Highlights:

• Completed enrolment and treatment of patients for the Phase 2 clinical trial of DEP^® cabazitaxel
• Completed enrolment and treatment of patients for the Phase 2 monotherapy trial of DEP^® docetaxel
• AstraZeneca AZD0466 DEP^® program reported encouraging results and progress at international oncology conference:
  • AZD0466 well tolerated in patients with advanced solid tumours, with efficacy signals (stable disease) in 33% of patients for up to 5.5 months
  • Dose escalation continues in the global Phase 1/2 trial of AZD0466 in advanced haematological malignancies; initial efficacy signals observed from AZD0466 in patients through reduction of bone marrow blasts and no dose-limiting toxicities reported to date
  • AZD0466 also shown to be active in preclinical small cell lung cancer (SCLC) models, including models resistant to the current standard-of-care treatments for SCLC
• Starpharma’s HER2-targeted DEP^® SN-38 antibody-drug conjugate (ADC) shown to outperform the approved ADC product, Enhertu^®[1], with significant anti-tumour activity and improved survival in a HER2+ human ovarian cancer xenograft model
• Post-market clinical study of VIRALEZE™ nasal spray in people with COVID-19 is well advanced, with more than 70% of participants recruited to date
• Strong cash position of $38.9 million at 31 March 2023

Melbourne, Australia; 28 April 2023: Starpharma (ASX: SPL, OTCQX: SPHRY) today releases its Quarterly Activities Report and Appendix 4C for the period ended 31 March 2023 (Q3 FY23). Starpharma’s net operating cash outflows for the quarter were $4.9 million, and the closing cash balance as at 31 March 2023 was $38.9 million.

Internal Clinical DEP^® Programs

Starpharma has now completed enrolment and treatment of patients for both of its Phase 2 monotherapy clinical trials of DEP^® cabazitaxel and DEP^® docetaxel.

The Phase 2 clinical trial of DEP^® cabazitaxel enrolled a total of 76 patients across sites in the United Kingdom (UK) and Australia, with the final patient having recently completed treatment. Encouraging efficacy signals, including significant tumour shrinkage and substantial tumour biomarker reductions, have been observed in multiple cancer types, including prostate, ovarian, gastro-oesophageal, cholangiocarcinoma, and head and neck cancer, following treatment with DEP^® cabazitaxel. Starpharma and its specialist clinical research organisation are now focused on follow-up and finalising the patient data set and quality control processes. At this stage, Starpharma expects to report top-line results from the Phase 2 clinical trial of DEP^® cabazitaxel during Q3 CY23, following the final requisite data verification and review.

The Phase 2 trial of DEP^® docetaxel has also now completed both enrolment and treatment of patients in the monotherapy arm. A total of 80 patients have been enrolled across the monotherapy and combination arms of the DEP^® docetaxel clinical trial to date.

The DEP^® docetaxel clinical program includes two combination arms: the already completed DEP^® docetaxel plus nintedanib arm in lung cancer and the ongoing DEP^® docetaxel plus gemcitabine arm, which is focused on pancreatic cancer. In the Phase 2 monotherapy arm of the DEP^® docetaxel trial, a total of 50 patients have been enrolled across multiple sites in the UK. Encouraging efficacy signals, including prolonged stable disease and significant tumour shrinkage, have been observed in heavily pre-treated patients (typically having failed multiple other treatments, including taxanes) with cancers including pancreatic, gastro-oesophageal and cholangiocarcinoma. Patients treated with DEP^® docetaxel did not experience any hypersensitivity reactions, including anaphylaxis, and had a notable lack of bone marrow toxicity (e.g., neutropenia) and other common side effects such as hair-loss, mouth ulcers and oedema, as compared to conventional docetaxel. Both neutropenia and severe hypersensitivity/anaphylaxis are considered serious toxicities associated with conventional docetaxel treatment, and can be dose limiting and potentially fatal. Recruitment for the DEP^® docetaxel and gemcitabine combination arm is ongoing, and Starpharma expects to report the results of the DEP^® docetaxel monotherapy and available combination data during Q3 CY23.

