On March 13, 2020 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) reported an update from the Phase III JAVELIN Head and Neck 100 study evaluating avelumab in addition to chemoradiotherapy (CRT) versus standard-of-care CRT in patients with untreated locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) (Press release, EMD Serono, MAR 13, 2020, View Source [SID1234555553]). The alliance has accepted the recommendation of the independent Data Monitoring Committee (DMC) to terminate the JAVELIN Head and Neck 100 trial, as the study is unlikely to show a statistically significant improvement in the primary endpoint of progression-free survival (PFS) based on a preplanned interim analysis. A detailed analysis of the Phase III JAVELIN Head and Neck 100 study is being conducted and study findings will be shared with the scientific community.

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EMD Serono and Pfizer Logo (PRNewsfoto/EMD Serono)

There has been limited innovation for patients with locally advanced SCCHN over the past 10 years.1 Despite aggressive standard-of-care treatment with high-dose chemotherapy combined with radiotherapy, LA SCCHN will ultimately recur in a large proportion of patients.2 In recognition of the unmet need for additional treatment options that can prevent recurrence or metastatic disease,3 the alliance initiated the JAVELIN Head and Neck 100 trial, which is the first Phase III study to report topline results for an immune checkpoint inhibitor in combination with CRT in LA SCCHN.

About JAVELIN Head and Neck 100
JAVELIN Head and Neck 100 (NCT02952586) is a Phase III, randomized, double-blind, placebo-controlled, parallel-arm study investigating treatment with avelumab plus standard-of-care CRT followed by avelumab maintenance versus CRT alone in patients with previously untreated LA SCCHN. A total of 697 patients who had not received prior therapy for locally advanced SCCHN and were eligible for CRT with curative intent were randomly assigned to receive avelumab plus CRT or CRT alone. The primary endpoint was PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included overall survival (OS), time to locoregional failure, time to distant metastatic failure, overall response, duration of response and pathologic complete response.

About Head and Neck Cancer
Head and neck cancer is the sixth most common cancer worldwide.4 In 2016, there were nearly 150,000 newly diagnosed cases in the United States, Japan and Europe.4 Approximately 60% of people are diagnosed with head and neck cancer when their disease has already progressed to the locally advanced stage (Stage III-IVB).5 At this stage, the cancer has spread from its site of origin to local lymph nodes, but not another part of the body.6 Standard of care for these patients includes high-dose chemotherapy combined with radiotherapy.7

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.8-10 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO Important Safety Information from the US FDA-Approved Label
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

On March 13, 2020 Rubius Therapeutics reported that it is minimizing its focus on its rare disease pipeline and taking greater aim at developing treatments for cancer and autoimmune diseases (Press release, Rubius Therapeutics, MAR 13, 2020, View Source [SID1234555552]). Company stock closed down 39% on Thursday to $3.99 per share.

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On Thursday, the company announced a strategic decision to reprioritize its focus on how its RED PLATFORM could be better used for these indications. Cambridge, Mass.-based Rubius’ technology platform is designed to genetically engineer and culture Red Cell Therapeutics that are "selective, potent and off-the-shelf allogeneic cellular therapies for the potential treatment of several diseases across multiple therapeutic areas." In its announcement, Rubius pointed to its lead oncology program, RTX-240, a broad immunostimulatory Red Cell Therapeutic. The company said the U.S. Food and Drug Administration has approved its Investigational New Drug Application and will soon begin dosing patients in a Phase I trial.

RTX-240 is an allogeneic cellular therapy that is engineered to broadly stimulate the adaptive and innate immune systems to generate an antitumor response, according to company data. Rubius said RTX-240 may provide a different approach to treating solid tumors as the asset "expresses 4-1BBL and IL-15TP, a fusion of IL-15 and IL-15 receptor alpha, on the cell surface with the goal of improving antitumor activity and overcoming resistance to immunotherapy" in cancer patients whose disease has become resistant or refractory to immunotherapies, including checkpoint inhibitors.

In addition to RTX-240, Rubius is also eying the filing of an IND for RTX-321, its first artificial antigen-presenting cell for the treatment of HPV-positive cancers. The company anticipates that filing by the end of 2020. Manufacturing for the two oncology assets will be supported at its Rhode Island facility, which Rubius said it now cGMP ready to produce clinical supply for the assets.

In the autoimmune setting, Rubius is focusing on T cell-mediated autoimmune diseases and is pursuing Type 1 diabetes, along with a number of other undisclosed programs. The company expects to provide an update on its preclinical autoimmune pipeline in the future.

