On October 31, 2023 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported the outcome of a protocol-defined interim analysis of data from the pivotal IGNYTE-ESO trial with lete-cel for people with synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) who received ≥ 2 prior lines of therapy (Press release, Adaptimmune, OCT 31, 2023, View Source [SID1234636508]).

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Additionally, Dr. Melissa Burgess of University of Pittsburgh Medical Center will present a poster summarizing results of Substudy 14 of the IGNYTE-ESO clinical trial exploring the feasibility, efficacy, and safety of lete-cel in the first-line setting for treatment-naïve patients with metastatic or unresectable synovial sarcoma or MRCLS on Thursday November 2nd at the Connective Tissue Oncology Society (CTOS) annual meeting taking place in Dublin, Ireland.

Elliot Norry, MD, Adaptimmune’s Chief Medical Officer: "The remarkable responses we are seeing in the interim analysis from IGNYTE-ESO provide us with a compelling opportunity to continue the clinical development of lete-cel for both synovial sarcoma and MRCLS. We’ll be able to leverage our learnings and capabilities from afami-cel as we consider next steps to further develop lete-cel."

Interim analysis data from the IGNYTE-ESO pivotal trial with lete-cel

Lete-cel, an engineered T-cell therapy targeted against NY-ESO-1, is being investigated for the treatment of synovial sarcoma or MRCLS in the pivotal IGNYTE-ESO (NCT03967223) trial in patients who received ≥ 2 prior lines of therapy.

The interim analysis for efficacy includes data from 45 people with synovial sarcoma or MRCLS who have received lete-cel in the IGNYTE-ESO trial and who had at least 6 months follow up. At the time of this analysis, 18/45 (40%) (99.6% CI: 20.3%, 62.3%) people with synovial sarcoma or MRCLS had RECISTv1.1 responses by independent review with two complete responses and 16 partial responses. The response rate was 9/23 (39%) for people with synovial sarcoma and 9/22 (41%) for people with MRCLS by independent review.

Duration of Response (DoR) is still being followed in 9/18 (50%) of responders at the time of the data cut-off. The median duration of response was 10.6 months (95% CI: 3.3, NE). The DoR ranges from 1.18+ to 16.6+ months and 12 out of 18 patients were censored for this analysis.

At the time of this data cut, 18/45 of people with synovial sarcoma or MRCLS had RECISTv1.1 responses with lete-cel, by independent review. The pre-defined success criteria for this planned interim analysis required at least 14 responders out of 45 patients and the primary endpoint for efficacy will require 16 responders out of 60 patients by independent review.

By investigator review, 15/45 (33%) of people with synovial sarcoma or MRCLS had RECISTv1.1 responses. The response rate was 7/23 (30%) for people with synovial sarcoma and 8/22 (36%) for people with MRCLS by investigator review.

The safety population included 73 people who had received lete-cel at the time of this interim analysis. Safety findings were consistent with the known profile of lete-cel from previous data. 65 (89%) patients had cytokine release syndrome (CRS), with the majority of CRS cases at grades 1 and 2, and 9 (12%) at grade 3 and no cases reported at Grade 4 or 5. 64 (88%) patients had hematopoietic cytopenias and the majority (86%) of events were Grade 3 or higher. Less than 5% of patients experienced immune effector cell-associated neurotoxicity (ICANS) and all events were grade 1. Overall, the safety profile of lete-cel was acceptable, including CRS and reversible hematologic toxicities.

The primary analysis will be conducted in the first half of 2024 when the 60th treated patient has 12 months of follow-up.

Data from Substudy 1 of the IGNYTE-ESO trial (CTOS 2023)

Substudy 1 was designed to explore the feasibility, efficacy, and safety of lete-cel in the first-line setting for treatment-naïve patients with metastatic or unresectable synovial sarcoma or MRCLS.

Of the five evaluable patients in the substudy, one exhibited a complete response, with an additional three partial responses, yielding an overall response rate of 80% (4/5) by investigator assessment. All five patients experienced cytokine release syndrome, all cases resolved; four were treated with tocilizumab. Overall, the substudy reveals encouraging efficacy in this small population of treatment-naïve patients in the advanced/metastatic setting with 80% ORR, with all responses ongoing at the time of this analysis.

