On March 14, 2019 AVEO Oncology (NASDAQ: AVEO) reported financial results for the full year ended December 31, 2018 and provided a business update (Press release, AVEO, MAR 14, 2019, View Source [SID1234534330]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer"

Tweet this
"The results of TIVO-3, presented in February at the 2019 ASCO (Free ASCO Whitepaper) GU Symposium, underscore a unique activity and tolerability profile among VEGF TKIs in the treatment of kidney cancer," said Michael Bailey, president and chief executive officer of AVEO. "We continue to believe that there is a significant potential commercial opportunity for an active and well tolerated therapy within the third plus line of therapy, particularly one that demonstrated activity in a highly refractory patient population that has received prior PD-1 treatment. We are hopeful that the positive PFS outcomes from TIVO-3 translate into an improved overall survival hazard ratio and look forward to reporting a more mature interim OS outcome in the fourth quarter of 2019."

Recent Highlights

Presented Topline Results from TIVO-3 During an Oral Presentation at the 2019 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium. In February 2019, AVEO presented topline results from the TIVO-3 trial, AVEO’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in 350 subjects with refractory advanced or metastatic renal cell carcinoma (RCC) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium held February 14-16, 2019 in San Francisco. The results were presented during an oral presentation titled "TIVO-3: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC)." A copy of the presentation is currently available in the Publications & Presentation section of AVEO’s website.

The presentation noted that the TIVO-3 trial met its primary endpoint of demonstrating a statistically significant benefit in median progression-free survival (PFS). Median PFS for tivozanib was also longer than sorafenib both in patients who received prior PD-1 therapy and those who received two prior VEGF TKI therapies. The secondary endpoint of overall response rate also demonstrated a statistically significant improvement for patients receiving tivozanib compared to sorafenib.

The analysis of the secondary endpoint of overall survival (OS) was not mature at the time of the final PFS analysis. As presented, the preliminary OS analysis conducted at an October 4, 2018 data cutoff date, which included additional patients previously lost to follow-up, showed a non-statistically significant difference in OS favoring sorafenib (hazard ratio: 1.12, p-value: 0.44).

Tivozanib was generally well-tolerated relative to sorafenib, with reported grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. The improved tolerability of tivozanib was evident in the lower rates of dose reductions and interruptions for toxicity in patients receiving tivozanib compared to those receiving sorafenib. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.
Announced NDA Timing Update. In January 2019, the U.S. Food and Drug Administration (FDA) recommended that AVEO not submit a New Drug Application (NDA) for tivozanib at this time using the preliminary OS results from the TIVO-3 trial. The FDA indicated that these preliminary OS results do not allay their concerns about the potential detriment in OS outlined in the Complete Response Letter dated June 6, 2013. AVEO now plans to make an NDA filing decision following the availability of more mature OS results. AVEO intends to conduct an additional interim OS analysis in August 2019, the results of which are expected to be reported in the fourth quarter of 2019.
Data from Phase 1b Expansion Cohort of Ficlatuzumab and Cytarabine in Relapsed and Refractory AML to be Presented at 2019 AACR (Free AACR Whitepaper) Annual Meeting. Data from the investigator-sponsored Phase 1b expansion cohort evaluating the safety and tolerability of ficlatuzumab, AVEO’s potent hepatocyte growth factor (HGF) inhibitory antibody, in combination with cytarabine in patients with relapsed and refractory acute myeloid leukemia (AML) will be presented during a poster session at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The presentation, titled, "Cyfi: Results from a Phase 1b expansion cohort of anti-hepatocyte growth factor and cytarabine in relapsed and refractory AML" (abstract CT078 / 2) will be featured during a poster session (Session PO.CT03) on Monday, April 1, 2019 from 1:00-5:00pm Eastern Time.
Entered Immuno-Oncology Clinical Supply Agreement with AstraZeneca. In December 2018, AVEO entered into a clinical supply agreement with AstraZeneca to evaluate the safety and efficacy of AstraZeneca’s IMFINZI (durvalumab), a human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in combination with tivozanib in first-line hepatocellular carcinoma, or liver cancer, in a Phase 1/2 study. AVEO will serve as the study sponsor; each party will contribute the clinical supply of its study drug and study costs will be otherwise shared equally. The Phase 1 portion of the study is expected to commence this year.
Earned $2 Million Milestone Payment from EUSA Pharma. In November 2018, AVEO announced the triggering of a $2 million milestone payment from EUSA Pharma related to the reimbursement in Germany for FOTIVDA as a first line treatment of adult patients with advanced RCC.
Extended Debt Facility Interest-Only Period. In December 2018, AVEO announced a six-month extension to the interest-only period under its existing amended and restated loan and security agreement with Hercules Capital, Inc. The extension was granted as a result of achieving certain predefined requirements under the agreement, including successfully meeting the primary endpoint of the TIVO-3 trial.
Raised $7.5 Million Under the Sales Agreement with SVB Leerink, Extending Financial Runway. In February 2019, AVEO raised $7.5 million through its sales agreement with SVB Leerink. Approximately $32 million of shares remain available for future issuance and sale pursuant to the sales agreement, which was originally entered into in February 2018. AVEO believes that the proceeds generated in February 2019 through the sales agreement, together with its available cash, cash equivalents, and marketable securities at December 31, 2018, and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, will allow it to fund planned operations into the first quarter of 2020.
Full Year 2018 Financial Highlights

