Stemline Therapeutics Announces Positive Clinical Data from ELZONRISTM (tagraxofusp; SL-401) Trials in BPDCN, CMML and MF Delivered at the EHA Congress

On June 18, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that positive clinical data from ELZONRISTM (tagraxofusp; SL-401) trials were presented at the 23rdCongress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden (Press release, Stemline Therapeutics, JUN 18, 2018, View Source [SID1234527374]).

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Results from the completed pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) were presented for the first time to a European audience. This oral presentation also included positive survival and safety updates. Updated results from ongoing clinical trials in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML) or relapsed/refractory myelofibrosis (MF) were also presented and continue to indicate the potential of ELZONRIS in indications beyond BPDCN.

Copies of all three presentations are available on Stemline’s website (www.stemline.com) under the Scientific Presentations tab.

Highlights from the Pivotal Trial – BPDCN (ELZONRIS 5-day regimen, multicycle)

ELZONRIS demonstrated high response rates and high rate of stem cell transplant (SCT) in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
° 90% overall response rate (ORR) in first-line (12 mg/kg; n=29); 69% ORR in relapsed/refractory (n=13)
• Majority of responses are complete responses
° 45% of patients treated with ELZONRIS in first-line (12 mg/kg) were bridged to stem cell transplant in remission (n=13)
No apparent cumulative adverse events, including in the bone marrow, over multiple cycles
Updated data: Median overall survival (OS) in first-line (12 mg/kg; n=29) not reached
Rolling BLA submission in BPDCN underway; on track for completion this quarter
Highlights from the CMML Phase 1/2 Trial (ELZONRIS 3-day regimen, multi-cycle)

ELZONRIS monotherapy demonstrated efficacy, including bone marrow complete responses and improvements in splenomegaly, with a manageable safety profile in patients with relapsed/refractory CMML, an area of high unmet medical need
° Patient enrollment and follow up continues
Manageable safety profile
° Most common treatment-related adverse events (TRAEs) included hypoalbuminemia (38%), thrombocytopenia (25%), and fatigue (25%). Most common TRAEs, grade 3+, include thrombocytopenia (25%) and nausea (6%)
2 bone marrow complete responses (BMCRs)
100% of evaluable patients had reduction in baseline splenomegaly (spleen response)
° 75% had reduction by ≥50%
° 60% with baseline spleen size ≥5cm had reduction by ≥50%
55% (6/11) evaluable patients with treatment duration 6+ months, including 8+ and 14+ months
Based on these encouraging results, registrational trial designs in patients with relapsed/refractory CMML are under evaluation
Highlights from the MF Phase 1/2 Trial (ELZONRIS 3-day regimen, multi-cycle)

ELZONRIS monotherapy demonstrated efficacy, namely improvements in splenomegaly, with a manageable safety profile, in patients with relapsed/refractory MF, an area of high unmet medical need
° Patient enrollment and follow up continues
Manageable safety profile
° Most common TRAEs include hypoalbuminemia and thrombocytopenia (each 27%), and alanine aminotransferase increased, anemia, dizziness, fatigue, headache and nausea (each 20%). Most common TRAEs, grade 3+, include anemia (20%) and thrombocytopenia and fatigue (each 7%)
50% of evaluable patients, with baseline spleen size ≥5cm, had reduction in baseline splenomegaly
° 33% had reduction by ≥33%
° 25% had reduction by ≥35%
67% (6/11) of patients with spleen response had treatment duration 8+ months, including 8+, 12+ and 14+ months (all 3 ongoing)
° 4 patients with baseline thrombocytopenia had treatment durations 8+ months, 3 ongoing
Initial Quality of Life assessments appear promising, and a full TSS (Total Symptom Score) analysis is ongoing
Based on these encouraging results, next steps for the program are being evaluated including single agent, combination, and registration-directed trials in patients with relapsed/refractory MF
Ivan Bergstein, M.D., Stemline’s CEO, commented, "We had another strong showing at a major oncology conference. Our ELZRONRIS pivotal data in BPDCN, which included positive updates around survival and safety, were showcased and very well-received at EHA (Free EHA Whitepaper). The completion of our rolling BLA submission remains on-track for this quarter, and we continue to aggressively advance our pre-launch activities." Dr. Bergstein continued, "Additionally, given the encouraging data we continue to see with ELZONRIS in patients with previously-treated CMML and previously-treated MF, we are actively evaluating registrational opportunities in these areas of unmet medical need."