Overview of IGNYTE-ESO trial design

IGNYTE-ESO is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of lete-cel. Lete-cel’s engineered TCR T-cells target NY-ESO-1+ tumors. NY-ESO-1 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Key eligibility criteria include ECOG performance status of 0 or 1; HLA*02 positive with confirmed NY-ESO expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 10 years; and patients must have measurable disease according to RECIST v1.1 at the time of treatment. The IGNYTE-ESO master protocol include two substudies – Substudy 1 was designed to investigate lete-cel in previously untreated advanced (metastatic or unresectable) synovial sarcoma or MRCLS; and Substudy 2 lete-cel in advanced (metastatic or unresectable) synovial sarcoma or MRCLS post-anthracycline chemotherapy. Eligible patients received lete-cel doses between 1-15 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.

Approximately 10 people were planned to be treated in Substudy 1, 5 patients were treated and enrollment was stopped. Approximately 60 people were planned to be treated in Substudy 2 and enrollment is complete.

About lete-cel 5

Lete-cel is an engineered TCR T-cell therapy against the solid tumor antigen NY-ESO-1.

About synovial sarcoma

There are approximately 50 types of soft tissue sarcomas which are categorized by tumors that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.1 Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas (there are approximately 13,400 new soft tissue cases in the U.S. each year).2 One third of patients with synovial sarcoma will be diagnosed under the age of 30.2 The five-year survival rate for people with metastatic disease is just 20% and most people undergoing standard of care treatment for advanced disease experience recurrence and go through multiple lines of therapy, often exhausting all options.

About Myxoid/round cell liposarcoma (MRCLS)

Myxoid/round cell liposarcoma (MRCLS) is a type of soft tissue sarcoma that is predominantly found in the limbs. MRCLS accounts for approximately 5% to 10% of all soft tissue sarcomas.1 One-third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations. MRCLS commonly presents at an age ranging from 35-55 years and has a poor prognosis because it recurs locally and tends to metastasize quickly and widely. The 5-year survival rate for metastatic MRCLS is only 5%.

On October 31, 2023 OncoBone Ventures enters into collaboration with India-based Mestastop Solutions, a pioneer in the metastasis field (Press release, OncoBone Ventures, OCT 31, 2023, View Source [SID1234636482]). Mestastop has dissected the whole metastasis process in three patent protected platforms METAssay, METSCAN and METVivo that they can use to identify cancer patients who are at a higher risk of metastasis, as well as pertinent targets for drug discovery.

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Arnab and Debabani Roy Chowdhury, Founders and Directors of Mestastop state: "We were happy to partner with OncoBone Ventures, who are focused on developing novel therapies for cancer patients with bone metastases, for whom there are currently no effective therapies available. The collaboration includes developing novel in vitro models as a screening platform for evaluating efficacy of therapies on cancer bone metastases."

Tiina Kähkönen, Founder and CSO of OncoBone Ventures comments: ‘We have been truly fortunate to find a collaborator like Mestastop Solutions who shares our passion to develop therapies for cancer patients with metastatic disease. Together we have the required expertise to successfully develop a pioneering in vitro bone metastasis platform that will be of great importance for the development of novel therapies affecting bone metastases."

Jussi Halleen, Founder and CEO of OncoBone Ventures adds: "OncoBone Ventures aims to utilize the developed in vitro platform as a screening tool before testing efficacy of our pipeline assets in our current in vivo Bone Metastasis Technology Platform. This will lead to faster and more cost-effective development of efficient therapies for patients with bone metastases."

More information about Mestastop Solutions in View Source

On October 31, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported its Quarterly Activities Report and Appendix 4C for the period ended 30 September 2023 (Q1 FY24) (Press release, Starpharma, OCT 31, 2023, View Source;mc_eid=bf52dd3418 [SID1234636458]). Starpharma’s closing cash balance as at 30 September 2023 was $35.6 million. Starpharma reports positive net cash inflows for the quarter of $0.4 million.

