On May 17, 2021 Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products in Greater China and other parts of Asia, reported that the China National Medical Products Administration (NMPA) has accepted for review its Biologics License Application for sacituzumab govitecan-hziy (SG), an investigational therapy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Everest Medicines, MAY 17, 2021, View Source [SID1234580175]).

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"This aggressive and difficult-to-treat disease has historically had very limited treatment options, with overall survival remaining unchanged among patients for nearly two decades," said Yang Shi, Chief Medical Officer for Oncology at Everest Medicines. "The outstanding and robust efficacy and safety results from the global Phase 3 ASCENT study demonstrate SG is an important potential new treatment option for people in China with metastatic TNBC."

"We are excited to achieve this important milestone as we work to advance access to this first-of-its-kind therapy for patients with metastatic TNBC in China and the Asia Pacific region. The speed at which this milestone is achieved is a testament to our steadfast commitment to accelerating global pharmaceutical innovation in diseases with critical unmet needs," said Kerry Blanchard, MD, PhD, CEO of Everest Medicines.

Under the trade name Trodelvy, the U.S. Food and Drug Administration previously granted accelerated approval to SG in April 2020 and full approval in April 2021 for adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.

The Ministry of Food and Drug Safety in South Korea has also recently granted Fast Track Designation and Orphan Drug Designation to SG for the treatment of metastatic TNBC. In addition, Everest announced in January 2021 that it submitted a New Drug Application to the Health Sciences Authority of Singapore for SG for the treatment of patients with metastatic TNBC who have received at least two prior therapies for metastatic disease. That application is currently under review.

About Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly aggressive disease and accounts for approximately 15% of all breast cancer types worldwide. The median age of breast cancer diagnoses tends to be younger in Asian than western countries, and the percentage of the TNBC molecular subtype has been increasing in the past 10 years. TNBC cells lack sufficient estrogen, progesterone or HER2 receptor expression to benefit from the use of hormonal or HER2-directed therapy. Overall survival among patients with this form of breast cancer has not changed in the past 20 years, which highlights the need for advances in therapeutic options for these patients.

About Sacituzumab Govitecan-hziy

Sacituzumab govitecan-hziy (SG) is a first-in-class antibody and topoisomerase inhibitor conjugate directed at TROP-2, a protein frequently expressed in multiple types of epithelial cancers. SG is approved in the United States under the trade name Trodelvy. The U.S. approval was supported by data from the Phase 3 ASCENT study, which demonstrated a statistically significant and clinically meaningful 57% reduction in the risk of disease worsening or death (progression-free survival or PFS), extending median PFS to 4.8 months from 1.7 months with chemotherapy (HR: 0.43; 95% CI: 0.35-0.54; p<0.0001). SG also extended median overall survival (OS) to 11.8 months vs. 6.9 months (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001), representing a 49% reduction in the risk of death.

The most frequent Grade ≥3 adverse reactions for SG compared to single-agent chemotherapy in the study were neutropenia (52% vs. 34%), diarrhea (11% vs. 1%), leukopenia (11% vs. 6%) and anemia (9% vs. 6%). Adverse reactions leading to treatment discontinuation occurred in 5% of patients receiving SG. The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea.

Under a licensing agreement with Gilead Sciences, Inc., Everest Medicines has exclusive rights to develop, register, and commercialize SG for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries. In October 2020, SG was included in the updated 2020 China Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer, compiled by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Cancer Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association.

On May 17, 2021 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines,reported financial results for the first quarter ended March 31, 2021 and provided a clinical, regulatory, and corporate update (Press release, Milestone Pharmaceuticals, MAY 17, 2021, View Source [SID1234580174]).

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"We continue to work closely with our existing clinical trial sites, as well as add new sites, to address the impact that the COVID-19 pandemic has had on patient enrollment in the pivotal Phase 3 RAPID trial of etripamil in patients with PSVT. While we are encouraged by recent improvements in enrollment rates, we now expect to report topline data from the RAPID trial in the second half of 2022," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "We are also pleased to announce that following FDA’s review of the etripamil program’s interim safety data, including that from the initial repeat dose experience from the RAPID trial, we will be adding the higher exposure, repeat dose regimen into the ongoing NODE-303 open-label safety study. We continue to believe etripamil has the potential to serve as an important new option for patients with PSVT, and we are committed to ensuring it is able to realize its full potential."

