration of director fees to executive and non-executive directors in the normal course of business at commercial rates, excluding reimbursements of out-ofpocket expenses. Options granted to directors that are included in Imugene’s Remuneration Report under share-based payments, are non-cash amounts and represent valuations using the Black-Scholes methodology. Share-based payments relating to option grants to directors are therefore not included in item 6.1 of the Appendix 4C.

On July 30, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new approaches for the treatment for cancer and fibrosis, reported further progress across its small molecule, focal adhesion kinase (FAK) inhibitor program and the release of its Appendix 4C Cash Flow Report (attached) for the quarter ending 30 June 2024 (Press release, Amplia Therapeutics, JUL 31, 2024, View Source [SID1234645176]).

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Key Highlights from the Quarter

• Updated data and analysis from the Phase 1b ACCENT trial in pancreatic cancer presented at the prestigious annual meetings of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).
• Recruitment in the ACCENT Phase 2a trial has progressed well and in early June we reported 24 of 26 patients had been recruited.
• The inaugural meeting of the Company’s Clinical Advisory Board was held.

Operations Update

Clinical Development

The strategic priority for the company over the last quarter has been timely execution of the Phase 2a portion of the ACCENT trial in pancreatic cancer. The ACCENT clinical trial explores the safety, tolerability, and most importantly, efficacy of the Company’s best-in-class FAK inhibitor narmafotinib, in combination with the chemotherapy drugs gemcitabine and Abraxane, in newly diagnosed patients with advanced pancreatic cancer.

The Company reported dosing the first patient in the Phase 2a ACCENT trial in January this year using the dose identified from the Phase 1b trial. In March 2024, the Company reported that 11 patients had been dosed in the Phase 2a trial at that time, and in June we reported that 24 patients of the 26 required had been recruited to the trial.

The Phase 2a stage of the ACCENT trial is open at six sites in Australia-in Melbourne, Sydney and Brisbane-and at five hospitals in the Republic of Korea, in and around the capital Seoul. Korea was chosen as a second country in which to conduct the trial given the excellent medical and clinical trial facilities and capabilities in the country.

The Phase 2a trial is being conducted using Simon’s Two-Stage Design, a commonly used method for Phase 2 clinical trials. The trial design was chosen as it can result in efficient determination of whether a new drug has sufficient promise to warrant further development. In the ACCENT trial, the first stage consists of efficacy assessment in a group of 26 patients where a confirmed complete or partial response in six (6) patients in considered sufficiently promising to warrant continuation of the trial. In the second stage of the trial an additional 24 patients will be enrolled, giving a total of 50 patients. The decision about the drug’s efficacy is made based on the combined results of both stages.

It is important to note that the formal term ‘confirmed partial response’ means that there is at least a 30% reduction in the overall size of tumour lesions, sustained over a two-month period, with no new tumour lesions. Given that the ACCENT trial is focused on patients with advanced pancreatic cancer, a >30% reduction in tumour size represents a significant therapeutic response in this aggressive disease. In the Phase 1b stage of the ACCENT trial completed in October last year, we reported that six out of the fourteen patients on the trial recorded a partial response.

In April we presented a poster with updated analysis of data from the ACCENT Phase 1b trial at the world’s foremost scientific meeting in cancer research, the annual meeting of the AACR (Free AACR Whitepaper). In addition to the excellent response rate observed for the fourteen patients on the trial, significantly higher than predicted from historical studies of gemcitabine and Abraxane treatment alone, we also presented data showing there was a clear dose-dependence in response, where four of the six partial responses observed were from the highest dosing cohort. This, combined with other data, strongly suggests that the responses observed are related to effects from the drug narmafotinib. This data was subsequently published in the abstracts for the annual ASCO (Free ASCO Whitepaper) meeting in May. During the conference, the inaugural meeting of the Company’s Clinical Advisory Board was also held to discuss the ACCENT trial progress, as well as strategy and plans for additional trials of narmafotinib in pancreatic cancer. The CAB consists of five world-class clinical oncologists, with expertise in pancreatic cancer from Australia, the US and Canada.