Pablo J. Cagnoni, president and chief executive officer of Rubius, said for the past two years, the company has generated exciting oncology preclinical data, which has demonstrated the ability of its Red Cell Therapeutics to "broadly activate the immune system, and induce tumor-specific responses by activating and expanding antigen-specific T cells with our artificial antigen-presenting cells."

"By focusing on the development of our oncology and autoimmune pipeline, we believe we will have the greatest opportunity to bring life-saving therapies to patients, enhance shareholder value and extend our cash runway into 2022," Cagnoni said in a statement. "With our internal cGMP manufacturing established, we are well-positioned to advance this entirely new class of allogeneic cellular medicines."

As a result of its new focus, Rubius is deprioritizing its RTX-134 program for the treatment of phenylketonuria (PKU), as well as its other rare disease programs. The company said there were multiple factors that lead to its decision, including unanticipated delays mostly due to manufacturing challenges with the company’s contract manufacturing organization. Other challenges included the high cost associated with producing chronic, high-dose therapy for enzyme deficiencies and the continued momentum of the company’s oncology pipeline, Rubius said.

The first patient in the Phase Ib PKU trial was dosed in January. The company noted that the patient’s response to the treatment was well-tolerated but any results were "uninterpretable possibly due, in part, to the low dose of cells administered and the sensitivity of the flow cytometry assay used to detect circulating cells." The company has discontinued the trial.

Future capital investments and improvements in manufacturing efficiency, together with enhancements to the RED PLATFORM, may enable Rubius to revisit chronic, high dose-dependent conditions in the future, the company announced.

On March 13, 2020 Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, reported financial results for the fourth quarter and full year ended December 31, 2019 (Press release, Applied Therapeutics, MAR 13, 2020, View Source [SID1234555551]).

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"This past year was a transformative time for Applied Therapeutics. In addition to our transition to a public company, we completed two additional financings, and made significant progress in our clinical development programs in Diabetic Cardiomyopathy and Galactosemia – both devastating diseases with no treatment options available," said Shoshana Shendelman, Ph.D., Founder, CEO and Chair of the Board of Applied Therapeutics. "With positive results from our pivotal Phase 2 ACTION-Galactosemia study in hand, we plan to move quickly towards regulatory filing, while preparing for Galactosemia commercial launch and growing our organization. On our Diabetic Cardiomyopathy program, we remain on track to fully enroll our Phase 3 registrational study this year, as we continue to advance this potential blockbuster opportunity. Throughout 2020 we’ll continue to move additional candidates into the clinic, while expanding our pipeline – delivering on our core strategy of applying technological advances to high unmet need indications."

Recent Highlights

·Closed $143.4 Million Underwritten Public Offering. In January 2020, we completed an underwritten public offering of common stock at a price to the public of $45.50 per share, resulting in gross proceeds of approximately $143.4 million.

·Announced Positive Topline Results of Pivotal Phase 2 ACTION-Galactosemia Study. In January 2020, we announced positive topline results from the Pivotal Phase 2 portion of the ACTION-Galactosemia study of AT-007, a central nervous system (CNS) penetrant Aldose Reductase inhibitor (ARI), in adult Galactosemia patients. AT-007 treatment resulted in a statistically significant and robust reduction in plasma galactitol vs placebo in adult Galactosemia patients, and AT-007 was well tolerated, with no drug-related adverse events noted. We plan to utilize recent FDA guidance permitting biomarker-based development in low prevalence, slowly progressing rare metabolic diseases, such as Galactosemia, and expect to file for regulatory approval in the second half of 2020. We plan to present the full data from the ACTION-Galactosemia trial at the Society for Inherited Metabolic Disorders Annual Meeting, being held April 26 – 29 in Austin, Texas.

·Presented Pre-Clinical Data Highlighting AT-001 for Treatment of Diabetic Cardiomyopathy at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRDC). In December 2019, we presented pre-clinical data on AT-001, a novel, potent and selective Aldose Reductase inhibitor (ARI) in Phase 3 clinical development for Diabetic Cardiomyopathy at WCIRDC in Los Angeles, California. The data showed a head to head comparison of AT-001 vs a first-generation ARI and highlights the improvements over these prior ARIs.

· Presented Study Design and Rationale for the ARISE-HF Pivotal Study of AT-001 for Treatment of Diabetic Cardiomyopathy at the 16th Annual Global Cardiovascular Clinical Trialist’s Forum (CVCT). In December 2019, we presented the study design and rationale for our ongoing ARISE-HF study at CVCT in Washington, D.C. ARISE-HF is a Phase 3 pivotal study examining effects of AT-001 on functional capacity (as measured by peak V02) in patients with Diabetic Cardiomyopathy at high risk of progression. We expect to announce topline data from the ARISE-HF trial in 2021.