Mr. Oliveto added, "Earlier today, we were excited to announce that we have entered into an exclusive license agreement with Ji Xing Pharmaceuticals to develop and, if approved, commercialize the investigational drug etripamil for PSVT in greater China. This agreement strengthens both our balance sheet and our executional capabilities, and we look forward to working with the Ji Xing team to expand the potential reach of etripamil to patients in the greater China region."

Recent Updates

Announced Exclusive License Agreement with Ji Xing Pharmaceuticals to Develop and Commercialize Etripamil for PSVT in Greater China. Milestone reported that it has entered an exclusive license and collaboration agreement with Ji Xing Pharmaceuticals (Ji Xing), a biotechnology company headquartered in Shanghai and backed by RTW Investments, LP (RTW) focused on advancing innovative medicines in China, to develop and, if approved, commercialize the investigational drug etripamil in patients with paroxysmal supraventricular tachycardia (PSVT) and additional cardiovascular conditions in Greater China. Milestone will receive an upfront cash payment consisting of $15 million and a $5 million equity investment by RTW Investments. In addition, Milestone is eligible to receive up to $107.5 million in milestone payments and royalties on future sales of etripamil in Greater China. Milestone will supply etripamil and delivery devices to Ji Xing. Ji Xing will be responsible for development and commercialization costs in Greater China.
Company Expects to Report Topline Data from Pivotal Phase 3 RAPID Trial in 2H22. Enrollment remains ongoing in the pivotal Phase 3 RAPID trial of etripamil nasal spray in patients with PSVT. The ongoing COVID-19 pandemic has restricted access to many medical centers, reduced visits to physician offices, and caused patients to delay medical care. The Company continues to work diligently with investigators to identify potential site-specific solutions to mitigate these COVID-related delays, and has also increased the number of participating centers. Milestone now expects to report topline data in the second half of 2022. The Company believes its current cash resources, including the upfront payment from Ji Xing and proceeds from the equity investment from RTW, will be sufficient to support operations beyond the data readout into mid-2023.
The RAPID trial, which is targeting a total of 180 adjudicated paroxysmal supraventricular tachycardia (PSVT) events, is expected to randomize approximately 500 patients 1:1 to receive either etripamil nasal spray or placebo. As previously announced, to maximize the potential treatment effect of etripamil, patients will be directed to administer a second dose of study drug if they do not experience symptom relief within 10 minutes of the first study drug administration. The primary efficacy analysis for both the RAPID trial and the completed NODE-301 trial will be time to conversion of SVT over the first 30 minutes following initial study drug administration, with a target p-value of less than 0.05 for each trial. The RAPID and NODE-301 trials could potentially serve to fulfill the efficacy requirement for a future New Drug Application (NDA) for etripamil in patients with PSVT.
NODE-303 Open-Label Safety Study Amended to Include Repeat Dose of Etripamil. Following an interim safety data analysis of the RAPID study, the Company requested and the U.S. Food and Drug Administration (FDA) agreed to amend the ongoing NODE-303 study to allow a repeat dose of etripamil if symptoms persist for 10 minutes after the first dose. NODE-303 is a global open-label study which primarily evaluates the safety of etripamil when self-administered without medical supervision during single or multiple SVT episodes. Important secondary measures include efficacy, patient quality of life, and pharmacoeconomic assessments.
Data from NODE-301 Trial Featured During Oral Presentation at the American College of Cardiology 70th Annual Scientific Session and Expo (ACC.21). An oral presentation titled, "Etripamil Nasal Spray Relieves Symptoms And Reduces Emergency Room Interventions In Patients With Paroxysmal Supraventricular Tachycardia (PSVT): Analysis Of Clinical Outcomes In The NODE-301 Trial" (#403-13), was featured at the recent ACC.21 virtual meeting. The presentation was delivered by Bruce Stambler, MD, FHRS, Piedmont Heart Institute, Atlanta, GA, and investigator in the NODE-301 trial.
Enrollment Continues in ReVeRA Phase 2 Proof-of-Concept Trial Evaluating Etripamil in Patients with Atrial Fibrillation and Rapid Ventricular Rate (AFib-RVR). In March 2021, Milestone announced that the first patient was enrolled in ReVeRA, its Phase 2 proof-of-concept study of etripamil nasal spray in patients experiencing AFib-RVR. Patient enrollment is ongoing, with the trial expected to enroll approximately 50 patients randomized 1:1 to receive either 70 mg of etripamil nasal spray or placebo. The Phase 2 double blind, placebo controlled, proof-of-concept study is designed to assess the safety and efficacy of etripamil nasal spray to reduce ventricular rate in patients with AFib-RVR experiencing an episode of elevated heart rate requiring treatment. The trial will be conducted in Canada in collaboration with the Montreal Heart Institute and other research centers. The primary endpoint will assess reduction in ventricular rate, with key secondary endpoints including the time to achieve the maximum reduction in rate and duration of the effect.
First Quarter 2021 Financial Results