AVEO ended 2018 with $24.4 million in cash, cash equivalents and marketable securities as compared with $33.5 million at December 31, 2017.
Total revenue for 2018 was approximately $5.4 million compared with $7.6 million for 2017.
Research and development expense for 2018 was $20.7 million compared with $25.2 million for 2017.
General and administrative expense for 2018 was $10.8 million compared with $9.1 million for 2017.
Net loss for 2018 was $5.3 million, or a loss of $0.04 and $0.19 per basic and diluted share, respectively, compared with a net loss of $65.0 million for 2017, or a loss of $0.61 per basic and diluted share.
The 2018 net loss was partially offset by an approximate $19.9 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from the decrease in the stock price that occurred within the fiscal year. In 2017, the non-cash loss attributable to the increase in the fair value of such warrant liability was $33.7 million.
Financial Guidance

AVEO believes that its $24.4 million in cash, cash equivalents, and marketable securities at the end of 2018, together with the additional $7.5 million raised from sales under its sales agreement with SVB Leerink in February 2019 and together with the extension of the interest-only period under the Hercules loan agreement, which results in deferment of principal payments, would allow it to fund planned operations into the first quarter of 2020. This estimate assumes no receipt of additional milestones from AVEO’s partners, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of outstanding warrants issued in connection with the 2016 private placement or outstanding warrants issued in connection with the recent settlement of the securities class action litigation.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal and breast cancers. In addition, a new formulation of tivozanib is in pre-clinical development for the treatment of age-related macular degeneration.

On March 14, 2019 Novelion Therapeutics Inc. (NASDAQ: NVLN), a biopharmaceutical company dedicated to developing and commercializing therapies for individuals living with rare diseases ("Novelion" or the "Company"), today reported financial results for the fourth quarter and year ended December 31, 2018 (Press release, QLT, MAR 14, 2019, View Source [SID1234534329]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Novelion’s Interim Chief Executive Officer Ben Harshbarger commented, "We are pleased with our fourth quarter results which reflect strong revenue performance and show meaningful impact from the cost reduction initiatives executed throughout 2018. We remain focused on undertaking a comprehensive capital restructuring and also on delivering our two very important rare disease therapies to indicated patients in need."

Business Update

Following marketing authorization of MYALEPTA (metreleptin) for generalized lipodystrophy (GL) and partial lipodystrophy (PL) by the EMA in July, our subsidiary Aegerion Pharmaceuticals commenced the pricing and reimbursement processes in key EU markets. Reimbursement decisions in many of the key EU markets are anticipated throughout 2019. MYALEPTA sales growth in 2018 was supported by named patient sales programs, which allow for sales on an unsolicited basis prior to regulatory approval and/or pricing and reimbursement decisions, as well as the launch of MYALEPTA in Germany in the fourth quarter.

In February 2019, Aegerion entered into an exclusive licensing agreement with Recordati Rare Diseases Inc. ("Recordati") for the commercialization of JUXTAPID (lomitapide) in Japan. The agreement includes exclusive rights in Japan for Recordati to commercialize JUXTAPID for the current approved indication, homozygous familial hypercholesterolemia (HoFH). The terms of, and use of proceeds from, the Recordati licensing agreement are described more fully in Novelion’s Form 8-K filed on February 6, 2019.

In January 2019, Aegerion held a meeting with the U.S. Food and Drug Administration (FDA) to obtain feedback on the design of the placebo-controlled study that will be required in order to pursue the PL indication for MYALEPT in the U.S. The Company is assessing feedback on the study design and integrating it into the Phase 3 study protocol.

