Moleculin Approved to Accelerate European Clinical Trial

On April 28, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates, reported that it is now authorized by the Polish Department of Registration of Medicinal Products known as URPL to accelerate the Phase 1 dose escalation portion of its clinical trial of Annamycin for the treatment of acute myeloid leukemia (AML) (Press release, Moleculin, APR 28, 2020, View Source [SID1234556677]).

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

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

                  Schedule Your 30 min Free Demo!

Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

The URPL has allowed an amendment to the Annamycin clinical trial protocol, which among other things, includes an increase in the dose escalation increment between cohorts from 30 mg/m2 to 60 mg/m2. The clinical trial is currently recruiting for the 240 mg/m2 cohort, so this amendment allows the next cohort to increase to 300 mg/m2, assuming all requirements for safety are met with the 240 mg/m2 cohort.

"Now that we have begun to demonstrate the absence of any cardiotoxicity associated with Annamycin," commented Walter Klemp, Chairman and CEO of Moleculin. "We believe we can and should move more aggressively to establish the maximum tolerated dose, or MTD, for Annamycin. This authorization now sets the stage to accelerate the dose escalation process. Thus far, even though we’ve seen promising activity from Annamycin, our dosing levels are still sub-therapeutic. Based on prior clinical experience with Annamycin, the 300 mg/m2 dosing level will be our first opportunity to test Annamycin at what we expect will be therapeutic levels."

Blueprint Medicines Announces Top-line Results from Phase 3 VOYAGER Trial of
Avapritinib versus Regorafenib in Patients with Advanced Gastrointestinal Stromal Tumor

On April 28, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported top-line results from the Phase 3 VOYAGER clinical trial of avapritinib versus regorafenib in patients with locally advanced unresectable or metastatic gastrointestinal stromal tumor (GIST) (Press release, Blueprint Medicines, APR 28, 2020, View Source [SID1234556676]). The VOYAGER trial did not meet the primary endpoint of an improvement in progression-free survival (PFS) for avapritinib versus regorafenib. Top-line safety data for avapritinib were consistent with those previously reported.

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

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

                  Schedule Your 30 min Free Demo!

Blueprint Medicines plans to continue to commercialize AYVAKIT (avapritinib) in the United States for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations, and seek marketing approval for avapritinib for the treatment of this patient population in additional geographies. Blueprint Medicines continues to anticipate a decision from the European Commission on its marketing authorization application for the treatment of adults with PDGFRA D842V mutant GIST in the third quarter of 2020. Based on the top-line VOYAGER data, the company plans to discontinue further development of avapritinib in GIST beyond PDGFRA exon 18 mutant GIST.

"While we are disappointed by the outcome of the VOYAGER trial, we are deeply grateful to the patients, investigators and clinical site staff who contributed to the completion of this global study. We hope these data will reveal important insights to improve the scientific understanding of the disease and inform future innovations in GIST, and we are committed to sharing the results at a future medical meeting," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "At Blueprint Medicines, we strive to advance science, building on successes and learning from setbacks, to create new medicines for patients with difficult-to-treat cancers and rare diseases. With a deep portfolio of precision therapies and a strong financial position, we will continue to advance our pipeline with clear near-term priorities in systemic mastocytosis and RET-altered cancers."

Top-line Data from Phase 3 VOYAGER Trial

The VOYAGER trial evaluated the efficacy and safety of avapritinib (N=240) versus regorafenib (N=236) in patients with third- or fourth-line GIST.

Avapritinib showed a median PFS of 4.2 months compared to 5.6 months for regorafenib. The difference in median PFS between the avapritinib and regorafenib groups was not statistically significant. The overall response rate was 17 percent for the avapritinib group and 7 percent for the regorafenib group.

Avapritinib was generally well-tolerated with most adverse events reported as Grade 1 or 2. Top-line safety results were consistent with previously reported data, and no new safety signals were observed.

Additional analyses of the VOYAGER trial results are ongoing, and Blueprint Medicines plans to present the data at a future medical meeting.

Financial Guidance

Based on its current operating plans, Blueprint Medicines continues to expect that its existing cash, cash equivalents and investments together with anticipated product revenues but excluding any additional potential option fees, milestone payments or other payments under its collaboration or license agreements, will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the second half of 2022. Anticipated savings from the discontinuation of further development of avapritinib in non-PDGFRA exon 18 mutant GIST indications is expected to offset any previously forecast revenues from those indications through 2022.

As of December 31, 2019, Blueprint Medicines had cash, cash equivalents and investments of $548.0 million. In addition, Blueprint Medicines received $308.4 million in estimated net proceeds from its January 2020 follow-on public offering.