As of March 31, 2021, Milestone had cash, cash equivalents, and short-term investments of $129.9 million and 29.8 million common shares and 11.4 million common shares issuable upon exercise of pre-funded warrants outstanding.
Research and development expense for the first quarter of 2021 was $8.6 million compared with $11.9 million for the prior year period. The COVID-19 pandemic contributed to delays in new clinical site initiation and patient enrollment, which translated into lower than expected research and development spending in the quarter ended March 31, 2021.
General and administrative expense for the first quarter of 2021 was $2.6 million compared with $2.7 million for the prior year period.
Commercial expense for the first quarter of 2021 was $1.4 million compared with $2.2 million for the prior year period. The decrease of commercial expense in the quarter ended March 31, 2021 reflects efforts in reducing operating expenses affecting primarily pre-commercialization activities as Milestone focused its efforts on an optimized clinical development pathway for etripamil.
For the first quarter of 2021, operating loss was $12.6 million compared to $16.8 million for the prior year period.
About Paroxysmal Supraventricular Tachycardia

Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start and stop suddenly and without warning which affects approximately two million Americans. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions. However, calcium channel blockers approved for the termination of SVT episodes must be administered intravenously under medical supervision, usually in an emergency department or other acute care setting.

About Atrial Fibrillation and Rapid Ventricular Rate

Atrial fibrillation (AFib) is a common arrhythmia marked by an irregular and often rapid heartbeat. AFib is estimated to affect five million patients in the United States, a prevalence projected by the Centers for Disease Control to increase to twelve million patients within the next 10 years. Atrial fibrillation and rapid ventricular rate (AFib-RVR) is a condition in which patients with AFib experience episodes of abnormally high heart rate, often with symptoms such as palpitations, shortness of breath, dizziness, and weakness. Oral calcium channel blockers and/or beta blockers are commonly used to manage heart rate in this condition. When episodes do occur, the corresponding symptoms often cause patients to seek care in the acute care setting such as the emergency department, where standard of care procedures include intravenous administration of calcium channel blockers or beta blockers under medical supervision. Milestone’s initial qualitative market research indicates approximately 40% of patients with AFib experience one or more symptomatic episodes of AFib-RVR per year that require treatment, suggesting a target addressable market for etripamil in patients with AFib of approximately two million patients.

About Etripamil

Etripamil, Milestone’s lead investigational product, is a novel calcium channel blocker designed to be a rapid-response therapy for episodic cardiovascular conditions. As a nasal spray that is self-administered by the patient, etripamil has the potential to shift the current treatment experience for many patients from the emergency department to the at-home setting. Milestone is conducting a comprehensive development program for etripamil, with Phase 3 trials ongoing in paroxysmal supraventricular tachycardia (PSVT) and now a Phase 2 proof-of-concept trial underway in patients with atrial fibrillation and rapid ventricular rate (AFib-RVR).

On May 17, 2021 Soteria Biotherapeutics, Inc. ("Soteria"), a privately-held, immuno-oncology company focused on developing a next generation of switchable bispecific T-cell engagers to treat patients with solid tumor cancers, reported a $42 million Series A financing led by Roche Venture Fund and 5AM Ventures with participation from other leading investors, including M Ventures, Novartis Venture Fund and Alexandria Venture Investments (Press release, Soteria Biotherapeutics, MAY 17, 2021, View Source [SID1234580173]).