About ELZONRISTM (tagraxofusp; SL-401)
ELZONRISTM (tagraxofusp; SL-401) is a novel targeted therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. ELZONRIS has successfully completed a pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an indication for which it was granted Breakthrough Therapy Designation (BTD). A rolling Biologics License Application (BLA) submission is underway. ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

Myriad’s BRACAnalysis CDx® Supplementary PMA Accepted by FDA for Review as a Companion Diagnostic for Talazoparib in Metastatic Breast Cancer

On June 18, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that the U.S. Food and Drug Administration (FDA) has accepted its supplementary premarket approval (sPMA) application for BRACAnalysis CDx to be used as a companion diagnostic with Pfizer’s PARP (poly ADP ribose polymerase) inhibitor, talazoparib (Press release, Myriad Genetics, JUN 18, 2018, View Source [SID1234527373]). The New Drug Application (NDA) for talazoparib has been granted priority review by the U.S. Food and Drug Administration and has a Prescription Drug User Fee Act (PDUFA) goal date of December 2018.

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Myriad’s sPMA and Pfizer’s NDA submissions are based on results from the Pfizer-sponsored EMBRACA trial, which evaluated talazoparib versus chemotherapy in patients with germline (inherited) BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer (MBC). The primary results of the study were presented at the San Antonio Breast Cancer Symposium in December 2017.

"Myriad was the pioneer in developing companion diagnostics for PARP inhibitors and this submission is another milestone in our collaborations to expand access to this class of drugs across multiple cancers," said Mark C. Capone, president and CEO, Myriad Genetics. "We are excited to pursue a simultaneous diagnostic approval along with talazoparib, as another outstanding opportunity to advance personalized medicine for oncology patients."

Myriad estimates there are approximately 125,000 patients with metastatic breast cancer who would immediately qualify for the BRACAnalysis CDx test, followed by 60,000 new patients per year on an ongoing basis.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying cancer patients with deleterious or suspected deleterious germline BRCA variants who may be candidates for a PARP inhibitor. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

BioLineRx Presents New Overall Survival Data From Phase 2a Study for BL-8040 in r/r AML Patients

On June 18, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that new data presented at the 23rd Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), held in Stockholm, Sweden, shows that BL-8040, combined with high dose cytarabine (HiDAC), significantly enhanced overall survival in difficult-to-treat relapsed or refractory AML (r/r AML) patients in a Phase 2a clinical trial (Press release, BioLineRx, JUN 18, 2018, View Source;p=RssLanding&cat=news&id=2354886 [SID1234527372]). In addition, an important new finding shows a statistically significant correlation between patient response and the mobilization of AML blasts. Responding patients demonstrated a clear and significant increase in the number of AML blasts in the peripheral blood following BL-8040 treatment, whereas non-responding patients were largely unaffected.

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"We are extremely pleased to see further significant improvement in overall survival for this very difficult-to-treat patient population, as data continues to accumulate from our Phase 2a proof-of-concept study in relapsed or refractory AML," stated Philip A. Serlin, Chief Executive Officer of BioLineRx. "In addition, exciting new findings indicate a clear correlation between patient response and mobilization of AML blasts, thus identifying a potential biomarker for selecting patients likely to respond to BL-8040. These encouraging results strongly support the continued development of BL-8040 in relapsed or refractory AML, giving BioLineRx broad therapeutic coverage in the AML space, with potential activity at different stages of the disease and in different patient populations. We look forward to providing additional updates on overall survival from this study, and continue to execute on our other two important AML trials currently ongoing – a large, randomized, controlled Phase 2b study in consolidation AML, and a Phase 1b/2 study in maintenance of AML under our collaboration with Genentech," added Mr. Serlin.

The Phase 2a study consisted of 42 patients in two cohorts: (i) dose-escalation (range 0.5-2.0 mg/kg) and (ii) dose-expansion at the selected dose of 1.5 mg/kg. Patients with r/r AML were treated daily with BL-8040 monotherapy for two days followed by combined administration of BL-8040 and HiDAC for 5 days, for 1-2 cycles. Efficacy endpoints included response rate (CR/CRi), overall survival, duration of response and event-free survival.

BL-8040 in combination with HiDAC was safe and well tolerated at all BL-8040 dose levels (range 0.5-2.0 mg/kg). The response rate for all dosing levels was 29% and median overall survival was 9.1 months, compared with historical data on overall survival of 6.1 months for HiDAC alone. In patients receiving the 1.5 mg/kg dose selected for expansion (n=23), the response rate was 39% and median overall survival was 10.7 months with 1-year, 2-year and 3-year survival rates of 38.1%, 23.8% and 23.8%, respectively. Furthermore, median overall survival for responding patients at the 1.5 mg/kg dose (n=9) was 21.8 months, with 1-year, 2-year and 3-year survival rates of 66.7%, 44.4% and 44.4%, respectively. Responding patients also demonstrated a statistically significant mean 6.3-fold increase (p=0.003) in the number of AML blasts in the peripheral blood following BL-8040 monotherapy treatment, whereas in non-responding patients the mean-fold increase was minor and non-significant (1.66-fold; p=0.21).

