On November 13, 2019 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a Phase 3 clinical-stage biopharmaceutical company dedicated to developing and commercializing etripamil for the treatment of cardiovascular indications, reported financial results for the third quarter ended September 30, 2019 and provided a clinical and corporate update(Press release, Milestone Pharmaceuticals, NOV 13, 2019, View Source [SID1234551155]).

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"Thanks to the hard work of our study team, a dedicated group of clinical sites, and, importantly, the patients participating in our study, NODE-301 continues to exceed our enrollment and PSVT event rate expectations, with topline data now expected in the middle of the first half of 2020," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "In addition, progress continues with efforts to ramp up our recently initiated global safety study, NODE-303, the largest study ever conducted in PSVT."

Mr. Oliveto added, "I am honored to welcome Dr. Richard Pasternak to our Board of Directors. A cardiologist by training, he brings a wealth of cardiovascular drug development experience that incorporates academia, large pharma and small entrepreneurial companies."

NODE-301 Update

Milestone reported that it now expects to report topline data for the NODE-301 trial in the middle of the first half of 2020. The NODE-301 trial is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of etripamil, the Company’s novel short-acting calcium channel blocker, for terminating paroxysmal supraventricular tachycardia (PSVT) episodes in the outpatient setting. The study is designed to treat an enriched population of those PSVT patients who historically experience 20 minutes or longer PSVT episodes or episodes requiring termination in the emergency department. The primary endpoint of the NODE-301 study is time to conversion of PSVT to sinus rhythm after the administration of study drug, as confirmed by a central independent adjudication committee. Secondary study endpoints include relief of symptoms commonly associated with an episode of PSVT such as heart palpitations, chest pain, anxiety, shortness of breath, dizziness, or fainting, and rating of treatment satisfaction questionnaire for medication (TSQM).

As previously announced, after the NODE-301 trial reaches its target number of adjudicated PSVT events, collection of blinded data from randomized patients who have not yet experienced an event will continue. These data will be analyzed separately as a secondary data set, referred to as NODE-301B, and may contribute further to sub-population analyses and pharmacoeconomic assessments.

Recent Updates

· Richard C. Pasternak, M.D. Appointed to Board of Directors. The Company also reported that Richard C. Pasternak, M.D. has been appointed to its Board of Directors. He brings to Milestone over 40 years of clinical, academic, and biopharmaceutical industry experience in the area of cardiology. He will serve as a member of the Company’s compensation committee.

Dr. Pasternak recently retired from Cerenis Therapeutics (now ABIONYX Pharma), a French publicly-traded company focused on developing treatments for cardiovascular diseases, where he served as Chief Executive Officer and Chair of the Board of Directors. He previously served as Vice President, Head of Cardiovascular Clinical Research, and Head of Global Scientific Affairs and Scientific Leadership, at Merck & Co. from 2004 to 2010. Prior to joining Merck, he was the Director of Preventive Cardiology and Cardiac Rehabilitation at Massachusetts General Hospital, and an Associate Professor of Medicine at Harvard Medical School.

Dr. Pasternak is currently a Clinical Professor at the Weill Cornell Medical College, and serves on the Boards of Anthos Therapeutics and Magenta Medical Ltd. He previously served on the Boards of Essentialis Therapeutics and Haptocure Ltd., as well as several nonprofit organizations. He was also previously a senior advisor to Bay City Capital and Bridge Medicines. Dr. Pasternak has authored more than 100 publications and has lectured internationally on cardiovascular disease drug development. He received his B.A. and M.D. from Yale University, and completed his medical and cardiology training at Massachusetts General Hospital.

·Company to Commence Clinical Evaluation of Etripamil in Atrial Fibrillation with Rapid Ventricular Rate (RVR). In 2020, Milestone plans to initiate a proof-of-concept clinical trial of etripamil for the treatment of patients with atrial fibrillation with RVR, another type of supraventricular tachycardia, in which most patients experience episodes of elevated heart rates and for which L-type calcium channel blockers are approved for rate control.