Starpharma’s Phase 2 clinical trial of DEP^® irinotecan continued to progress during the quarter, with 94 patients now recruited across both the monotherapy and the 5-FU/leucovorin (equivalent to the commonly used ‘FOLFIRI’ regimen) combination arms. Starpharma is continuing to enrol patients in this trial, with recruitment for the monotherapy cohort in the final stages. Encouraging efficacy signals with DEP^® irinotecan have been observed in multiple tumour types, including colorectal, breast, pancreatic, lung, and oesophageal, including in heavily pre-treated patients, some of whom have failed to respond to previous treatment with conventional irinotecan.

In parallel with completing enrolment and treatment of patients in these clinical trials, licensing activities are ongoing for all three products as part of Starpharma’s DEP^® commercialisation strategy.

Partnered DEP^® Programs

AstraZeneca recently presented new clinical and preclinical data on AZD0466 at the 2023 AACR Annual Meeting held in Orlando, Florida. Newly released clinical data from AstraZeneca’s first-in-human trial (NCT04214093), which treated 9 patients with advanced solid tumours, showed that AZD0466 was well tolerated, with efficacy signals (stable disease) observed in 33% of patients for up to 5.5 months. AstraZeneca’s AZD0466 poster at the AACR Annual Meeting also included updated clinical data from the ongoing global Phase 1/2 clinical trial of AZD0466 in patients with advanced haematological malignancies (NCT04865419). This trial has now treated 24 patients at doses up to 3600mg, with patient treatment ongoing and further dose escalations planned. Initial clinical activity has been observed through reduction of bone marrow blasts following AZD0466 treatment, with the mean treatment duration being 4.4 months to date.

In addition to these new clinical data, AstraZeneca also presented results from a preclinical study of AZD0466 in patient-derived small cell lung cancer (SCLC) models at the AACR Annual Meeting. SCLC is an aggressive form of lung cancer with limited treatment options and a five-year survival rate of ~7%[2]. The positive results presented showed that AZD0466 was active in 50% of SCLC models, with regression in 33% of models. Notably, AZD0466 was active in models resistant to the standard-of-care treatment for SCLC patients (platinum/etoposide), and also outperformed the marketed BcL-2 inhibitor, venetoclax, in 60% of models.

Both clinical trials of AZD0466 in patients with advanced haematological malignancies (NCT04865419) or non-Hodgkin lymphoma (NCT05205161) continue to progress, with recruitment ongoing at sites in the USA, Europe, Asia, and Australia.

In parallel with the recent and upcoming developments of AZD0466, Starpharma’s DEP^® partnerships with MSD, Genentech and Chase Sun continue to progress well, with significant activity across our partnered programs during the quarter.

Internal Preclinical DEP^® Programs

Alongside advancing Starpharma’s internal clinical DEP^® programs, the Company continued to progress its preclinical programs in the areas of DEP^® antibody drug conjugates (ADCs) and DEP^® radiotheranostics, which are also the subject of other commercial and collaborative discussions.

This week, Starpharma announced[3] results for a new DEP^® ADC, HER2-targeted DEP^® SN-38 ADC, which demonstrated significant anti-tumour activity (p<0.0001) and improved survival in a HER2+ human ovarian cancer model (SKOV-3), outperforming the marketed HER2 ADC, Enhertu^®. ADCs represent an innovative area of cancer treatment, with the global ADC market expected to reach USD ~$22.9 billion in 2030[4]. Starpharma’s DEP^® platform delivers a number of advantages in ADCs, including its ability to achieve higher drug-to-antibody ratio (DAR), and therefore higher drug payload, than conventional ADCs; its greater flexibility in terms of linker strategies to precisely control drug release profiles; and its ability to widen the therapeutic index of toxic drug payloads.

Marketed Products

Marketing and commercialisation of Starpharma’s nasal spray, VIRALEZE™, continues in Europe, UK, Italy, Vietnam, Hong Kong and Macau. In Hong Kong, Starpharma’s distribution partner, Hengan, recently partnered VIRALEZE™ with the Hong Kong Premier League football club, Kitchee SC. In addition to distribution through LloydsPharmacy UK, Starpharma has recently expanded the VIRALEZE™ e-commerce channels in the UK. Product is expected to also be available through a dedicated VIRALEZE™ product UK webstore ithin the next week and through other online channels within the next month. VIRALEZE™ is not approved for use or supply in Australia, and these additional online channels in the UK are not accessible in Australia. In parallel, Starpharma continues to pursue registration and commercialisation of VIRALEZE™ in other countries, with the Company continuing to focus on commercially attractive markets with rapid regulatory pathways.