Conference Call Information

Blueprint Medicines will host a live webcast today beginning at 8:00 a.m. ET to discuss the top-line data from the VOYAGER trial. To access the live call, please dial (855) 728-4793 (domestic) or (503) 343-6666 (international), and refer to conference ID 2207088. A webcast of the conference call will be available in the Investors & Media section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.

About the VOYAGER Trial

VOYAGER was a global, open-label, randomized, Phase 3 trial designed to evaluate the efficacy and safety of avapritinib versus regorafenib in patients with third- or fourth-line GIST. Patients were randomized 1:1 to receive either avapritinib (300 mg once daily dosing) or regorafenib (160 mg once daily dosing for three out of every four weeks) at multiple sites in the United States, Canada, European Union, Australia and Asia. The primary efficacy endpoint was PFS by blinded, independent central radiology review, based on modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST 1.1 criteria) for GIST. For more information about the VOYAGER trial, please visit www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03465722).

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. AYVAKIT is the first precision therapy approved to treat a genomically defined population of patients with GIST and the only highly active treatment for PDGFRA exon 18 mutant GIST. The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation. For more information, visit AYVAKIT.com.

Avapritinib is not approved for the treatment of any other indication in the U.S. or any other jurisdiction by the FDA or any other health authority.

Blueprint Medicines is developing avapritinib globally for the treatment of advanced, smoldering and indolent systemic mastocytosis (SM). The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, HongKong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

Affimed Reports 2019 Financial Results and Recent Operational Progress

On April 28, 2019 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company committed to giving patients back their innate ability to fight cancer, reported financial results for the year ended December 31, 2019 and provided an update on clinical and corporate progress (Press release, Affimed, APR 28, 2020, View Source [SID1234556675]).

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

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

                  Schedule Your 30 min Free Demo!

"Our clinical trials currently remain active, and we are working closely with our participating physicians and clinical sites to minimize the impact on further progress as they focus on addressing the evolving COVID-19 global health crisis," said Dr. Adi Hoess, Affimed’s CEO. "During these unprecedented and challenging times, our top priority continues to be supporting our employees, patients and our healthcare partners, while ensuring the continuity of our operations."

Development Program Updates

Affimed remains committed to continuing its development programs but acknowledges the impact from the evolving COVID-19 pandemic on clinical studies, including potential delays in patient enrollment. The company plans to update expected timing of milestones for its clinical studies after there is more clarity on the duration and magnitude of the impact from the COVID-19 pandemic.

AFM13 (CD30/CD16A)

Patient enrollment is ongoing in the Phase 2 registration-directed study of AFM13 as a monotherapy in relapsed or refractory patients with CD30-positive peripheral T cell lymphoma (pTCL). Affimed has successfully activated 42 clinical study sites across nine countries. To ensure patient safety and to avoid imposing additional burdens on healthcare systems already strained by the COVID-19 pandemic, the company has taken the decision to temporarily pause enrollment in the exploratory cohort of patients with CD30-positive relapsed or refractory transformed mycosis fungoides.

In March 2020, enrollment of all 15 patients was completed in an investigator-sponsored Phase 1b/2a study of AFM13 in patients with relapsed or refractory CD30-positive lymphoma with cutaneous manifestation led by Columbia University. Previously reported data from the study confirmed single-agent activity of AFM13, with an objective response rate (ORR) of 50% (5 of 10 patients).

Affimed is in close collaboration with the University of Texas MD Anderson Cancer Center (MDACC) to initiate an investigator-sponsored Phase 1 study to investigate the combination of AFM13 with allogeneic NK cells. MDACC intends to administer a stable complex of AFM13 pre-mixed with cord blood-derived allogeneic NK cells in different doses (numbers of pre-loaded NK cells) to patients with relapsed/refractory CD30-positive lymphoid malignancies.

AFM24 (EGFR/CD16A)

The first patient was successfully dosed in a first-in-human Phase 1/2a clinical trial of AFM24. The study is an open-label, non-randomized, multi-center, multiple ascending dose escalation/expansion study to evaluate AFM24 as monotherapy in patients with advanced solid malignancies known to be EGFR-positive and whose disease has progressed after treatment with previous anticancer therapies.

Preclinical Pipeline Update

Affimed continues to progress AFM28 and AFM32 as preclinical research currently remains unimpacted by the COVID-19 pandemic.

Genentech Collaboration Update

In November 2019, Genentech exercised its final option for an exclusive target under the ongoing, multi-program strategic oncology collaboration agreement to develop and commercialize novel NK cell engager-based immunotherapeutics generated from Affimed’s ROCK platform to treat multiple cancers. Affimed received a payment from Genentech in an undisclosed amount based on this achievement. Affimed and Genentech

continue to progress multiple programs under the ongoing strategic, multi-target collaboration.