Aegerion plans to file for regulatory approvals for metreleptin in GL and PL in certain key markets outside the U.S. and EU, including Brazil, in 2019.

As previously announced, Novelion and Aegerion have each engaged advisors to independently explore and advise them on all available strategic alternatives regarding the Company’s capital structure, such as a restructuring of Aegerion’s Convertible Notes due August 2019 (including a restructuring that would likely involve a debt for equity swap), a sale or merger of Novelion or Aegerion, or the sale or other disposition of certain businesses or assets. The implementation of one or more of such transactions (or the failure to complete any such transaction or transactions) will likely require Aegerion, and could require Novelion, to seek the protections of applicable bankruptcy laws allowing for corporations to seek to restructure their debts and other affairs under a reorganization.
Fourth Quarter 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $15.2 million in the fourth quarter of 2018, compared to $20.1 million for the same period in 2017, $8.2 million, or 53.9%, of which was from prescriptions written in the U.S. and $0.8 million of which was royalty revenue from sales of JUXTAPID in the EMEA region. The JUXTAPID revenue decline in the fourth quarter of 2018 compared to the same period in 2017 was primarily due to product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy.

MYALEPT: Novelion reported net revenues of MYALEPT of $25.5 million in the fourth quarter of 2018, compared to $18.8 million for the same period in 2017, $13.4 million, or 52.5%, of which was from prescriptions written in the U.S. MYALEPT revenue growth in the fourth quarter was driven by increased sales in all key markets.

GAAP total net revenues for the fourth quarter of 2018 were $40.7 million compared to $38.9 million for the same period in 2017.

Cost of product sales for the fourth quarter of 2018 was $18.0 million compared to $17.0 million for the same period in 2017, resulting in stable year-over-year fourth quarter gross margins.

GAAP total operating expenses for the fourth quarter of 2018 were $21.7 million compared to total operating expenses of $35.9 million, a 39.6% reduction compared to the same period in 2017. GAAP SG&A expenses were $14.1 million in the fourth quarter of 2018 compared to $24.1 million for the same period in 2017. GAAP R&D expenses were $7.7 million in the fourth quarter of 2018 compared to $11.8 million for the same period in 2017.

On a non-GAAP basis, during the fourth quarter of 2018, SG&A expenses were $13.0 million compared to $22.5 million for the same period in 2017. The 42.2% decrease in non-GAAP SG&A expenses in the fourth quarter of 2018 compared with the same period in 2017 was primarily related to cost reduction initiatives executed throughout 2018.

On a non-GAAP basis, during the fourth quarter of 2018, R&D expenses decreased 33.6% to $7.7 million compared to $11.6 million for the same period in 2017, reflecting cost reduction initiatives executed throughout 2018.

GAAP net loss in the fourth quarter of 2018 was $19.4 million, an improvement of approximately 21.1% compared to GAAP net loss of $24.6 million during the same period in 2017.

On a non-GAAP basis, net income was $2.9 million in the fourth quarter of 2018 compared to a net loss of $3.3 million for the same period in 2017.

A full reconciliation of the GAAP financial results to non-GAAP financial results is included in the financial information tables below.

Full Year 2018 Financial Results

JUXTAPID: Novelion reported net revenues of JUXTAPID of $59.1 million for the year ended December 31, 2018, compared to $72.1 million for 2017. The decline in sales resulted from product competition for JUXTAPID, restrictions on reimbursement, and patient discontinuation from therapy. Named patient sales of JUXTAPID in Brazil totaled $0.4 million in 2018, compared to $6.7 million of JUXTAPID named patient sales in Brazil in 2017. Revenue growth in Japan in 2018 helped offset the sales decline in the U.S. and Brazil.

MYALEPT: Novelion reported net revenues of MYALEPT of $71.4 million for the year ended December 31, 2018, compared to $66.3 million for 2017. The increase was primarily attributable to revenues in France, Germany and Turkey. In addition, 2017 MYALEPT sales benefited from $2.3 million of one-time deferred revenue recognition in the U.S.

GAAP total net revenues for the year ended December 31, 2018 were $130.4 million compared to $138.4 million for 2017.

Cost of product sales for the year ended December 31, 2018 was $59.7 million compared to $77.2 million for 2017, resulting in improved gross margin. The improvement in 2018 was primarily a result of higher reserves in 2017 for excess and obsolete inventory which were charged to cost of product sales, partially offset by a higher royalty rate on U.S. sales of metreleptin in 2018.

