On January 28, 2022 Race Oncology reported the December 2021 quarter (Q2 FY 2022) was highlighted by new pre-clinical findings that Zantrene reduces anthracycline and carfilzomib-induced heart damage, while also improving the cancer cell killing effects of both drugs (ASX announcements: 22 November 2021 & 8 December 2021) (Press release, Race Oncology, JAN 28, 2022, View Source [SID1234610000]).
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A second highlight was the strong support of our shareholders in funding the new and expanded Three Pillar strategy shared at Race’s Annual General Meeting (ASX announcement: 23 November 2021). This support enables the Company to progress the following clinical programs: Phase 1b/2 FTO solid tumour clinical trial ($8.0 million); cardio-protection Phase 2b clinical trial in breast cancer patients ($7.5m); Phase 2 Extramedullary Acute Myeloid Leukaemia (AML) / Myelodysplastic syndrome (MDS) clinical trial in Europe ($9.2 million); enhanced formulations of Zantrene ($3.2 million); preclinical cardio-protection studies ($1.0 million) and the development of new molecules ($0.8 million). Shareholder subscriptions of $44 million were received with $29.7 million accepted (ASX announcement: 21 December 2021) in line with the full case funding proposal. More broadly the team made continued progress in its Australian EMD AML program announcing the ethics documentation submission (ASX announcement: 1 November 2021), the securing of two additional USA patents (ASX announcements: 6 October 2021 & 19 October 2021) and adding new R&D development capability via a collaboration with the University of Wollongong (ASX announcement: 9 November 2021) to further support formulation and new drug developments. In sum, the quarter saw considerable progress and the Race team is now appropriately funded to progress and accelerate the expanded clinical and preclinical program.
Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com Key events of the quarter § On 6 & 19 October 2021, Race announced that it had been granted its fifth and sixth USA patents, providing additional protection around the use, formulation, and compositions of Zantrene for improving the efficacy of related treatments. § On 27 October 2021, Race announced a FTO biomarker research collaboration with Chaim Sheba Hospital, Israel. This research program will see analysis of clinical patient samples by Dr Dom Dominissini, to assess FTO biomarker and m6A RNA methylation status in patients treated with Zantrene. § On 1 November 2021, Race announced submission of its human ethics application to commence a Phase 1b/2 extramedullary AML & MDS trial. This clinical program underpins future registration trials in the EU and US for Zantrene. The study is led by Associate Professor Anoop Enjeti (Calvary Mater Hospital Newcastle) with the support of the Contract Research Organisation, Parexel. §
On 3 November 2021, Race initiated a collaboration study to develop a genomicsbased companion diagnostic for Zantrene to support its use as a precision oncology drug. This study will be led by the experienced genomics researcher Professor Murray Cairns at the University of Newcastle. The study will utilise the latest RNA genomics tools to identify genetic biomarkers associated with a cancer’s sensitivity to Zantrene at the patient specific level. § On 9 November 2021, Race announced initiation of a strategic collaboration with The University of Wollongong, focused on the optimisation of new formulations to support long-acting peripheral intravenous delivery (IV) delivery of Zantrene.
This collaboration will also pursue the development of an oral formulation of Zantrene. The collaboration will be led by experienced oncology formulator, Professor Marie Ranson in collaboration with Race’s Principal Scientist, Professor Michael Kelso, and is supported with the appointment of Race’s Senior Scientist, Dr Ben Buckley. § On 22 November 2021, Race announced a preclinical breakthrough heart protection discovery for Zantrene. While anthracyclines are effective anti-cancer drugs they carry a serious risk of causing permanent heart damage. Zantrene was shown to protect heart muscle from anthracycline-induced cell death when used in combination. Furthermore, a Zantrene/doxorubicin combination was also found to better kill cancer cells.
This effect was independent of Zantrene FTO inhibiting activity, and provides Race with an entirely novel commercial opportunity. § On 23 November 2021, Race announced an update to its "Three Pillar" Strategy at the Company’s AGM, along with a Share Purchase Plan (SPP) designed to fund plans enabling execution of the new strategy and capitalising on Zantrene’s expanded commercial potential, by pursuing the following activities: Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com
Pillar 1 – Current Zantrene, by expanding the EMD AML & FTO clinical programs, initiating a US IND, and progressing the cardio-protective opportunity.
Pillar 2 – Optimises Zantrene, with formulation development to improve utility via an improved IV formulation, oral formulation, and associated IP.
Pillar 3 – Beyond Zantrene, utilises team capabilities to pursue new RNA targeting molecules, via internal development, partnership, or acquisition.