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Starpharma also recently received a $7.2 million Research and Development (R&D) Tax Incentive refund from the Australian Taxation Office after the quarter end.

"Starpharma is delighted with the recent advancements across its DEP portfolio, including completing patient recruitment for all cohorts in all three Phase 2 DEP clinical trials. The final clinical results from the Phase 2 trial of DEP cabazitaxel and interim results from the Phase 2 trial of DEP irinotecan were both highly positive and demonstrated the clinical utility, therapeutic value, and market potential of these DEP products.

"We were also pleased to showcase both DEP irinotecan and our DEP radiotheranostics pipeline at the AACR (Free AACR Whitepaper) international oncology conference this month, where the data generated a lot of interest.

"Starpharma closed Q1 FY24 in a strong cash position, with $35.6 million and a positive cash inflow this quarter. This cash balance excludes the $7.2 million R&D Tax Incentive refund we received in October 2023. With completion of our clinical programs, we also expect to see reductions in operating cash outflows in H2 FY24," said Dr Jackie Fairley, CEO, Starpharma.

Positive clinical results reported for DEP cabazitaxel and DEP irinotecan

Starpharma recently announced1 positive Phase 2 DEP cabazitaxel clinical trial results in multiple cancers, including advanced metastatic castrate-resistant prostate cancer (mCRPC), as well as other difficult-to-treat cancers, including platinum-resistant ovarian cancer and gastro-oesophageal cancers. The trial met its objectives, with endpoints demonstrating positive anti-tumour efficacy and confirming the safety and tolerability of DEP cabazitaxel.

Summary of key efficacy results for DEP cabazitaxel

Heavily pre-treated, advanced prostate cancer patients (mCRPC) treated with DEP cabazitaxel achieved a median progression-free survival (PFS) of 4.4 months, which is more than 50% longer than published data for Jevtana at the same dose2. The median overall survival (OS) of 14.7 months was also 10% longer2. The final progression-free survival result improves upon the interim data on DEP cabazitaxel reported by Starpharma at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 20223.
In advanced, platinum-resistant ovarian cancer patients who were heavily pre-treated with an average of 4 prior lines of chemotherapy, DEP cabazitaxel achieved a disease control rate (DCR) of 66.7% and an objective response rate (ORR) of 17.6%, which also compares favourably to standard-of-care therapies that report ORRs ranging from ~9 to 16%4,5,6.
In advanced gastro-oesophageal cancer patients, DEP cabazitaxel achieved a median progression-free survival (PFS) of 4.0 months and median overall survival (OS) of 8.6 months, which were 53.1% and 28.5% longer, respectively, than similar patient cohorts treated with the standard-of-care product paclitaxel7.
The positive efficacy results reported for DEP cabazitaxel in multiple cancers demonstrate the significant market potential and enhanced utility of DEP cabazitaxel, not only in the approved prostate cancer indication of Jevtana but also in other cancers that have a high unmet medical need.

During the quarter, Starpharma also announced8 positive interim clinical data for DEP irinotecan, its novel, patented nanoparticle formulation of SN38, the active metabolite of the widely used anti-cancer drug irinotecan, which is marketed by Pfizer as Camptosar. DEP irinotecan demonstrated durable anti-tumour responses in advanced colorectal cancer and platinum-resistant/refractory ovarian cancer and was very well-tolerated. Patients and clinicians have also reported significantly better tolerability than conventional irinotecan.

