TEST:

DRP®-Dovitinib

"Allarity Therapeutics, Inc...is pleased to announce that the Company has been invited to give a presentation at Biomarkers Europe 2023. The presentation will focus on Allarity’s development of drug-specific DRP^® companion diagnostics (CDx) for oncology therapeutics, featuring clinical validation for several exemplary DRP^® CDx....In addition to its presentation, Allarity is honored to participate in a panel discussion titled 'Prediction Of Drug Response Using An Ex Vivo Organ Culture (EVOC) On Oncology Patients, Clinical Trial Development And Patient Testing' at the same conference."

The DRP-Dovitinib shows promise as a potential biomarker for identifying advanced RCC patients most likely to experience clinical benefit from dovitinib treatment, subject to confirmation in an independent prospective trial of dovitinib in RCC patients.

P=NA | N=135 | "Allarity Therapeutics...announced today the publication of its clinical validation of a novel drug-specific DRP®-companion diagnostic (CDx) for dovitinib in the peer-reviewed journal PLOS ONE. Data showed that the DRP®-Dovitinib CDx was able to identify a subgroup of advanced renal cell carcinoma (RCC) patients that have improved clinical benefit from treatment with dovitinib, as compared to unselected patients....In the study evaluating pre-treatment biopsies of 135 advanced RCC patients, the DRP® positive subgroup (indicating that the patient was likely to respond) (N=49) had a median overall survival of 15 months (96% CI 12.94-26.25), whereas the DRP® negative subgroup (N=86) had a median overall survival of 9.13 months (95% CI 7.49-13.2)."

"Following several weeks of analysis by Company leadership together with clinical and regulatory experts, Allarity has now filed a formal request with the FDA for a 'Type C' meeting to further discuss potential clinical paths to support approval of dovitinib, together with its DRP^®-Dovitinib companion diagnostic, in view of the FDA’s recent RTFs....The Company anticipates providing a further update on the outcome of its FDA meeting and the future of the dovitinib program before the end of the third quarter of this year."

"Allarity Therapeutics...announced that the...FDA has provided the Company with Refusal to File ('RTF') letters regarding the new drug application ('NDA') for dovitinib, and its accompanying pre-market approval ('PMA') application for the DRP®-Dovitinib companion diagnostic, for the third-line treatment of metastatic renal cell carcinoma ('mRCC'). Upon preliminary review, the FDA determined that the NDA, submitted on December 22, 2021, and the PMA application, submitted on April 2, 2021, were not sufficiently complete to permit substantive reviews....Allarity intends to seek guidance from the FDA on how to further advance dovitinib and its accompanying DRP®-Dovitinib companion diagnostic towards approval."

"Allarity Therapeutics, Inc...and Oncoheroes Biosciences, Inc...announced that they have entered into licensing agreements under which Oncoheroes will acquire exclusive, global development rights to Allarity’s therapeutic candidates dovitinib, a pan-targeted kinase inhibitor (pan-TKI), and stenoparib, a PARP inhibitor, and assume responsibility for their further clinical development in pediatric cancers...Under the terms of the licensing agreements, Oncoheroes acquires global, exclusive rights to fund and conduct further clinical development of both dovitinib and stenoparib in pediatric cancers...Allarity will support Oncoheroes’ pediatric clinical trials by providing clinical-grade drug inventory at cost and by facilitating DRP® companion diagnostic screening of pediatric patients for each drug...the Company is also planning a clinical trial of dovitnib in pediatric patients with osteosarcoma, in partnership with Oncoheroes..."

"Allarity Therapeutics, Inc...announced the submission of a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) seeking marketing approval for dovitinib for the third-line treatment of renal cell carcinoma (RCC) patients....The Company’s NDA filing is supported by its prior PMA submission with the FDA for use of Dovitinib-DRP^®, the Company’s validated companion diagnostic for the drug, to select and treat RCC patients most likely to respond to dovitinib."

The DRP-Dovitinib can be used as a predictive biomarker and thus as a tool for the physician in identifying advanced RCC patients most likely to experiencing clinical benefit from dovitinib treatment.

Pathway/process Genes FGF SEL1L3 LSM4 STAT6 - GATA3 VEGF VEGFA FABP5 DPP4 LDLR TMSB10 P4HA1 STAT6 RPL38 - HRAS UCP2 ATM GATA3 SPDEF CUL3 PDGF STAT6 UCP2 - TUG1 ATM GATA3 PI3K/Akt/mTOR REDD1 TRIM22 FABP5 MCT4 INSIG1 - HRAS SCAMP3 IGFBP5 ATM SRM CUL3 Drug resistance ABCF1 IGFBP5 Metastasis and hypoxia DPP4 REDD1 - ATM NDUFV1 CERS 2 CKB Topoisomerase HRAS APITD1 Other RPS20 TPK1 MIR196B HSPE1 CAV2 APOL1 PTPRE DPYSL2 ANP32B RPL27A EPB41L2 RPL3 - BAG5 BAG6 MARCH6 EMC3 CLPTM1 MAGEA1 LDOC1 ZNF331 TOB1 NDUFV1 MCUR1 NBPF10 PPP1R11 Pi3K/Akt/mTOR is downstream of FLT3, c-KIT and PDGFRA Conclusion The DRP-Dovitinib biomarker confirms many of the pathways known to be targeted by dovitinib, but also proposes novel mechanisms of resistance, such as ABC transporter F1. The DRP-Dovitinib is currently being employed in retrospective and prospective clinical trials with dovitinib.