·Presented Clinical Data Highlighting AT-001 for the Treatment of Diabetic Cardiomyopathy at the American Heart Association (AHA) Scientific Sessions 2019. In November 2019, we presented clinical data on AT-001 at AHA 2019 in Philadelphia, Pennsylvania. The data presented support our clinical rationale for development of AT-001 in Diabetic Cardiomyopathy by showing a reduction in NTproBNP, an important cardiac stress biomarker shown to correlate with long term heart failure outcomes and a strong preliminary indicator of efficacy in this patient population.

Financial Results

·Cash and cash equivalents and short-term investments totaled $38.9 million as of December 31, 2019, compared with $18.8 million at December 31, 2018. This does not include approximately $143.4 million in gross process we received from an underwritten public offering of common stock in January 2020.

·Research and development expenses for the year-ended December 31, 2019 were $32.4 million, compared to $11.5 million for the year ended December 31, 2018. The increase of approximately $20.9 million was primarily related to increased activity on our clinical trials, including an increase in clinical and pre-clinical expenses of $12.4 million and drug manufacturing and formulation expenses of $4.1 million, an increase in personnel expenses of $4.6 million that is allocated to research and development, offset by a decrease in regulatory and other expenses of $0.2 million.

·General and administrative expenses were $13.2 million for the year ended December 31, 2019, compared to $2.0 million for the year ended December 31, 2018. The increase of approximately $11.2 million was primarily related to the increase of personnel expenses of $4.4 million due to the portion of the chief executive officer’s salary that is allocated to general and administrative and the hiring of other personnel, including the chief financial officer, and an increase in professional and legal fees of $3.5 million due to the closing of multiple financings and increased IP work, and an increase in other expenses of $3.2 million, primarily due to recruiting efforts for the chief medical officer and rent.

·Net loss for year ended December 31, 2019 was $45.5 million, or $3.55 per basic and diluted common share, compared to a net loss of $16.5 million, or $3.01 per basic and diluted common share, for the year ended December 31, 2018.

On March 13, 2020 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported financial results and business highlights for the fourth quarter ended December 31, 2019 (Press release, Stemline Therapeutics, MAR 13, 2020, View Source [SID1234555550]).

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Robert Francomano, Chief Commercial Officer of Stemline, stated, "Overall, we are very pleased with the solid demand we generated for ELZONRIS in the first year of launch and look to expand our reach in the market as we continue to build a strong commercial foundation. Importantly, new medical claims data align with our independent analyses which support our market size estimates of the BPDCN U.S. patient population. We believe there is significant growth potential ahead and are poised to capture greater market penetration. Based on market assessments, we have already started to implement a new host of tactics to better situate ELZONRIS in this dynamic and emerging market – all of which should benefit growth later this year."

Ivan Bergstein, CEO of Stemline, commented, "Our first year of launch has created a strong foundation for the future growth of the company. We are investing in multiple label expansion opportunities for ELZONRIS in such indications as CMML, MF, and AML, as well as advancing our other pipeline products including felezonexor, our XPO1 inhibitor and SL-1001, our RET kinase inhibitor, toward key inflection points over the coming year and beyond."

Fourth Quarter 2019 Financial Results Review
Net product revenue for ELZONRIS was $11.8 million for the quarter ended December 31, 2019. Stemline began commercial sales of ELZONRIS within the United States in January 2019.

Stemline ended the fourth quarter with $164.4 million in cash, cash equivalents and short-term investments. For the fourth quarter, Stemline reported a net loss of $17.7 million, with net cash expenditures of $10.1 million.

Research and development expenses were $10.5 million for the fourth quarter of 2019, which reflects decrease of $1.6 million compared with $12.1 million for the fourth quarter of 2018. The lower expenses are primarily attributable to higher costs incurred during 4Q18 related to the ELZONRIS BLA filing and manufacturing of ELZONRIS prior to FDA approval.

Selling, general and administrative expenses were $16.5 million for the fourth quarter of 2019, which reflects an increase of $1.6 million compared with $14.9 million for the fourth quarter of 2018. The increase in costs were primarily attributable to ongoing U.S. launch expenses for ELZONRIS and pre-launch ELZONRIS-related costs in support of a potential regulatory approval and launch in the EU.