Summary of interim efficacy results for DEP irinotecan

DEP irinotecan monotherapy achieved durable responses for up to 72 weeks in colorectal cancer patients, with a disease control rate (DCR) of 48%; these responses are particularly positive for these patients who were heavily pre-treated, with 97% having progressed after receiving conventional irinotecan, and had exhausted their treatment options.
DEP irinotecan achieved a disease control rate (DCR) of 100% in colorectal cancer patients receiving it in combination with 5-fluorouracil (5-FU) and leucovorin (‘FOLFIRI’), with durable responses of up to 35 weeks to date. Several patients are continuing to receive DEP irinotecan treatment.
DEP irinotecan achieved a disease control rate (DCR) of 100% in ovarian cancer patients receiving DEP irinotecan monotherapy fortnightly (Q2W) and durable responses of up to 45 weeks; this cohort of heavily pre-treated patients achieved an objective response rate (ORR) of 43%, which compares favourably to the reported ORR for other treatments (~9-16%4,5,6) in patients with this stage and category of cancer.
Importantly, DEP irinotecan therapy resulted in no reports of the severe or life-threatening diarrhoea (≥ grade 3) commonly observed with conventional irinotecan. This result for DEP irinotecan across ~100 patients in the study demonstrates a significant improvement in the side effect profile compared to conventional irinotecan (Camptosar), which is associated with severe or life-threatening diarrhoea in more than 20% of patients9. This common side effect with conventional irinotecan is frequently associated with discontinuation of treatment, hospitalisation, and can be fatal. In addition, patients treated with DEP irinotecan did not experience cholinergic syndrome, an unpleasant group of adverse events reported in ~47% of patients treated with conventional irinotecan9.

Patients treated with DEP irinotecan and their oncologists have reported significantly improved tolerability and quality of life with DEP irinotecan compared to their experience with conventional irinotecan, including Camptosar.

Overall, these interim results for DEP irinotecan support the highly promising clinical utility of DEP irinotecan and its potential for application in both colorectal and platinum-resistant/refractory ovarian cancers. Starpharma completed enrolment across the trial during the quarter, with several patients continuing to receive treatment. The final Phase 2 results will be announced following completion of patient treatment and subsequent data analyses.

DEP irinotecan and DEP radiotheranostics presentations at international oncology conferences

Starpharma presented three scientific posters at the AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, US, co-hosted by the American Association of Cancer Research (AACR) (Free AACR Whitepaper), National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC) in October 2023. These posters are available on Starpharma’s website.

The posters on DEP irinotecan showcased the recent clinical results10 in advanced colorectal cancer and platinum-resistant/refractory ovarian cancer described above, and DEP irinotecan preclinical combination data11 showing the ability of Starpharma’s DEP irinotecan product to enhance the anti-tumour activity of an immuno-oncology agent, and a PARP inhibitor – both important classes of cancer treatments.

A third poster highlighted the results from a study of DEP HER2-zirconium12, Starpharma’s radiodiagnostic candidate, demonstrating promise in a HER2+ breast cancer model.

Starpharma has been invited to present at the Targeted Radiopharmaceuticals Summit Europe13, a specialist radiotheranostics conference being held in Berlin in December 2023. At the conference, Dr Jeremy Paull, Starpharma’s VP of Development and Regulatory Affairs, will present Starpharma’s DEP radiotheranostics pipeline and the benefits of the DEP platform in radiotheranostics.

Other progress across Starpharma’s DEP pipeline and partnered programs

During the quarter, Starpharma completed recruitment in the DEP docetaxel and gemcitabine combination arm. of its Phase 2 DEP docetaxel trial. As recruitment across all trial cohorts has now completed, Starpharma expects to report the final combined Phase 2 results in Q2 FY24.

Starpharma continues discussions with a number of potential commercial partners for its clinical-stage DEP assets and other partnered and preclinical DEP programs. The recently announced clinical results from these trials will support these ongoing commercial discussions.

During Q1 FY24, Starpharma also progressed its other preclinical programs in DEP antibody-drug conjugates (ADCs) and DEP radiotheranostics.

In parallel with its in-house DEP programs, Starpharma continues to make important progress across its multiple DEP partnerships with top 10 pharmaceutical companies, including MSD and Genentech, as well as Chase Sun. As previously reported, this includes an extension to Starpharma’s partnered ADC programs with MSD.

Marketed product portfolio

In August 2023, Starpharma successfully negotiated a commercial settlement agreement with Mundipharma in relation to VivaGel BV and received a $6.6 million cash payment14. Starpharma is now engaged in discussions with new potential commercial partners to expand VivaGel BV sales in these territories. VivaGel BV is a novel, non-antibiotic therapy for bacterial vaginosis, the most common vaginal infection among women of reproductive age15. VivaGel BV is registered in more than 50 countries and continues to be marketed by Starpharma’s commercial partner, Aspen, in Australia and New Zealand.