GAAP total operating expenses for the year ended December 31, 2018 were $120.8 million compared to total operating expenses of $148.0 million for 2017. GAAP SG&A expenses were $79.8 million for the year ended December 31, 2018 compared to $96.5 million for 2017. GAAP R&D expenses were $38.8 million for the year ended December 31, 2018 compared to $49.0 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, SG&A expenses decreased 20.0% to $72.6 million compared to $90.7 million for 2017, primarily as a result of cost reduction initiatives executed throughout 2018. Restructuring charges for 2018 were $2.2 million, compared with restructuring charges of $2.5 million for 2017.

On a non-GAAP basis, for the year ended December 31, 2018, R&D expenses decreased 20.5% to $38.3 million compared to $48.2 million for 2017 due primarily to cost reduction initiatives executed throughout 2018.

GAAP net loss for the year ended December 31, 2018 was $108.3 million compared to GAAP net loss of $126.7 million for 2017.

Net loss on a non-GAAP basis for the year ended December 31, 2018 was $25.3 million, compared to $30.0 million for 2017.

As of December 31, 2018, the Company’s consolidated unrestricted cash balance was $45.2 million, compared to $55.4 million at December 31, 2017. Novelion’s consolidated cash as of December 31, 2018 includes $13.3 million at Novelion and $31.9 million at the Aegerion subsidiary level.

Debt and Government Settlement Payments

As of December 31, 2018, Aegerion’s debt liabilities and government settlement payments included $302.5 million in outstanding principal under Aegerion’s Convertible Notes due August 15, 2019, $75.9 million in outstanding principal (including paid in kind fees and interest) under Aegerion’s secured term loans having a maturity date of June 30, 2019, $37.1 million outstanding under Aegerion’s secured intercompany term loan with Novelion, as lender, which has a maturity date of July 1, 2019 (which term loan amounts were subsequently reduced by repayments received from the Recordati license transaction described above), as well as $31.1 million owed under Aegerion’s settlements with the Department of Justice and the U.S. Securities and Exchange Commission (the "Commission"), payable in prescribed installments until the first quarter of 2021.

Financial Guidance

Novelion expects total net revenues in 2019 to be between $160.0 and $175.0 million, including $30.0 million of licensing revenues, in the form of the $25.0 million upfront licensing payment and $5.0 payment upon transfer of the marketing authorization to Recordati, resulting from the Recordati transaction.

On March 14, 2019 AstraZeneca will share pioneering research and development across its successful Oncology portfolio and extensive next-generation pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, USA, 29 March to 3 April 2019 (Press release, AstraZeneca, MAR 14, 2019, View Source [SID1234534328]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The new research will showcase AstraZeneca’s potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, taking the DNA Damage Response (DDR) pipeline beyond PARP inhibition. Additional highlights include new insights from the MYSTIC and TATTON trials for Imfinzi (durvalumab) and Tagrisso (osimertinib) in predicting response and addressing treatment resistance in lung cancer.

In total, data from 84 presentations will illustrate the progress of AstraZeneca’s Oncology pipeline, with 28 abstracts reporting new Immuno-Oncology (IO) data, 33 focused on complementary biological pathways exploring the DDR mechanism, and 20 on tumour drivers and resistance mechanisms.

José Baselga, Executive Vice President, Research & Development, Oncology, said: "AstraZeneca is continuing to strengthen its portfolio of innovative cancer medicines by exploring new indications and developing a pioneering next-generation pipeline. We will be sharing some of our latest research at the 2019 AACR (Free AACR Whitepaper) Annual Meeting, including 28 new molecular entities and six combinations, highlighting an exciting new phase of scientific discovery from our Oncology R&D."

IO pipeline explores new pathways to enhance immune response

Key data from AstraZeneca’s early-stage clinical and preclinical IO pipeline include potential new medicines targeting multiple pathways, providing insight into novel mechanisms to boost current immune response and modify the tumour microenvironment both alone and in combination with checkpoint inhibition.

Presentations will highlight AstraZeneca’s growing portfolio in small molecules and antisense oligonucleotides (ASOs) targeting immunosuppressive mechanisms in cancer, and the Company’s exploration of the adenosine pathway, which is increasingly recognised as critical to tumour suppression and represents a new frontier within IO.