Financial update

Amplia finished the June 2024 quarter with cash of $4.8 million (March 2024: $3.4million). During the quarter, the Company had net operating cash outflows of $2.5 million in relation to operating activities (March 2024: $2.0 million outflow).

Operating cashflows included:

• Outflows of $0.7 million for staff and administration/corporate costs; and

• Outflows of $1.8 million for research and development costs, which primarily related to trial costs, Contract Research Organisation (CRO), manufacturing and other CMC related costs incurred in relation to the Phase 1b/2a clinical trial for narmafotinib (AMP945).

During the quarter the Company undertook a two for five, fully underwritten pro-rata nonrenounceable Entitlement offer and raised $4.27m (before costs) receiving significant support from new and existing institutional investors and the Company’s Directors.

Payments to Related Entities

In accordance with Listing Rule 4.7C, payments made to related parties and their associates included in item 6.1 of the Appendix 4C incorporates directors’ fees, salaries and superannuation. Total payments made for the quarter equals $112,500 and relate to paymentsto the CEO/Managing Director in line with employment contracts and payments to the Non-Executive Directors.

Outlook and future activities

The Company will continue to focus on timely execution of the Phase 2a portion of the ACCENT trial. Additional clinical opportunities for narmafotinib, including a potential clinical trial in ovarian cancer, are also being actively explored.

On July 31, 2024 Clinical stage drug development company Syntara Limited (ASX: SNT) reported that it has completed full recruitment in its Phase 2 trial evaluating SNT-5055, in combination with ruxolitinib, treating the bone marrow cancer myelofibrosis (Press release, Syntara, JUL 31, 2024, View Source;v=70bc033a22188bdfefb8a0b8ad3c24897ef2837d [SID1234645175]).

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After commencement of the open-label study in December 2023, Syntara has reached the milestone with the 15ᵗʰ patient dosed yesterday and has already exceeded the minimum threshold of one month treatment for 12 patients proposed in FDA discussions for safety evaluation.

The trial is being conducted across 19 clinical trial sites in the USA, Australia, South Korea and Taiwan. SNT-5505 is a pan-LOX inhibitor and the lead asset in Syntara’s proprietary clinical pipeline.

Syntara expects to report interim results from the trial in late 2024, in conjunction with the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In line with the excellent safety profile observed in earlier phase 1 and phase 2 studies, no drug related dropouts nor any serious adverse reactions have been observed to date.

The reassuring safety profile, alongside the interim data, is expected to allow Syntara to engage with and discuss pivotal study design with the FDA in Q1 2025, with the full 12month data set to be available in Q3 2025.

Syntara CEO Gary Phillips said:

"I’d like to thank the haematology clinics, investigators and the Syntara clinical team for achieving this significant milestone in such a timely fashion. We now look forward to presenting our interim data later in the year and building a solid foundation for the next stage of discussions with the FDA and potential strategic partners."

Syntara commenced the combination trial after it found encouraging efficacy and an excellent safety profile in a Phase 2 monotherapy trial of the drug, as presented at ASH (Free ASH Whitepaper) in December 2023. An effective pan-LOX inhibitor, such as SNT-5505, for myelofibrosis has disease modifying potential for patients and would unlock a market conservatively estimated to be more than $1 billion per annum.

SNT-5505 is a pan-LOX inhibitor that has also demonstrated compelling pre-clinical data when used in combination with standard of care in other haematological malignancies such as myelodysplastic syndrome and solid tumours like those found in hepatocellular carcinoma and pancreatic cancer.

On July 31, 2024 – 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 30 June 2024 (Q4 FY24) (Press release, Immutep, JUL 31, 2024, View Source [SID1234645174]).

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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 (Free ESMO Whitepaper) 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 TACTI002 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) (Free ESMO Whitepaper) Breast Cancer 2024 in May. Thislead-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 worldleading 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 (detailed in item 6.1 of the Appendix 4C) 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. A copy of the Appendix 4C-Quarterly Cash Flow Report for the quarter is attached.