Alchemia Announces Database Lock of Its HA-Irinotecan Pivotal Phase III Trial in Metastatic Colorectal Cancer

BRISBANE, AUSTRALIA--(Marketwired - Oct 9, 2014) - Alchemia Limited (ASX: ACL)

• Database lock triggers commencement of primary endpoint analysis
• 350 progression free survival events achieved
• Top-line results expected by the end of October

Alchemia Limited (ASX: ACL), a drug discovery and development company, announced today the database lock for the primary efficacy analysis of its pivotal Phase III trial of HA-Irinotecan in metastatic colorectal cancer (mCRC). The company also confirms that the trial achieved its primary endpoint analysis threshold of a minimum of 350 progression free survival (PFS) events. The statistical analysis of the clinical study was designed to commence when 350 progression-free survival events had been confirmed by the trial's independent Imaging Review Committee.

The database lock means no further changes to the trial data will occur and that data analysis will commence. The data collection and reconciliation, as well as the query resolution procedures and quality control have been completed, enabling the locking of the database. The validated dataset has been finalised and submitted to Alchemia's project statisticians for analysis pursuant to the trial's protocols. Results for the trial, which has successfully completed four safety reviews by the Data Safety Monitoring Board (DSMB), are expected to be released by the end of October 2014.

"We are excited to reach the final stage of the Phase III trial process, and we look forward to the results of this trial, which has the potential to substantially impact the current second and third-line treatment regimen for patients with metastatic colorectal cancer," said Alchemia CEO Thomas Liquard. "A successful trial would be transformational for Alchemia as our further validated HyACT platform could then be applied to many different chemotherapy agents used against a broad range of solid tumours. We will complete the data analysis and will issue the results of the Phase III study in the coming weeks."

The Phase III trial enrolled 415 patients across 76 clinical centres worldwide. It was a randomized, double-blinded, active controlled study of Alchemia's proprietary HyACT technology formulated with the well-known chemotherapeutic drug, irinotecan. HA-Irinotecan or irinotecan were administered as part of the conventional FOLFIRI chemotherapy regimen (combination of folinic acid, fluorouracil and irinotecan) in patients with mCRC who were candidates for second or third line chemotherapy. The primary objective of this trial was to demonstrate superiority in progression free survival (PFS) of Alchemia's HA-Irinotecan over irinotecan.

"The collection and processing of the Phase III clinical trial data marks an important point in the development of the HyACT technology and we are hopeful that the results will provide strong clinical rationale for targeting CD44 on solid tumours via Hyaluronic Acid," said Dr. Tracey Brown, Alchemia's Chief Scientific Officer and HyACT inventor. "There is a real need for more efficacious treatments in mCRC, and we are now one step closer to potentially offering patients a new treatment to fight their disease."

Colorectal cancer is one of the most common cancers in the world, with over 1.2 million new cases diagnosed annually¹ and is the second leading cause of cancer deaths in the US, claiming more than 50,000 lives each year². More than $7.5B is spent annually on colorectal cancer drug treatments across the major markets (US, EU and Japan)³. More than 100,000 second and third line mCRC patients are treated annually with chemotherapy in the US, EU and Japan, representing an addressable market for HA-Irinotecan well above $1B⁴.

"If the FOLFIRI regimen containing HA-Irinotecan succeeds in demonstrating superiority when compared to FOLFIRI, it has the potential to become the standard of care for mCRC and could significantly alter the treatment landscape," said Dr. Peter Gibbs, the principal trial investigator.

¹ WHO, IARC GLOBOCAN, Cancer Incidence and Mortality Worldwide in 2008 at http://globocan.iarc.fr/. Accessed February 21, 2014
² http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3. Accessed February 21, 2014.
³ Decision Resources, 2012
⁴ Intrinsiq 2014 (US), Decision Resources 2013 (EU/Japan)

About the HyACT Platform and HA-Irinotecan

HyACT is a technology platform used to transport cancer drugs to tumours and is designed to increase the effectiveness of the drug against tumours without increasing treatment toxicity. HyACT uses a material called hyaluronic acid, or HA, to deliver increased amounts of cancer drugs preferentially to tumour cells. HyACT binds to the activated receptor CD44, which is known to be present in high levels in the majority of cancer types but, importantly, is generally not activated in healthy tissue. As a result, HyACT drugs are able to efficiently deliver high concentrations of cancer drugs into CD44-expressing tumour cells without increasing treatment toxicity in healthy tissue. CD44 over-expression is associated with more aggressive, metastatic tumours and is also a marker for cancer stem cells, which are believed to be responsible for treatment failure of current chemotherapeutic drugs.

HA-Irinotecan is the most advanced product using the HyACT technology. In addition to the pivotal trial in mCRC (https://clinicaltrials.gov/ct2/show/study/NCT01290783), HA-Irinotecan is also currently being evaluated in two investigator-led Phase II trials. The CHIME study, a collaboration with Merck Serono, is investigating the clinical safety and efficacy for HA-Irinotecan as a component of the FOLFIRI regimen when used in conjunction with the biological therapy Erbitux (cetuximab) in patients with mCRC. HA-Irinotecan is also being studied in an investigator-led Phase II clinical trial focusing on small cell lung cancer (SCLC). The objectives of this trial are to determine whether HA-Irinotecan is capable of targeting and eradicating CD44-expressing small cell lung cancer stem cells and to demonstrate that HA-Irinotecan/carboplatin provides a clinically significant benefit (safety and/or efficacy) over irinotecan/carboplatin, in patients with advanced SCLC.

About Alchemia Limited

Alchemia is a drug discovery and development company marketing fondaparinux, an FDA approved injectable antithrombotic, in the US as well as in other markets via partner Dr. Reddy's Laboratories. The Company is progressing an oncology pipeline with several ongoing preclinical and development programs through its proprietary HyACT drug delivery platform, which targets anti-cancer drugs to solid tumours. Lead asset HA-Irinotecan is in a pivotal Phase III clinical trial for the treatment of metastatic colorectal cancer. HA-Irinotecan is also in two Phase II investigator-sponsored trials, one of which is in collaboration with Merck Serono combining HA-Irinotecan with Erbitux^® (cetuximab). In March 2014, Alchemia also announced the in-licensing of two new pre-clinical oncology compounds targeting the FAK pathway.

Alchemia is also evaluating additional small molecule drug discovery targets via the VAST internal discovery platform, which is based on the Company's deep chemistry expertise. The VAST technology is being developed in collaboration with leading academic institutions and is partnered with AstraZeneca AB.

Erbitux^® is a trademark of Merck KGaA.