Starpharma also completed recruitment16 for its post-market clinical study of VIRALEZE in the UK, with ~200 participants with COVID-19 enrolled. The results from this study will support ongoing commercial and marketing activities for VIRALEZE, building on Starpharma’s extensive dataset and in-market experience with the product. These study results are expected to be reported in Q2 FY24, following completion of data and statistical analyses.

Starpharma and its commercial partners continue to market its broad-spectrum antiviral barrier nasal spray, VIRALEZE, through a number of e-commerce channels, including Amazon and a dedicated product website, as well as through other commercial partner arrangements. VIRALEZE is registered in over 35 countries, and the Company continues to pursue additional registration and marketing opportunities for the product. VIRALEZE is not approved for use or supply in Australia, where the review by the Therapeutic Goods Administration (TGA) for the SPL7013 nasal spray as a medical device is ongoing.

In the United States, a formal dispute resolution process is ongoing with the FDA for VivaGel BV. Starpharma is preparing to lodge a further submission to the FDA in CY23, which will include precedents of other recent FDA approvals.

Corporate

In October 2023, Starpharma’s CEO, Dr Jackie Fairley, presented at the Wilsons Drug and Device Conference17. As part of this presentation, Dr Fairley also participated in a radiotherapy panel discussion, ‘Expanding the scope for theranostics and radioligand therapies,’ alongside Clarity Pharmaceuticals and Telix Pharmaceuticals. Starpharma will also participate in the upcoming Bell Potter Healthcare Conference in November 2023.

Starpharma’s Annual General Meeting (AGM) 2023 will take place on Wednesday, 29 November 2023. Details of the AGM are available on Starpharma’s website18.

As previously advised, following Dr. Fairley’s retirement announcement, the Board commenced a search process to appoint a new CEO. The search, led by recruitment firm Heidrick & Struggles, is progressing well, with a number of impressive candidates being considered. The Board is confident of appointing a high-calibre CEO to lead Starpharma into the future.

Cash Flows for Q1 FY24

Starpharma’s cash balance as at 30 September 2023 was $35.6 million, with positive net cash inflows of $0.4 million for the quarter. Receipts from customers for the quarter were $6.8 million, which included the VivaGel BV settlement payment from Mundipharma. A $7.2 million Research and Development (R&D) Tax Incentive refund was recently received from the Australian Taxation Office after the quarter end.

Cash outflows for the quarter include research and development costs of $3.4 million related to the completion of multiple DEP clinical programs and final stages of the post-market clinical study of VIRALEZE nasal spray. R&D expenditure also included development costs for Starpharma’s targeted DEP radiotheranostics and DEP antibody-drug conjugates programs. As projected in Starpharma’s Annual Report 2023, Starpharma’s low-interest R&D Loan facility of $4.0 million with Invest Victoria was repaid in October 2023. Administration and corporate costs of $0.6 million include insurance costs, annual ASX listing fees and audit fees. Product manufacturing and operating costs for the quarter were $0.5 million. Staffing costs were $2.0 million and included non-executive and executive directors’ fees of $265,000. Other related party payments include $9,028 for consulting services to Centre for Biopharmaceutical Excellence Pty Ltd, of which Starpharma non-executive director Dr Jeff Davies is also a director and shareholder.

On October 31, 2023 – 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 the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 30 September 2023 (Q1 FY24) (Press release, Immutep, OCT 31, 2023, View Source [SID1234636456]).

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EFTI DEVELOPMENT PROGRAM FOR CANCER

In August 2023, Immutep received positive scientific advice from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for the continued development of efti. The CHMP advised further toxicology studies are not needed for a future Marketing Authorisation Application (MAA) for efti in Europe. Similar advice was received from the US Food and Drug Administration (FDA) for a potential future Biologics License Application (BLA).

The Company also received regulatory authorisation in September 2023 for efti manufactured at commercial 2,000L scale for use in clinical trials across multiple European countries including Germany, Belgium, Denmark and the United Kingdom. This followed the successful scale up of the manufacturing process of efti (from the 200L process) to commercial scale at WuXi Biologics. Immutep will introduce efti manufactured by the 2,000L scale process into current and future clinical trials.