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells and immune-cells from the bone marrow, thereby sensitizing cancer cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust mobilization of other cell types, including the mobilization of hematopoietic stem and progenitor cells, T, B, NK and antigen presenting cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

Empliciti (elotuzumab) Plus Pomalidomide and Low-Dose Dexamethasone Reduces the Risk of Disease Progression by 46% Versus Pomalidomide/Dexamethasone Alone in Patients with Relapsed or Refractory Multiple Myeloma

On June 17, 2018 Bristol-Myers Squibb Company (NYSE:BMY) reported that the ELOQUENT-3 trial, an international Phase 2 study evaluating the addition of Empliciti (elotuzumab) to pomalidomide and low-dose dexamethasone (EPd) in patients with relapsed/refractory multiple myeloma (RRMM), achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with EPd compared with pomalidomide and dexamethasone (Pd) alone (Press release, Bristol-Myers Squibb, JUN 17, 2018, View Source [SID1234527359]). ELOQUENT-3 is the only randomized, active-controlled trial to investigate a pomalidomide-based triplet combination in patients with RRMM who received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI).

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Patients randomized to EPd experienced a 46% reduction in risk of disease progression (HR 0.54; 95% CI: 0.34 to 0.86, p=0.0078) compared with patients randomized to Pd alone, with median PFS, the study’s primary endpoint, of 10.3 months (95% CI: 5.6 to not estimable) compared with 4.7 months (95% CI: 2.8 to 7.2) in Pd patients. The PFS benefit experienced among patients randomized to EPd was consistent among patients who had received two to three prior lines of therapy (HR 0.55; 95% CI: 0.31 to 0.98) and four or more prior lines of therapy (HR 0.51; CI 95%: 0.24 to 1.08). The safety profile for EPd was consistent with prior findings for Empliciti and pomalidomide regimens. The full results will be presented in a late-breaking oral session on Sunday, June 17, at 12:30 CEST during the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden.

"The ELOQUENT-3 trial is the first randomized trial comparing the standard of care, pomalidomide and low dose dexamethasone, with and without the addition of a monoclonal antibody. These data support the hypothesis that the addition of elotuzumab to pomalidomide and dexamethasone elicits a synergistic effect and prolongs, significantly, the progression-free survival of heavily pretreated patients with myeloma, regardless of the number of prior therapies," said Meletios A. Dimopoulos, M.D., professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine. "We believe that EPd, if approved by regulatory authorities, could become an important potential treatment option for patients with relapsed/refractory multiple myeloma whose disease has progressed after treatment with lenalidomide and a proteasome inhibitor."

Twice as many patients randomized to EPd responded to therapy compared to patients randomized to Pd alone. Patients randomized to EPd demonstrated an overall response rate (ORR) of 53% (95% CI: 40 to 66), compared with 26% (95% CI: 16 to 40) among patients randomized to Pd. Time to first response was comparable for patients receiving EPd and Pd at 1.95 and 1.91 months, respectively. Median duration of response had not been reached among patients randomized to EPd at time of analysis. Overall survival, a secondary endpoint, although not mature at this time, showed a positive trend favoring EPd over Pd alone (HR 0.62; 95% CI: 0.30 to 1.28).

"Based on survival data we’ve seen to date in relapsed or refractory multiple myeloma, Empliciti in combination with lenalidomide and dexamethasone has been established as an important treatment option for patients," said Jeffrey Jackson, Ph.D., hematology development lead, Bristol-Myers Squibb. "These new data evaluating the EPd combination build on our commitment to understanding the full potential of Empliciti when used in different combinations. We look forward to discussing these data with health authorities."

Treatment-related Grade 3-4 adverse events (AEs) were comparable between EPd and Pd groups. Any-grade infections occurred in 65% of patients in both arms. Rates of the most commonly occurring Grade 3-4 hematologic AEs, neutropenia and anemia, were lower among patients receiving EPd (13% and 10%, respectively) than patients receiving Pd (27% and 20%), despite longer exposure within the EPd arm and similar dose intensity of pomalidomide between arms. AEs led to discontinuation in 18% of patients in the EPd arm, compared with 24% of patients in the Pd arm.