Corporate Highlights and Key Commercial and Clinical Milestones

BPDCN

·$43.2 million in net revenues for ELZONRIS in 2019

·IQVIA medical claims data identified approximately 534 unique patients in the U.S. in 2018 with at least one claim of Blastic NK-Cell Lymphoma, a former name of BPDCN

·Marketing Authorization Application (MAA) under review by European Medicines Agency (EMA) for potential approval in the EU

·Phase 1/2 trial of ELZONRIS in patients with BPDCN in the maintenance setting, post-stem cell transplant (SCT), open for enrollment

Chronic Myelomonocytic Leukemia (CMML)

·The CMML expansion cohort, Stage 3a, is open for enrollment of two patient populations: relapsed/refractory patients, and first-line, poor prognosis patients not expected to benefit from first line cytoreductive treatment

·Results from Stage 3a are expected to inform the design of the subsequent Stage 3b confirmatory cohort for potential registration

·We expect to provide updates from this trial in ~4Q20/1Q21

Myelofibrosis (MF)

·At ASH (Free ASH Whitepaper) 2019, ELZONRIS data in patients with relapsed/refractory MF was the subject of an oral presentation.

·In the MF clinical trial, ELZONRIS demonstrated efficacy (spleen size reductions and total symptom score [TSS] reductions) with a predictable and manageable safety profile, including in patients with poor prognostic factors, such as thrombocytopenia, CMML-type features/monocytosis, and clonal evolution

·The MF cohort of the ongoing trial has been expanded to include 20-25 additional patients

·We are evaluating relapsed/refractory patients and specific subsets of patients, including patients with monocytosis, thrombocytopenia, and CD123 positivity.

·We expect to provide updates from this trial in ~4Q20/1Q21

Acute Myeloid Leukemia (AML)

·A Phase 1/2 trial of ELZONRIS in combination with other agents in patients with relapsed/refractory AML, treatment-naive AML unfit for chemotherapy, and high-risk myelodysplastic syndrome (MDS) is currently enrolling patients. CD123 expression levels are also being evaluated. We expect to provide updates later this year.

Conference Call Information

The company will host a conference call and webcast on Monday, March 16, 2020 at 8:00 a.m. ET. The conference call can be accessed by dialing 1-800-367-2403 (domestic) or 1-334-777-6978 (international) and referring to conference ID 7728185.

The webcast can be accessed via the company’s website (www.stemline.com), at the bottom of the "Investors & Media" section in the "News & Events" page, and will be available live and for replay shortly after the event.

About ELZONRISÒ

ELZONRISÒ (tagraxofusp), a targeted therapy directed to CD123, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA).

ELZONRIS is also being evaluated in additional clinical trials in other CD123+ indications, including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and others are planned, including a CD123+ all-comers trial.

About BPDCN

BPDCN, formerly blastic NK-cell lymphoma, is an aggressive hematologic malignancy, often with cutaneous manifestations, with historically poor outcomes. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. The World Health Organization (WHO) termed this disease "BPDCN" in 2008; previous names included blastic NK cell lymphoma and agranular CD4+/CD56+ hematodermic neoplasm. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123

CD123 is a cell surface target expressed on a wide range of malignancies including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123+ cells have been detected in the tumor microenvironment of several solid tumors as well as in certain autoimmune disorders including cutaneous lupus and scleroderma.

On March 13, 2020, Aclaris Therapeutics, Inc. (the "Company") reported tha it has entered into an Open Market Sale Agreement (the "Agreement") with Jefferies LLC ("Jefferies") under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.00001 per share (the "Common Stock"), having an aggregate offering price of up to $25,000,000 through Jefferies as its sales agent (Filing, 8-K, Aclaris Therapeutics, MAR 13, 2020, View Source [SID1234555548]). The issuance and sale, if any, of Common Stock by the Company under the Agreement is subject to the effectiveness of the Company’s registration statement on Form S-3, to be filed with the Securities and Exchange Commission on March 13, 2020. The Company makes no assurances as to if or whether the registration statement will become effective or, if it does become effective, as to the continued effectiveness of the registration statement.

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Jefferies may sell the Common Stock by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended. Jefferies will use commercially reasonable efforts to sell the Common Stock from time to time, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay Jefferies a commission equal to three percent (3.0%) of the gross sales proceeds of any Common Stock sold through Jefferies under the Agreement. The Company has provided customary representations, warranties and covenants and the parties have agreed to customary indemnification rights.

The Company is not obligated to make any sales of Common Stock under the Agreement. The offering of shares of Common Stock pursuant to the Agreement will terminate upon the earlier of (i) the sale of all Common Stock subject to the Agreement or (ii) termination of the Agreement in accordance with its terms.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed herewith as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.