TACTI-002 (KEYNOTE-PN798)
Phase II clinical trial evaluating efti + KEYTRUDA (pembrolizumab) 1st line Non-Small Cell Lung Cancer (1L NSCLC) Following the end of the quarter, Immutep reported excellent Overall Survival results from efti in combination with KEYTRUDA in patients with metastatic NSCLC at the ESMO (Free ESMO Whitepaper) Congress 2023 in Spain in October. Exceeding expectations, median Overall Survival has reached 35.5 months in NSCLC patients expressing PD-L1 (patients with a Tumour Proportion Score (TPS) of ≥1%), 23.4 months in patients with low PD-L1 expression (TPS 1-49%) and encouragingly, has not yet been reached in patients with high PD-L1 expression (TPS ≥50%).

A 35.5-month survival benefit gives these patients 12 to 18 months of additional survival compared to historical data from the current best approved option: pembrolizumab in combination with doublet chemotherapy (see Table 1). In addition to the substantial survival benefit, the combination of efti and pembrolizumab is chemo-free, avoiding the toxic side effects seen in chemo options. Efti is enabling deep, durable responses for patients regardless of PD-L1 expression with a favourable safety profile in line with antiPD-1 monotherapy.

Therapy Median Overall Survival
Efti + Pembrolizumab 35.5 months
Pembro + Doublet Chemo (NSQ)* 23.3 months
Pembro + Doublet Chemo (SQ)* 18.9 months
Ipilimumab + Nivolumab 17.1 months
Pembrolizumab monotherapy 16.4 months
Ipi + Nivo + 2 cycles Doublet Chemo 15.8 months
* NSQ = Non-squamous; SQ = Squamous

TACTI-003 – Phase IIb clinical trial in 1st line HNSCC

The Phase IIb TACTI-003 trial is ongoing in patients with 1st line HNSCC. Patient recruitment reached ~99% in October and is expected to be complete in November 2023. The primary analysis according to the trial protocol will be performed after all subjects in the randomized part have completed at least three cycles of treatment (18 weeks in total) or discontinued the trial. The Company expects to report data from the trial in H1 CY2024. TACTI-004 – Phase III registrational trial in 1st line NSCLC Throughout the quarter, Immutep continued its preparations to commence the

TACTI-004 trial.

The trial is expected to start in CY2024.

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

Patient recruitment into the AIPAC-003 trial continued throughout the quarter with 15 clinical sites now actively recruiting. Six patients were enrolled and have completed the dose limiting toxicity (DLT) window of the first cycle in the open-label safety lead-in portion. The safety evaluation of the six patients is underway with the Independent Data Safety Monitoring Committee (IDMC) review meeting planned for beginning of November 2023. If no dose limiting toxicities are observed in those six patients, the randomized dose optimization (Phase II) part can start in Q4 CY2023.

INSIGHT-003 – Phase I in 1st line NSCLC

At the ESMO (Free ESMO Whitepaper) Congress 2023 in October, further encouraging efficacy and tolerability data was presented from the ongoing investigator-initiated INSIGHT-003 trial evaluating efti plus anti-PD-1 therapy and doublet chemotherapy as 1st line therapy in metastatic non-squamous non-small cell lung cancer.

A strong Overall Response Rate of 71.4% and 90.5% Disease Control Rate were reported. Median Overall Survival (OS) has not yet been reached. The median Progression Free Survival (PFS) was 10.1 months.