The SPP was announced with three levels of potential funding to support an expanded FTO-targeted clinical program in solid tumours, improved formulations, a cardioprotection clinical program, new drug development, and expansion of the Phase 1b/2 EMD AML program into Europe. The SPP was launched at $3.00 per share to shareholders of record on 22 November 2021, closing 17 December 2021, with the maximum raise capped at $29.7 million. § On 8 December, Race announced an additional heart protection preclinical discovery. Zantrene was found to protect heart muscle cells from damage caused by the Multiple Myeloma drug, carfilzomib (Kyprolis) while synergising to improve anticancer effects. This cardio-protective observation broadens the formulation and potential commercial opportunities for Zantrene via the potential development of new Zantrene/carfilzomib formulations.
§ On 10 December 2021, Race announced an extension to its heart protection collaboration with the University of Newcastle. This program plans to assess Zantrene’s cardio-protective potential with additional anti-cancer drugs, where heart damage is a known treatment risk. § On 21 December 2021, Race announced raising the full $29.7 million target in a heavily oversubscribed SPP. This allows progression of the FTO solid tumour Phase 1b/2 clinical trial, cardio protective pre-clinical and clinical Phase 2b trial, expansion of the EMD AML Phase 2 trial into Europe, improved Zantrene formulations, and new molecule development. Summary of cash flow and quarterly activity As of 30 December 2021, Race held cash and equivalents of $37.10 million, compared with $8.94 million on 30 September 2021. The expansion in cash reserves reflects receipts from the SPP, exercise of options and an acceleration in research spending concurrent with expanded programs ($1.79m vs $0.93m in the prior quarter). Listing rule 4.7C.3 Payments during the quarter to Related Parties amounted to $313k, comprising payments of salaries, bonuses, and superannuation to executive directors of $270k and board fees to non-executive directors of $43k.
Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com Shareholders by holding range Race is pleased to share that shareholder numbers had increased to 9,420 on December 31, 2021, up from 9,198 on September 30, 2021, confirming continued new shareholder interest in Race’s progress.Post quarter news § On 18 January 2022, Race announced receiving its FY2021 R&D Tax refund of $708k, reflecting additional investment by Race in Australian R&D activities.
This support is an important source of non-dilutive capital and encouragement to maximise the use of Australia as a hub for research. § Post quarter, a new independent scientific publication was released in the journal Cells1, further confirming that Zantrene (bisantrene dihydrochloride) is a highly effective inhibitor of the Fat Mass and Obesity associated protein (FTO). The investigators at the University of Lille assessed the utility of Zantrene in Type 2 diabetes (T2D), a disease that is characterized by chronic high blood sugar and impaired pancreatic insulin secretion. The University of Lille team demonstrated that FTO plays a critical role in driving T2D and that inhibition of FTO by Zantrene at low concentration (100 nM); i.e. well below the level observed to cause toxicity in previous studies, increases the production of insulin by more than 20-fold from human and mouse diabetic pancreatic tissues. This third independent confirmation that Zantrene is able to target FTO2,3, this time in the pancreas, and reverse the impaired insulin secretion seen in Type 2 diabetes, is of major significance.
While further study is needed, it does emphasise the importance of FTO and m6 A dysregulation in human metabolic diseases beyond cancer.Expected news In the current quarter, shareholders can expect updates on the following activities: § Pre-clinical in vitro-updates on the progress of FTO-directed preclinical programs underway in melanoma, clear cell renal cell carcinoma and extramedullary AML. § Pre-clinical in vivo – mouse model studies are underway exploring the use of Zantrene in combination with anti-PD-1 in melanoma and in combination with decitabine for EMD AML, with results to be announced. § Clinical – Human ethics approval for EMD AML Phase 1b/2 trial. Subject to patient recruitment, an update on the AML R/R Israel trial progress, once the dose escalation phase (6-12 patients) is complete.
Management commentary Race CEO Phillip Lynch said: "The most recent quarter has been significant. We now have an entirely novel and large opportunity in cardio-protection, an evolved and strategic "Three Pillar" program and importantly the required capital and human resources to deliver against these opportunities. Thanks go to our shareholders, for their support and belief in our plans as reflected through their SPP participation" Race CSO Daniel Tillett said: "I would like to thank all the shareholders who participated in the SPP for their continued support of Race. We have been given an amazing opportunity with Zantrene, but it is one that can only be taken into the clinic with the support of our shareholders.
We are looking forward to updating our investors on the rapid progress we are making over 2022 and beyond. We are further encouraged by the newly released independent study showing Zantrene’s potential to inhibit FTO in Type 2 Diabetes. While this is not our primary area of focus, it is important in that it builds upon the original identification of Zantrene as a potent FTO inhibitor by Professor Chen and his team at the City of Hope Hospital (2020), which was later confirmed by Professor He’s team at the University of Chicago (2021).
" Race Chairman John Cullity said: "The exceptional work of our team and collaborators continues to unlock Zantrene’s potential. I’m particularly impressed by candidate clinical applications in the cardio-protection setting, which might recalibrate anthracycline therapeutics. On behalf of the Board, my particular thanks to our shareholders for supporting the recent SPP, and to Phil and Daniel for driving that process."