Melbourne, Australia; 20 April 2023: Starpharma (ASX: SPL, OTCQX: SPHRY) today announces AZD0466 results from a preclinical study in small cell lung cancer (SCLC) patient-derived xenograft (PDX) models. Starpharma’s partner, AstraZeneca, presented these results overnight at the American Association for Cancer Research (AACR) Annual Meeting.

AZD0466 is a highly optimised dendrimer nanoparticle formulation of AstraZeneca’s dual Bcl‑2/xL inhibitor, AZD4320, which utilises Starpharma’s DEP^® technology and is being developed by AstraZeneca under their multi-product DEP^® license with Starpharma. AZD0466 is the first candidate under Starpharma’s multi-product license with AstraZeneca whereby Starpharma is eligible to receive development, launch and sales milestones, in addition to royalties.

The AACR Annual Meeting is one of the world’s largest cancer research conferences, bringing together thousands of investigators, scientists, and clinical researchers to discuss new and significant observations.

SCLC is an aggressive form of lung cancer with relatively few treatment options and a 5-year survival rate of only ~7%[1]. The results from this latest research in SCLC presented by AstraZeneca at the AACR Annual Meeting showed that Bcl-2/xL inhibition has therapeutic potential in SCLC:

• AZD0466 was active in 50% of SCLC models, resulting in tumour regression in 33% of models.
• Dual Bcl-2/xL inhibitor AZD0466 outperformed marketed Bcl-2 inhibitor venetoclax[2] in 60% of SCLC models.
• Notably, AZD0466 was also active in models resistant to the current standard-of-care treatment for SCLC: platinum/etoposide chemotherapy.

In addition to the preclinical data in SCLC, the poster presented by AstraZeneca at the AACR Annual Meeting also included newly released clinical trial data from AstraZeneca’s first-in-human study of AZD0466 in patients with advanced solid tumours (NCT04214093). In this clinical trial (NCT04214093), 9 patients with adrenal carcinoma, anal cancer, bile duct cancer, bladder/urethral cancer, colorectal cancer, lung cancer, pancreatic cancer, and sarcoma were treated with AZD0466. Of the 9 patients treated with AZD0466 in this trial, efficacy signals were observed in 33% of these patients who achieved stable disease for periods of up to 5.5 months.

AZD0466 is also currently being evaluated in patients with advanced haematological malignancies (NCT04865419) and non-Hodgkin lymphoma (NCT05205161). 33[3] patients have been treated with AZD0466 across the advanced solid tumour and advanced haematological malignancy trials.

The AstraZeneca poster included updated clinical data from the ongoing global Phase 1/2 clinical trial in patients with advanced haematological malignancies (NCT04865419). This trial has now treated 24[4] patients at doses up to 3600mg, with patient treatment ongoing and further dose escalations planned. This trial continues to progress well, with no dose-limiting toxicities reported to date and with initial clinical activity observed through reduction of bone marrow blasts following AZD0466 treatment and a mean treatment duration of 4.4 months. This Phase 1/2 trial in patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) continues to enroll at 18 sites across the United States, Europe, Asia and Australia, with additional sites planned.

These new preclinical and clinical results for AZD0466 were presented in a poster presentation by AstraZeneca at the AACR Annual Meeting overnight. The poster and corresponding abstract are appended and will be available on Starpharma’s website: www.starpharma.com. In addition to the poster presentation, AZD0466 featured at AstraZeneca’s booth at the AACR Annual Meeting, as part of their haematology development portfolio, through an interactive display highlighting AstraZeneca’s clinical pipeline and portfolio.

Starpharma’s dendrimer drug delivery technology, known as DEP^®, is used to enhance the therapeutic properties of drugs to improve solubility, efficacy, pharmacokinetics, targeting, and to reduce certain toxicities. Starpharma has established partnerships with three of the world’s largest pharmaceutical companies – AstraZeneca, MSD, and Genentech – and has also developed three clinical-stage anticancer products based on its DEP^® technology, with others in preclinical development.

Dr Jackie Fairley, Starpharma CEO, commented: “It is exciting to see AstraZeneca continue to invest in the preclinical and clinical development of their licensed DEP^® product, AZD0466. This AZD0466 poster presentation in Small Cell Lung Cancer at one of the world’s largest cancer research conferences – the American Association for Cancer Research – adds to the growing body of preclinical and clinical data AstraZeneca is generating for this innovative anti-cancer product, which was developed using Starpharma’s DEP^® technology.

“AZD0466 is already being trialed globally in patients with advanced leukaemias and non-Hodgkin lymphoma. The preclinical and clinical results presented at AACR are encouraging and the positive data in SCLC may lead to an expanded market opportunity for AZD0466 and, importantly, bring a potentially more efficacious product to patients in need. We look forward to seeing further data and clinical progress for AZD0466.”

About AZD0466 and Starpharma’s multi-product DEP^® license with AstraZeneca

AZD0466 is a highly optimised dendrimer nanoparticle formulation of AstraZeneca’s dual Bcl-2/xL inhibitor, AZD4320, which utilises Starpharma’s DEP^® technology and is being developed by AstraZeneca under their multi-product DEP^® license with Starpharma. AZD0466 is in a novel class of oncology drugs called dual Bcl-2/xL inhibitors which seek to overcome drug resistance which occurs in treatment with BcL-2-specific inhibitors including venetoclax. AZD0466 allows for efficient delivery of AstraZeneca’s dual Bcl-2/xL inhibitor, with an optimised release profile also designed to reduce the potential for toxicities associated with dual Bcl-2/xL inhibition. Dual Bcl-2/xL inhibition with AZD0466 also has the potential for broader activity than the marketed Bcl-2-specific inhibitor, venetoclax (Venclexta^®).

AZD0466 is the first candidate under Starpharma’s multi-product license with AstraZeneca. Starpharma is eligible to receive development, launch and sales milestones, in addition to royalties. To date, Starpharma has received US$7M in milestones for AZD0466, with the potential to receive milestones of up to US$124M, plus royalties.

View the full Announcement here. 

View the Poster here.

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

[2] Venetoclax is an oral medication, sold under the brand names Venclexta and Venclyxto, used to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or acute myeloid leukemia.

[3] Anderson C L et al. AZD0466, a dual BCL-2/XL targeting nanomedicine, is active in small cell lung cancer models [abstract]. In: Proceedings of the 114th Annual Meeting of the American Association for Cancer Research; 2023 April 14-19; Orlando, FL. Philadelphia (PA): AACR; 2023. Abstract nr 6150/12

[4] Patient data as at 24 January 2023