In this study, 81% of patients have low or negative PD-L1 expression, making them typically less responsive to anti-PD-1 based therapy. For low or negative PD-L1 expressors (TPS <50%), the ORR was 70.6% which compares favourably to reported results from a registrational trial of anti-PD-1 and doublet chemotherapy that yielded a response rate of 40.8% in the same patient population.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma

Following receipt of regulatory approvals to initiate INSIGHT-005, preparationsto commence this investigatorinitiated trial are continuing at the Frankfurt Institute of Clinical Cancer Research, IKF.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma

The first soft tissue sarcoma (STS) patient was enrolled and safely dosed in the Phase II EFTISARC-NEO trial in July. The trial is the first chemo-free triple combination therapy of efti and is the first to evaluate it in a neoadjuvant setting. STS is an orphan disease with high unmet medical need and poor patient prognosis. Currently six patients have been recruited into this trial which is funded by a Polish grant program.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

During the quarter, Immutep commenced the toxicology study evaluating the safety and toxicity of IMP761, the Company’s proprietary preclinical candidate. IMP761 is the world’s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. The study is a key step before first-in-human trials can begin.

INTELLECTUAL PROPERTY

Immutep was granted two new patents during the quarter. A new patent protecting IMP761 was granted in September by IP Australia, the Australian Government’s patent agency. The Company was also granted a new patent by the Brazilian Industrial Property Office in September protecting Immutep’s potency assay for release testing of efti. This assay is used in the commercial-scale (2,000L) manufacturing process for efti. The Brazilian patent follows similar patents granted in Japan and Australia in 2023, and Korea in 2022.

FINANCIAL SUMMARY

Immutep continued to prudently manage its cashflow over the first quarter of the new financial year (Q1 FY24), while strategically investing into clinical trial programs for efti.

With a cash and cash equivalent balance as at 30 September 2023 of approximately $110.1 million, Immutep’s cash position remains very strong with an expected cash reach till early CY2026.

The Company has sufficient capital to reach key milestones that will potentially add value to efti and IMP761.

Cash receipts from customers in Q1 FY24 were $132k, compared to $16k in Q4 FY23. The net cash used in G&A activities in the quarter was $1.61 million, which is the same as Q4 FY23.

Payments of $464k to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, comprises Non-Executive Directors’ fees and Executive Directors’ remuneration.

The net cash used in R&D activities in the quarter was $9.72 million, compared to $5.41 million in Q4 FY23. The increase in cash used for the quarter was mainly due to increased clinical trial activities.

Total net cash outflows used in operating activitiesin the quarter was $12.86 million compared to $8.35 million in Q4 FY23.

Payment for the acquisition of Intellectual Property was $328k in Q1 FY24, compared to nil in Q4 FY23.

A copy of the Appendix 4C-Quarterly Cash Flow Report for the quarter is attached.

On October 30, 2023 Shenzhen Kaiyue Life Science Co., Ltd. (hereinafter referred to as "Kaiyue Life"), a world-first RNA helicase drug target, has developed the first-in-class (FIC) drug with independent intellectual property rights worldwide for a wide spectrum of solid tumors, reported the first milestone event in drug development: obtaining clinical trial approval from the US FDA, achieving a leap from zero to one (Press release, KeYe Life Technologies, OCT 30, 2023, View Source;article_id=78 [SID1234644609]).

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Based on more than ten years of basic research, Kaiyue Life has developed a unique target for special RNA helicase proteins as cancer treatment, which is internationally leading and original, and is classified as a Class 1.1 original new drug. This is an original drug target developed by us. It took ten years from the start of basic research to target confirmation, and two and a half years from PCC to IND approval.

Kaiyue Life has been deeply involved in the field of RNA helicase and is a pioneer in the field of RNA helicase research and development. The founder of the team has been engaged in helicase research since 2008 and has published dozens of high-level scientific research papers to date.

RNA helicase plays an important role in the gene expression process of eukaryotes. Its functions involve embryonic development, cell proliferation, hematopoiesis, metabolism, cancer, immune regulation, inflammatory response and autoimmune diseases. Their disorders can cause a variety of human diseases, such as cancer, viral infection, inflammation, etc. Some DEAD/H box proteins are considered to be therapeutic targets for diseases. For example, inhibitors of eIF4A and DDX3X are currently being developed as new targeted drugs for the treatment of human cancer. In view of the close correlation between RNA helicase and human diseases, several helicase inhibitors have entered clinical research as drugs for indications such as tumors and antivirals.

Dr. Zhang Yandong, founder of Kaiyue Life, said: Drug research and development in the field of RNA helicase is in the ascendant.