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Soteria’s T-LITETM T-cell engagers are selectively switched on through oral administration of a small-molecule activator to modulate potent T-cell activity by controlling the timing, duration, and level of bispecific complex formation. This switchable activity enables precise on/off control over the timing and magnitude of T-cell redirection and cytotoxic activity. Unlike conventional T-cell engagers which lack a control switch and therefore are associated with significant side effects, Soteria’s T-LITE therapies are being designed to allow physicians to modulate T-cell activity to maximize efficacy while minimizing side effects.

"Soteria’s technology has the potential to revolutionize the T-cell engager field with its proprietary approach designed to control and target potent biologic immune activators to attack tumors," said Nisha Marathe, investment director at Roche Venture Fund. "Specifically, we believe the T-LITE technology is highly differentiated, where the potent activity of a T-cell engager can be selectively switched on by small-molecule activators to direct tumor cytotoxicity and reduce cytokine release syndrome, ultimately resulting in a therapy with potentially greater safety and efficacy."

"These funds will support the advancement of our technology and allow us to build a pipeline of T-LITE development candidates with potential in well validated cancer targets," said Kristine Ball, chief executive officer of Soteria. "We appreciate the confidence and vision this syndicate of premier investors has shown in our opportunity to disrupt the T-cell engager field and our potential to create differentiated, potent therapies against solid tumors."

Company Founders and Leadership
Soteria’s team of founders, management and board members brings together accomplished leaders from academia and the biopharma industry with successful track records discovering and developing therapeutics at companies such as Abgenix, Ascendis Pharma, AstraZeneca/Medimmune, Exelixis, Genentech/Roche, KAI (acquired by Amgen), Labrys (acquired by TEVA), Merck Research Laboratories, Novartis, Relypsa (acquired by Vifor) and Sunesis:

Kristine Ball, Chief Executive Officer and Member of the Board
Zachary Hill, PhD, Co-Founder and SVP, Chief Scientific Officer, and Member of the Board
Mohammad Tabrizi, PhD, VP Preclinical Development
Alex Martinko, PhD, Co-Founder and Senior Director of Protein Science
Jim Wells, PhD, Academic Co-founder, Chair of Scientific Advisory Board, and Professor of Pharmaceutical Chemistry at UC San Francisco
Steven P. James, Board Chair and Chief Executive Officer of Pionyr Immunotherapeutics
David Allison, PhD, Member of the Board and Partner at 5AM Ventures
Keno Gutierrez, PhD, Member of the Board and Vice President at M Ventures
Nisha Marathe, PhD, Member of the Board and Investment Director at Roche Venture Fund
David Morris, MD, Member of the Board and Operating Partner at Novartis Venture Fund
Momo Wu, PhD, Member of the Board and Portfolio Investment Manager at Emerson Collective

On May 17, 2021 AffyImmune Therapeutics, Inc., a clinical stage biotechnology company finding safe, effective ways to use CAR T cells against solid cancers, reported that the US Food and Drug Administration (FDA) granted Fast Track designation to its lead compound, AIC100, for the treatment of anaplastic thyroid cancer and refractory poorly differentiated thyroid cancer (Press release, AffyImmune Therapeutics, MAY 17, 2021, View Source [SID1234580172]). The company previously received Orphan Drug designation for AIC100.

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The FDA’s Fast Track designation is designed to facilitate development and expedite review of drug candidates to treat serious conditions and address an unmet medical need. Receipt of Fast Track designation provides grounds for more frequent interaction with the FDA throughout the drug development process for more rapid advancement, earlier approval and access for patients.

"We are pleased to have received Fast Track designation for our first-in-human CAR T cell product currently being tested in patients with refractory thyroid cancer," remarked Eric von Hofe, President and COO of AffyImmune. "It highlights the unmet need in treating refractory solid tumors and points to the potential of AIC100 to address that need. We look forward to a close relationship with the FDA to expedite development and future approvals."

In connection with the approval, AffyImmune has made available its expanded access policy for AIC100 at View Source

On May 17, 2021 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported its financial results for the first quarter ended March 31, 2021, and provided a business update (Press release, Nuvation Bio, MAY 17, 2021, View Source [SID1234580171]).