Management Appointments

Dr. Andreas Harstrick joined Affimed as Chief Medical Officer (CMO) in March 2020 and Dr. Arndt Schottelius joined the company as Chief Scientific Officer (CSO) in April 2020. Dr. Harstrick brings a track record of running successful clinical trials that have led to regulatory approvals, deep oncology expertise, and a proven ability to lead large clinical organizations. Dr. Schottelius brings extensive innate immunity expertise, R&D leadership and a successful record of advancing and translating discovery research into preclinical and clinical development.

COVID-19 Impact Mitigation

COVID-19 has significantly impacted the global healthcare system, including the conduct of clinical trials as medical institutions prioritize the treatment of those afflicted with COVID-19. Affimed has taken several important actions to balance the commitment to treat cancer patients and to mitigate potential health and safety risks posed by the COVID-19 pandemic, while maintaining continuity of its operations and preserving financial flexibility for the future.

Full Year 2019 Financial Highlights

Cash, cash equivalents and current financial assets totaled €104.1 million as of December 31, 2019 compared to €108.8 million as of December 31, 2018. During the fourth quarter of 2019, the company raised €29.5 million in net proceeds, after deducting underwriting discounts and commissions and estimated offering expenses, from a completed public offering. Based on its current operating plan and assumptions, Affimed anticipates that its cash, cash equivalents and current financial assets as of December 31, 2019 will support operations at least into the first half of 2022.

Net cash used in operating activities was €29.1 million for the twelve months ended December 31, 2019, compared to net cash from operating activities of €49.4 million for the twelve months ended December 31, 2018. The net cash from operating activities in 2018 includes an initial upfront payment and committed funding of €83.2 million ($96.0 million) from the strategic collaboration Affimed entered into with Genentech Inc. in August 2018.

Total revenue was €21.4 million for the year ended December 31, 2019 compared to €23.7 million for the year ended December 31, 2018. Revenue in both years is attributable primarily to the recognition of revenue from the Genentech collaboration in the respective years.

Research and development (R&D) expenses were €43.8 million for the year ended December 31, 2019, compared to €35.1 million for the year ended December 31, 2018. The increase was primarily related to higher expenses for startup activities for the AFM13 registration-directed study in pTCL, manufacturing activities for AFM13 clinical study material, and early stage development and discovery activities.

General and administrative (G&A) expenses were €10.3 million for the year ended December 31, 2019, compared to €9.6 million for the year ended December 31, 2018. In 2019, G&A expenses were primarily related to personnel expenses and legal, consulting and audit costs.

Net loss was €32.4 million, or €0.50 per common share, for the year ended December 31, 2019, compared to a net loss of €19.5 million, or €0.32 per common share, for the year ended December 31, 2018.

Additional information regarding these results is included in the notes to the consolidated financial statements as of December 31, 2019 and "Item 5. Operating and Financial Review and Prospects," which will be included in Affimed’s Annual Report on Form 20-F as filed with the U.S. Securities and Exchange Commission (SEC).

Note on International Financial Reporting Standards (IFRS)

Affimed prepares and reports the consolidated financial statements and financial information in accordance with IFRS as issued by the International Accounting Standards Board. None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles in the United States. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information

Affimed will host a conference call and webcast today, Tuesday, April 28, 2020 at 8:30 a.m. Eastern time to discuss the company’s 2019 financial results and recent corporate developments. The conference call will be available via phone and webcast. To access the call, please dial +1 (877) 870-9135 for U.S. callers, or +44 (0) 2071 928338 for international callers, and reference passcode 7978047 approximately 15 minutes prior to the call.

A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source, and a replay of the webcast will be accessible at the same link for 30 days following the call.

Merck Announces First-Quarter 2020 Financial Results

On April 28, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported financial results for the first quarter of 2020 (Press release, Merck & Co, APR 28, 2020, View Source [SID1234556674]).

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

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

                  Schedule Your 30 min Free Demo!

"In this challenging and unprecedented time, the quality of our first-quarter performance reflects strong demand for our portfolio of innovative products, continued commercial and clinical execution and the dedication and resilience of our employees around the world. The fundamentals of our business remain strong," said Kenneth C. Frazier, chairman and chief executive officer, Merck. "The COVID-19 global pandemic poses challenges to all of us, including serious threats to the health of people, businesses and economies around the world. Without question, our industry and our company have a unique ability and responsibility to help the world respond to this pandemic by working collaboratively to deliver solutions to coronavirus infection while also maintaining the supply of medically important products to those who need them."

GAAP (generally accepted accounting principles) earnings per share assuming dilution (EPS) was $1.26 for the first quarter of 2020. Non-GAAP EPS of $1.50 for the first quarter of 2020 excludes acquisition- and divestiture-related costs and restructuring costs.