About ELOQUENT-3

The Phase 2 ELOQUENT-3 trial randomized 117 patients with RRMM who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a PI. Patients were randomized 1:1 to receive either EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity. Patients in both the EPd and Pd arms received 4 mg of pomalidomide for days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤75 years or >75 years, respectively. In the EPd arm, elotuzumab was administered at the dose of 10 mg/kg IV weekly for the first 2 cycles and 20 mg/kg monthly starting from cycle 3.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational medicines, including Immuno-Oncology (I-O) therapeutic approaches, for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the integrated scientific understanding of both tumor cell and immune system pathways, through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 24 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance the I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how a patient’s tumor biology can be used as a guide for treatment decisions throughout their journey.

We understand making the promise of transformational medicines like I-O therapies a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Empliciti

Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.

Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

U.S. FDA-APPROVED INDICATION FOR EMPLICITI

EMPLICITI (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

EMPLICITI can cause infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.
Infections

In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly.
Second Primary Malignancies

In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs.
Hepatotoxicity

Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.
Interference with Determination of Complete Response

EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential

There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.
There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.
Adverse Reactions

Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients.
Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).
Please see the full Prescribing Information for EMPLICITI.

Aura Biosciences Announces Update of Clinical Safety and Efficacy Data on Lead Candidate AU-011 for Choroidal Melanoma

On June 17, 2018 Aura Biosciences, a biotechnology company developing a new class of therapies to target and selectively destroy cancer cells using viral capsid conjugates, reported new interim safety and efficacy data from an open-label Phase 1b/2 study of its lead program, light-activated AU-011 for the treatment of primary choroidal melanoma (Press release, Aura Biosciences, JUN 17, 2018, View Source [SID1234527354]). The findings were presented by Ivana Kim, M.D., Co-Director of the Ocular Melanoma Center at Massachusetts Eye and Ear, at the 2018 World Ophthalmology Congress in Barcelona.

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AU-011 is an investigational, first-in-class targeted therapy in development for the treatment of primary choroidal melanoma. FDA has already granted Fast Track Designation and orphan drug designation, recognizing that there are no FDA-approved therapies and that the disease is serious and life-threatening.

AU-011 is being evaluated in a Phase 1b/2 open-label, multicenter trial designed to evaluate the safety and efficacy of single and multiple ascending doses in 30 adult subjects with clinically diagnosed small to medium primary choroidal melanoma.

Interim data presented today show that AU-011 has been generally well-tolerated with no related serious adverse events, no severe adverse events and no dose-limiting toxicities observed. Adverse events were manageable with standard of care treatments and had no further clinical sequelae. Pre-treatment visual acuity was maintained in all subjects that have been followed for 6 to 12 months.

Early efficacy results are very promising with two subjects in the first multiple-ascending-dose cohort showing evidence of reduction in tumor height at 3 months. Further evidence of preliminary efficacy has also been demonstrated with subtherapeutic doses in the single-ascending-dose cohorts providing stable disease with vision preservation up to 12 months.

"We are excited by these preliminary findings showing AU-011 provided local tumor control without loss of visual acuity for a majority of subjects dosed to date," said Dr. Kim. "That is an encouraging sign of progress toward developing a new treatment for this cancer that could preserve much more vision than radiotherapy, which is the current standard of care but not FDA approved for this indication."

"These findings indicate that Aura’s novel, targeted, light-activated treatment could hold real promise for patients with choroidal melanoma," said Cadmus Rich, M.D., Chief Medical Officer of Aura. "Our team is looking forward to continuing our Phase 1b/2 study with Dr. Kim and our other collaborators at leading ophthalmology centers across the country."

About choroidal melanoma
Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary ocular tumor and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device against the exterior of the eye over the tumor. This technique can control the melanoma but can also lead to radiation-related cataract, retinopathy, optic nerve damage and loss of vision. The alternative is enucleation, or removal of the eye. Choroidal melanoma metastasizes to the liver in about 40 percent of cases in the long term (source: OMF), and only 15 percent of patients whose melanoma has metastasized survive beyond five years after diagnosis (source: ACS).

About light-activated AU-011
AU-011 is a first-in-class targeted therapy in development for the primary treatment of choroidal melanoma. The therapy consists of patented viral capsid conjugates (VCC) with IR-700DX dye molecules that are activated with an ophthalmic laser. The VCCs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. The IR-700DX dye molecules are produced by LI-COR Biosciences and are licensed exclusively to Aura for treating ocular cancers. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the membranes of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in the ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.