Pathway/process Genes FGF SEL1L3 LSM4 STAT6 - GATA3 VEGF VEGFA FABP5 DPP4 LDLR TMSB10 P4HA1 STAT6 RPL38 - HRAS UCP2 ATM GATA3 SPDEF CUL3 PDGF STAT6 UCP2 - TUG1 ATM GATA3 PI3K/Akt/mTOR REDD1 TRIM22 FABP5 MCT4 INSIG1 - HRAS SCAMP3 IGFBP5 ATM SRM CUL3 Drug resistance ABCF1 IGFBP5 Metastasis and hypoxia DPP4 REDD1 - ATM NDUFV1 CERS 2 CKB Topoisomerase HRAS APITD1 Other RPS20 TPK1 MIR196B HSPE1 CAV2 APOL1 PTPRE DPYSL2 ANP32B RPL27A EPB41L2 RPL3 - BAG5 BAG6 MARCH6 EMC3 CLPTM1 MAGEA1 LDOC1 ZNF331 TOB1 NDUFV1 MCUR1 NBPF10 PPP1R11 Pi3K/Akt/mTOR is downstream of FLT3, c-KIT and PDGFRA Conclusion The DRP-Dovitinib biomarker confirms many of the pathways known to be targeted by dovitinib, but also proposes novel mechanisms of resistance, such as ABC transporter F1. The DRP-Dovitinib is currently being employed in retrospective and prospective clinical trials with dovitinib.

Pathway/process Genes FGF SEL1L3 LSM4 STAT6 - GATA3 VEGF VEGFA FABP5 DPP4 LDLR TMSB10 P4HA1 STAT6 RPL38 - HRAS UCP2 ATM GATA3 SPDEF CUL3 PDGF STAT6 UCP2 - TUG1 ATM GATA3 PI3K/Akt/mTOR REDD1 TRIM22 FABP5 MCT4 INSIG1 - HRAS SCAMP3 IGFBP5 ATM SRM CUL3 Drug resistance ABCF1 IGFBP5 Metastasis and hypoxia DPP4 REDD1 - ATM NDUFV1 CERS 2 CKB Topoisomerase HRAS APITD1 Other RPS20 TPK1 MIR196B HSPE1 CAV2 APOL1 PTPRE DPYSL2 ANP32B RPL27A EPB41L2 RPL3 - BAG5 BAG6 MARCH6 EMC3 CLPTM1 MAGEA1 LDOC1 ZNF331 TOB1 NDUFV1 MCUR1 NBPF10 PPP1R11 Pi3K/Akt/mTOR is downstream of FLT3, c-KIT and PDGFRA Conclusion The DRP-Dovitinib biomarker confirms many of the pathways known to be targeted by dovitinib, but also proposes novel mechanisms of resistance, such as ABC transporter F1. The DRP-Dovitinib is currently being employed in retrospective and prospective clinical trials with dovitinib.

Pathway/process Genes FGF SEL1L3 LSM4 STAT6 - GATA3 VEGF VEGFA FABP5 DPP4 LDLR TMSB10 P4HA1 STAT6 RPL38 - HRAS UCP2 ATM GATA3 SPDEF CUL3 PDGF STAT6 UCP2 - TUG1 ATM GATA3 PI3K/Akt/mTOR REDD1 TRIM22 FABP5 MCT4 INSIG1 - HRAS SCAMP3 IGFBP5 ATM SRM CUL3 Drug resistance ABCF1 IGFBP5 Metastasis and hypoxia DPP4 REDD1 - ATM NDUFV1 CERS 2 CKB Topoisomerase HRAS APITD1 Other RPS20 TPK1 MIR196B HSPE1 CAV2 APOL1 PTPRE DPYSL2 ANP32B RPL27A EPB41L2 RPL3 - BAG5 BAG6 MARCH6 EMC3 CLPTM1 MAGEA1 LDOC1 ZNF331 TOB1 NDUFV1 MCUR1 NBPF10 PPP1R11 Pi3K/Akt/mTOR is downstream of FLT3, c-KIT and PDGFRA Conclusion The DRP-Dovitinib biomarker confirms many of the pathways known to be targeted by dovitinib, but also proposes novel mechanisms of resistance, such as ABC transporter F1. The DRP-Dovitinib is currently being employed in retrospective and prospective clinical trials with dovitinib.