Phase I and preclinical data demonstrating AZD4635, a small molecule A2AR antagonist, prevents adenosine-mediated immunosuppression. Early clinical activity has been observed with AZD4635 monotherapy or in combination with Imfinzi in patients with metastatic castration-resistant prostate cancer (Abstracts #LB-192/10, #CT026/21)
Preclinical research on the activity of ASO AZD8701 (ION-AZ7), showing that inhibiting FOXP3 may limit immunosuppressive functions and induce tumour regression (Abstract #2713)
Preclinical pharmacodynamic and mechanistic data illustrating how danvatirsen (AZD9150), a STAT3 ASO reverses immunosuppression to produce significant anti-tumour effects, both as monotherapy and in combination with anti-PDL1 (Abstract #3215/25)
Preclinical data for MEDI5083, a novel fusion protein which activates the CD40 pathway, indicating robust immune activation and anti-tumour activity (Abstract #1534/3)
Preclinical data for MEDI1191, a novel IL12-based treatment designed for injection directly into tumours, showing potential to drive anti-tumour response for patients with solid tumours both as monotherapy and in combination with anti-PDL1 (Abstract #5017/11)
Next wave of DDR targets

New research will showcase AstraZeneca’s DDR pipeline beyond PARP inhibition, including on the discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor (Abstract #DDT01-02). DNA-PK is critical in repairing DNA double strand breaks through the non-homologous end joining (NHEJ) pathway and has also been linked to the replication stress response (RSR), a type of DDR.

Additional new data will be shared on reversing PARP inhibitor resistance by targeting alternative DDR dependencies, like the RSR (Abstract #932).

Predicting response and addressing treatment resistance in lung cancer: new insights from MYSTIC and TATTON trials for Imfinzi and Tagrisso

Exploratory analyses of blood and tissue tumour mutational burden (TMB) from the Phase III MYSTIC trial assess TMB as a potential biomarker of survival in 1st-line use of Imfinzi with or without tremelimumab vs. chemotherapy in metastatic non-small cell lung cancer (NSCLC) (Abstract #CT074). The trial did not meet the primary endpoints, but Imfinzi monotherapy demonstrated clinical activity in the primary analysis. The MYSTIC trial provides the most comprehensive data set to date evaluating blood TMB and is the only Phase III randomised, controlled trial to demonstrate an association between high TMB and overall survival benefit with immunotherapy treatment. This new analysis will further evaluate the use of TMB as a potential biomarker predictive of survival benefit with IO treatment.

In addition, several abstracts will be presented from the TATTON Phase Ib trial testing the combination of Tagrisso with potential new medicines savolitinib or selumetinib in NSCLC patients who have progressed on prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment (Abstracts #CT032, #CT033, #CT034). The TATTON trial supports SAVANNAH, an ongoing Phase II clinical trial exploring the combination of Tagrisso and savolitinib to overcome MET-driven EGFR-TKI resistance following treatment with Tagrisso in EGFR-mutated (EGFRm) NSCLC. Characterisation of detection methods for identifying MET-driven EGFR-TKI resistance will be presented (Abstract #4897/20). TATTON will also inform the trial design of ORCHARD, a Phase II platform trial exploring potential new treatment options to address resistance mechanisms in patients with EGFRm NSCLC who have experienced disease progression following 1st-line treatment with Tagrisso.

Key AstraZeneca presentations at AACR (Free AACR Whitepaper) 2019

Lead author

Abstract title

Presentation details

Immuno-Oncology

Peters, S

Tumour mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a Phase 3 study of first-line durvalumab ± tremelimumab vs chemotherapy

Abstract #CT074

Session CTPL03 – Optimizing PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy: Dedicated to the Memory of Waun Ki Hong

Monday 1 April

10:30am-12:45pm

Marcus Auditorium- Bldg A-GWCC

Srinivasan, S

STAT3 ASO reverses immunosuppression and enhances cytotoxic cell function to enhance PDL1 blockade

Abstract #3215/25

Session PO.IM02.01 – Combination Immunotherapies 2

Tuesday 2 April

8:00am-12:00pm

Section 23

Barbon, CM

The A2AR antagonist AZD4635 prevents adenosine-mediated immunosuppression of CD103+ dendritic cells

Abstract #LB-192/10

Session LBPO.IM02 – Late-Breaking Research:
Immunology 2

Tuesday 2 April

8:00am-12:00pm

Section 42

Merchant, MS

Evidence of Immune Activation in the first-in-human Phase 1a dose escalation study of the Adenosine 2a Receptor Antagonist, AZD4635, in patients with advanced solid tumors