· Enrolled First Patient in NODE-303 Study. In October 2019, Milestone announced enrollment of the first patient in the Company’s Phase 3 open-label, global safety study of etripamil in patients with PSVT. The study will primarily evaluate the safety of etripamil when self-administered without medical supervision during single or multiple PSVT episodes. Important secondary measures include efficacy, patient quality of life and pharmacoeconomic assessments. The study represents the largest study ever conducted in PSVT, assessing up to 1,500 patient episodes from patients who did not participate in NODE-301 or its open-label safety extension study, NODE-302.

Announced Appointment of Amit Hasija as Chief Financial Officer and Executive Vice President of Corporate Development. In September 2019, the Company announced the appointment of Amit Hasija as Chief Financial Officer and Executive Vice President of Corporate Development. Mr. Hasija brings to Milestone two decades of experience in corporate finance and business development within the healthcare industry.

Third Quarter 2019 Financial Results

· As of September 30, 2019, Milestone had cash, cash equivalents, and short-term investments of $136.5 million and 24.5 million shares outstanding.

·Research and development expense for the third quarter of 2019 was $9.5 million compared with $3.9 million for the prior year period. For the nine months ended September

30, 2019, research and development expense was $27.8 million compared with $9.6 million for the prior year period. The increase in 2019 amounts reflects spending on Milestone’s full Phase 3 clinical program evaluating etripamil for the treatment of PSVT.

·General and administrative expenses for the third quarter of 2019 were $2.1 million compared with $0.6 million for the prior year period. For the nine months ended September 30, 2019, general and administrative expense was $4.7 million compared with $1.8 million for the prior year period. During 2019, Milestone increased its managerial headcount and, as a result, the related personnel costs. In addition, Milestone incurred increased spending for consulting fees, recruiting fees and professional fees, including legal and accounting services incurred to support its IPO.

· Commercial expense for the third quarter of 2019 was $2.1 million compared with $1.2 million for the prior year period. For the nine months ended September 30, 2019, commercial expense was $6.4 million compared with $2.3 million for the prior year period. These increases reflect increased commercial headcount and related costs, continued commercial and market research, increases in Milestone’s patient advocacy activities and costs for its medical affairs team focused on key opinion leaders’ engagement and disease awareness.

·For the third quarter of 2019, operating loss was $12.9 million compared to $5.7 million in 2018. For the nine months ended September 30, 2019, Milestone’s operating loss was $37.0 million compared to $13.5 million in the prior year period.

About Etripamil in Paroxysmal Supraventricular Tachycardia

Paroxysmal Supraventricular Tachycardia (PSVT) is a rapid heart rate condition that starts and stops without warning, often experienced by patients with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting and anxiety. Calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions, however, for episodes of PSVT calcium channel blockers are currently administered intravenously under medical supervision, usually in the emergency department. By contrast, etripamil is designed to serve as a self-administered therapy for the rapid termination of episodes of PSVT. With its combination of convenient delivery, rapid onset and short duration of action, etripamil has the potential to shift the current treatment paradigm for PSVT away from the burdensome and costly emergency department settings by treating episodes of PSVT wherever and whenever they occur.

On November 13, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that members of the management team will present at the following investor conferences (Press release, Deciphera Pharmaceuticals, NOV 13, 2019, View Source [SID1234551154]):

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Jefferies 2019 London Healthcare Conference on Wednesday, November 20 at 2:40 PM GMT in London
Piper Jaffray 31st Annual Healthcare Conference on Thursday, December 5 at 9:30 AM ET in New York
A live webcast of both events will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days following the presentation.

On November 13, 2019 ArQule, Inc. (Nasdaq: ARQL) reported that Paolo Pucci, Chief Executive Officer, will participate in the Jefferies London Healthcare Conference on Wednesday, November 20, 2019 in London, UK (Press release, ArQule, NOV 13, 2019, View Source [SID1234551153]).