Starpharma’s post-market clinical study of VIRALEZE™ nasal spray in people with COVID-19 is recruiting well, with  more than 70% of participants enrolled to date. The study continues to enrol participants at Ashford and St Peter’s Hospitals NHS Foundation Trust (ASPH) in the southwest London region and surrounding areas. As previously announced, the results from this post-market clinical study in COVID-19-positive participants will support ongoing marketing, regulatory and commercial activities for VIRALEZE™.

In Australia, the review by the Therapeutic Goods Administration (TGA) for the SPL7013 nasal spray as a medical device is ongoing.

During the quarter, Starpharma supplied product to both of its VivaGel^® BV partners, Mundipharma and Aspen, to support sales and marketing activities in their licensed regions. Further VivaGel^® BV registrations and product launches are planned in the Middle East and Southeast Asia. Product has been supplied to these regions and launch activities are well advanced. Marketing campaigns by partners to build brand awareness and sales are ongoing, including for consumer and healthcare professional audiences.

In the United States, a formal dispute resolution process is ongoing with the FDA for VivaGel^® BV. As part of this process, Starpharma has had extensive external advice, met with the FDA multiple times, and made a number of submissions of data and analyses to the FDA. The Company is preparing to lodge a further submission to the FDA this year. This submission will include precedents of other FDA approvals with the timing of lodgement now governed by the publication and incorporation of the relevant precedent information.

Commenting on the quarter, Starpharma CEO, Dr Jackie Fairley, said: “Starpharma’s DEP^® technology is showing continued momentum across our commercial partnerships and in-house programs. We are pleased to report completion of recruitment and treatment for both our Phase 2 monotherapy trials of DEP^® docetaxel and DEP^® cabazitaxel in parallel with partner presentations at international conferences and recent results for Starpharma’s  HER2-targeted DEP^® antibody drug conjugate.

“It was exciting to see Starpharma’s commercial partner, AstraZeneca, present new clinical data for our partnered DEP^® product, AZD0466, in advanced solid tumours where they reported good tolerability across the cohort as well as stable disease in 33% of patients. In addition, patient recruitment and dose escalation continue in the two global Phase 1/2 trials of AZD0466 in haematological malignancies, with no dose-limiting toxicities reported to date and initial clinical activity observed in patients.

“Starpharma’s post-market clinical study of VIRALEZE™ in people with COVID-19 is recruiting ahead of schedule in the UK, with more than 70% of participants enrolled to date. Marketing and commercialisation activities for VIRALEZE™ continue, including in Hong Kong, Vietnam, UK, and Europe, alongside regulatory activities in other countries.”

Cash Flows for the Quarter

Starpharma’s cash balance as at 31 March 2023 was $38.9 million, with net operating cash outflows of $4.9 million for the quarter. Receipts from customers were $0.6 million, including from VIRALEZE™ and VivaGel^® BV product sales. Cash outflows of $2.4 million for research and development includes the costs for Starpharma’s internal DEP^® clinical programs, which are at advanced stages, having recently completed recruitment for both DEP^® cabazitaxel and DEP^® docetaxel monotherapy. Product manufacturing and operating costs were $1.2 million and include inventory and manufacturing costs related to the ongoing supply of VIRALEZE™ and VivaGel^® BV. Staffing costs were $2.0 million and include non-executive and executive directors’ fees of $252,000.

View/Download the ASX Announcement here. 

[1] ENHERTU^® is a registered trademark of Daiichi Sankyo Company Limited. Enhertu^® comprises the humanised monoclonal antibody/HER2-directed antibody, trastuzumab, covalently linked to a topoisomerase I inhibitor payload, DXd (an exatecan derivative)

[2] Gazdar A et al. Nat Rev Cancer 2017

[3] ASX Announcement titled, ‘HER2-targeted DEP SN38 ADC outperforms in HER2 cancer model’, dated 26 April 2023

[4] https://www.grandviewresearch.com/industry-analysis/antibody-drug-conjugates-market