Abstract #CT026/21

Session PO.CT01 – Phase I Clinical Trials: Part 1

Sunday 31 March

1:00pm-5:00pm

Section 16

Sinclair, C

Discovery and characterization of AZD8701, a high affinity antisense oligonucleotide targeting FOXP3 to relieve immunosuppression in cancer

Abstract #2713

Session MS.IM02.01 – Rational Combinations of Immunotherapy

Monday 1 April

4:35pm-4:50pm

Room A411-Georgia World CC

Wang, Y

MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen presenting cells and promotes a robust anti-tumor immune response in a B16F10 murine tumor model

Abstract #1534/3

Session PO.IM02.17 – Therapeutic Antibodies 2

Monday 1 April

8:00am-12:00pm

Section 25

Luheshi, N

MEDI1191, a novel IL-12 mRNA therapy for intratumoral injection to promote TH1 transformation of the patient tumor microenvironment

Abstract #5017/11

Session PO.IM02.10 – Tumor Immune Microenvironment

Wednesday 3 April

8:00am-12:00pm

Section 25

DNA damage response

Goldberg, FW

Discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor

Abstract #DDT01-02

Session DDT01 – New Drugs on the Horizon: Part 1

Sunday 31 March

1:24pm-1:48pm

Room A305 – Georgia World CC

Cadogan, EB

AZD7648: A potent and selective inhibitor of DNA-PK with pharmacodynamic and monotherapy anti-tumour activity

Abstract #3505/16

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

Fok, J

AZD7648, a potent and selective inhibitor of DNA-PK, potentiates the activity of ionising radiation and doxorubicin in vitro and causes tumour regression in xenograft models

Abstract #3512/23

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

O’Connor, M

Reversing PARP inhibitor resistance by targeting the replication stress response

Abstract #932

Session MS.ET03.01 – Drug Resistance

Sunday 31 March

4:35pm-4:50pm

Room B304 – Georgia World CC

Tumour drivers and resistance

Yu, H

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT032

Session CTPL02 – Can the Challenge of NSCLC Resistance be MET or Will We Not MEK It?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Sequist, L

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT033

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Ramalingam, S

Osimertinib plus selumetinib for patients (pts) with EGFR-mutant (EGFRm) NSCLC following disease progression on an EGFR-TKI: results from the Phase Ib TATTON study

Abstract #CT034

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Hartmaier, RJ

Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study

Abstract #4897/20

Session PO.CL11.07 – Novel Strategies for Biomarker Identification and Use in Cancer 3

Wednesday 3 April

8:00am-12:00pm

Section 19

Liquid biopsies

Barrett, JC

Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Major Symposium: Regulatory Science and Policy

Session SYPOL07 – Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Tuesday 2 April

3:00pm-5:00pm

Room A402 – Georgia World CC

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On March 14, 2019 ESSA Pharma Inc. (TSX-V: EPI;Nasdaq: EPIX) ("ESSA" or the "Company"), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer reported that the Company will be attending the 31st Annual ROTH Conference to be held on March 17 -19 at the Ritz Carlton Laguna Niguel in Dana Point, California (Press release, ESSA, MAR 14, 2019, View Source [SID1234534324]). Dr. David R. Parkinson, President & Chief Executive Officer and Peter Virsik, Chief Operating Officer will be available for one-on-one meetings throughout the conference.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On March 14, 2019 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for selinexor (Press release, Karyopharm, MAR 14, 2019, View Source [SID1234534323]). The NDA, which is currently under Priority Review by the FDA, is seeking accelerated approval for selinexor in combination with dexamethasone for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. The previously disclosed April 6, 2019 PDUFA date has been extended by three months to July 6, 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On February 26, 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) met to discuss the selinexor NDA and voted 8 to 5 recommending that the FDA wait for the results from Karyopharm’s randomized, open-label, Phase 3 BOSTON study evaluating selinexor in patients with relapsed or refractory multiple myeloma, before making a final decision regarding approval. Although the FDA considers the recommendation of this panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.

Following the ODAC meeting, at the FDA’s request, Karyopharm submitted additional, existing clinical information as an amendment to the NDA, which allowed the FDA to extend the PDUFA action date by three months. "We look forward to the continued collaboration with FDA in trying to meet the needs of patients with relapsed refractory multiple myeloma," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm.

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with triple class refractory multiple myeloma. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval and was granted accelerated assessment. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.