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"Nuvation Bio continues to make meaningful progress on advancing our deep pipeline of therapies for difficult-to-treat cancers and remains on track to submit five additional Investigational New Drug (IND) applications by 2026," said David Hung, M.D., founder and chief executive officer of Nuvation Bio. "We also continue to enroll and dose patients in our Phase 1/2 study of NUV-422, our lead cyclin-dependent kinase (CDK) 2/4/6 inhibitor, in high-grade gliomas and expect top-line data from the Phase 1 portion of this study in 2022. Our strong cash, cash equivalents and marketable securities of $824.7 million at the end of the first quarter provides us sufficient resources to continue to execute on our robust clinical development plan and grow our pipeline of novel and mechanistically distinct cancer treatments."

Recent Business Highlights

Enrollment ongoing in Phase 1/2 study of NUV-422. Nuvation Bio continues to enroll and dose patients in the Phase 1/2 study of its lead investigational compound, NUV-422, a CDK 2/4/6 inhibitor, in adult patients with recurrent or refractory high-grade gliomas, including glioblastoma multiforme (GBM). The Phase 1 dose escalation portion of the study is designed to evaluate safety and tolerability, as well as to determine a recommended Phase 2 dose based on the tolerability profile and pharmacokinetic properties of NUV-422. The Phase 2 dose expansion portion of the study is expected to initially focus on patients with high-grade gliomas and is designed to evaluate overall response rate, duration of response and survival. Data from the Phase 1 portion of this study is expected in 2022.
First Quarter 2021 Financial Results

As of March 31, 2021, Nuvation Bio had cash, cash equivalents, and marketable securities of $824.7 million.

For the three months ended March 31, 2021, research and development expenses were $15.9 million, compared to $7.3 million for the three months ended March 31, 2020. The increase of $8.6 million was due to an increase in third-party costs related to research services and manufacturing to advance our current preclinical programs and Phase 1/2 clinical trial. Also, the current period includes approximately $3.7 million related to the issuance of common stock as consideration for the purchase of in-process research and development.

For the three months ended March 31, 2021, general and administrative expenses were $4.6 million, compared to $1.9 million for the three months ended March 31, 2020. The increase of $2.7 million was due to increased personnel-related costs driven by an increase in headcount, as well as increases in professional fees, insurance costs and tax expense.

For the three months ended March 31, 2021, Nuvation Bio reported a net loss of $20.4 million, or $(0.12) per share. This compares to a net loss of $8.7 million, or $(0.10) per share, for the comparable period in 2020.

Restatement of Panacea Financial Statements

Nuvation Bio also announced that, as reported in a Current Report on Form 8-K filed with the SEC on May 14, 2021, as a result of guidance provided by the SEC on April 12, 2021 regarding the accounting for warrants issued by special purpose acquisition companies (SPACs), it is restating the previously issued 2020 consolidated financial statements of Panacea Acquisition Corp. (Panacea). Panacea combined with Nuvation Bio Inc. (Legacy Nuvation Bio) and changed its name to Nuvation Bio Inc. on February 10, 2021 (the Merger).

The restatement pertains to the accounting treatment for Panacea’s public and private placement warrants that were outstanding on December 31, 2020, as well as the forward purchase agreement (the "FPA") with certain anchor investors, which provided for the potential future issuance of securities, including additional warrants. Consistent with market practice among SPACs, Panacea had been accounting for the warrants and the FPA as equity under a fixed accounting model. However, in light of the recent SEC guidance, we are restating Panacea’s historical financial statements for the year ended December 31, 2020 such that the warrants and the FPA are accounted for as liabilities and marked-to-market each reporting period. In general, under the mark-to-market accounting model, we measure the fair value of the liability-classified warrants and the FPA at the end of each reporting period and recognize any changes in their fair value in our operating results. As of December 31, 2020, Panacea had 4,954,167 warrants outstanding and subject to reclassification. Upon completion of the Merger, an additional 833,333 warrants were issued pursuant to the FPA.

The change in accounting treatment does not impact the historical financial statements of Legacy Nuvation Bio, which became the historical financial statements of the combined company upon completion of the Merger. In addition, Nuvation Bio currently expects that the reclassification of the warrants will have no impact on the liquidity or cash or cash equivalents in the historical financial statements of Panacea.