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On November 13, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the Italian Medicines Agency (AIFA) has approved rucaparib for reimbursement in Italy (Press release, Clovis Oncology, NOV 13, 2019, View Source [SID1234551135]). Rucaparib will soon be available as an option for monotherapy maintenance treatment for adults with relapsed, platinum-sensitive high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer that has responded to platinum-based chemotherapy.3

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Rucaparib is indicated for eligible patients regardless of BRCA status, which means it can be prescribed for women who harbor a BRCA mutation or who are BRCA wild-type.3

"We very much welcome the arrival of the PARP inhibitor rucaparib, which offers a new treatment option after surgery and two lines of chemotherapy to all eligible women affected by relapsed ovarian cancer," declared Nicoletta Cerana, National President of Acto Onlus, the number one Italian network of patient associations involved in the fight against ovarian cancer and gynecological tumors. "Ovarian cancer is a highly lethal neoplasm which now, thanks to the PARP inhibitors, can finally be made chronic. Patients know this and are ready to embark upon the difficult journey towards chronicity. As an association, we therefore hope that rucaparib can be prescribed as soon as possible in all Italian regions."

Approximately 5,000 women are diagnosed with ovarian cancer in Italy every year, which equates to roughly 14 every day, and accounts for about 30 percent of all malignant tumors of the female reproductive system.4,5 In addition, approximately 25 percent of patients harbor a BRCA1/2 mutation correlating to responsiveness to therapy, while the majority of women who are diagnosed are BRCA wild-type will have a worse prognosis and limited therapeutic options.5,6,7 Despite advancements in treatment and care, more than 3,000 women still die each year.4 The 5-year survival rate for ovarian cancer in Italy is only 39 percent, falling to 31 percent at 10 years.5 Of those treated with surgery and first line chemotherapy, approximately 70 percent of patients will relapse within the first three years.8

"On a personal level, I am very pleased to be able to offer rucaparib to Italian patients as well, as this represents an important innovation," said Nicoletta Colombo, Director of the Oncological Gynecology Program of the European Institute of Oncology in Milan and Associate Professor at the University of Milano-Bicocca. "In the ARIEL3 study, in fact, rucaparib doubled disease-free time after a second line of chemotherapy compared to placebo and with a manageable tolerability profile despite a study population very similar to clinical practice, regardless of the BRCA mutation."

The European Union (EU) authorization is based on data from the pivotal phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved PFS in all ovarian cancer patient populations studied.1 ARIEL3 successfully achieved its primary endpoint of extending investigator-assessed PFS versus placebo in all patients treated (intention-to-treat, or ITT), population, regardless of BRCA status (median 10.8 months vs 5.4 months).1,2 In addition, it successfully achieved the key secondary endpoint of extending PFS by independent radiological review versus placebo in all patients treated (ITT), regardless of BRCA status (median 13.7 months vs 5.4 months).2 The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials.2

"In ovarian cancer, around 80 percent of cases involve women without a BRCA mutation and are characterized by a particularly poor prognosis," explains Professor Sandro Pignata, Director of Medical Oncology of the Urogynecology Department at the National Oncological Institute Pascale Foundation cancer center in Naples, Scientific Coordinator of the Campania Region Oncology Network and President of the MITO Research Group. "The fact that rucaparib is a reimbursable drug makes it an important new treatment option, even for these patients who still too often do not receive safe and effective maintenance therapy."

"The reimbursement of Rubraca in Italy is an important step in the ovarian cancer treatment pathway, as it has shown to be effective across a broad population of women with relapsed ovarian cancer," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are working to make Rubraca available to as many eligible patients as possible across Europe, and we look forward to additional country launches in the coming months."

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 that is being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancer (mCRPC), as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

On November 13, 2019 Alexion Pharmaceuticals (Nasdaq:ALXN) reported that management will present at the 2019 Stifel Healthcare Conference in New York, NY on Tuesday, November 19th, 2019 at 8:35 a.m. ET (Press release, Alexion, NOV 13, 2019, View Source [SID1234551151]).

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An audio webcast of the presentation will be available live. You can access the webcast at: View Source An archived version of the remarks will also be available through the Company’s website for a limited time following the conference.