COVID-19 Update

Overall, in response to the COVID-19 pandemic, Merck is focused on protecting the safety of its employees, ensuring that our supply of medicines and vaccines reach our patients, contributing our scientific expertise to the development of antiviral and vaccine approaches, and supporting health care providers and our communities. In addition, Merck is working diligently to continue its efforts to discover and develop new therapeutics to address society’s unmet medical needs, needs which persist despite the pandemic. Merck remains confident in the fundamental underlying demand for its products and its prospects for long-term growth, though COVID-related disruptions to patients’ ability to access health care providers will cause near-term challenges.

COVID-19 Research:

Building on our experience with antivirals and vaccines, we have embarked upon a broad-based development program for SARS-CoV-2. Merck has teams of scientists researching COVID-19 and assessing our available antiviral candidates and vaccine assets for potential to impact COVID-19. With respect to vaccines, Merck has been thoughtful in selecting proven platforms that have in the past been used to generate vaccines with desirable qualities. We are in advanced discussions with multiple groups, focusing on three different viral vaccine platforms. The details of those collaborations will be announced when the necessary arrangements are finalized. Beyond our search for vaccines, we also are engaged in studying potential antiviral therapies that could be deployed more rapidly. In addition to evaluating compounds in our own laboratories, we have identified programs in other laboratories that could prove beneficial.

The company also is engaged with a range of research organizations on collaborative efforts to accelerate the development of medicines and vaccines for COVID-19. Merck announced a new research collaboration with the Institute for Systems Biology to investigate and define the molecular mechanisms of SARS-CoV-2 infection and COVID-19 and identify targets for medicines and vaccines. In addition, we are participating in the NIH-led Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV consortium), a partnership that aims to develop a collaborative framework for prioritizing vaccine and drug candidates, streamlining clinical trials and regulatory processes and/or leveraging assets among all partners to rapidly respond to COVID-19 and future pandemics.

Business and Financial:

In the first quarter, the estimated overall impact of COVID-19 to Merck’s revenue was immaterial. For the full-year 2020, Merck expects an unfavorable impact to revenue of approximately $2.1 billion (excluding the impact of foreign exchange) due to COVID-19, comprised of approximately $1.7 billion for pharmaceuticals and approximately $400 million for Animal Health.

In the first quarter, within our human health business, markets in Asia Pacific, including China, saw a negative impact from social distancing measures and reduced access to health care providers given the earlier prevalence of the virus; whereas other markets, particularly in Europe, saw customers build inventory due to concerns about supply and ability to access health care providers given social distancing measures.

Roughly two-thirds of Merck’s pharmaceutical revenue is comprised of physician-administered products, which, despite strong underlying demand, are being impacted by social distancing measures, fewer well visits and delays in elective surgeries due to COVID-19. These impacts, as well as prioritization of COVID-19 patients at health care providers, are resulting in reduced administration of many of our human health products, in particular for our vaccines as well as KEYTRUDA (pembrolizumab) and IMPLANON/NEXPLANON (etonogestrel implant). The company anticipates reduced demand for its physician-administered products while pandemic-related access measures remain in place. In addition, declines in medical visits and elective surgeries also will have a negative impact on the demand for certain products, including BRIDION (sugammadex).

In our Animal Health business, revenue was positively impacted by approximately $60 million in the first quarter as customers made advance purchases to secure supply for livestock products and BRAVECTO (fluralaner), given the uncertainty related to expanding social distancing measures. The company expects that reduced veterinary visits and decreased protein and milk consumption due to restaurant and school closures will negatively impact the business going forward. Merck also expects that the negative impacts on the economy will have an additional unfavorable effect on its Animal Health business.

Operating expenses were positively impacted in the first quarter by approximately $100 million, primarily driven by lower promotional and selling costs and delayed clinical program spending due to COVID-19. For the full-year 2020, Merck expects a favorable impact to operating expenses of approximately $400 million.

While the company expects to rely on governmental authorities to determine when operations can return to normal and is cognizant that the duration, spread and severity of the outbreak will be critical determinants, for the purposes of the full-year estimates provided above, the company has assumed the majority of the negative impact will be in the second quarter, with a gradual return to normal operations beginning late in the second quarter and extending through the third quarter, with a full return to normal operations in the fourth quarter.

Merck’s financial strength and strong balance sheet is allowing it to continue with its capital allocation priorities, including investing in research and development (R&D) and in growth drivers, investing in manufacturing capacity expansion, paying its dividend and continuing the search for value-enhancing business development. However, given these priorities and the current operating environment, Merck has temporarily suspended its share repurchase program.

Merck’s updated 2020 guidance takes these impacts into consideration.

Clinical Trials:

Driven by our steadfast commitment to patients, we are making every effort to ensure that patients in affected areas who are enrolled in clinical trials are able to continue their treatment and receive appropriate care and monitoring. Conditions are fluid and evolving, but as local conditions allow, we are enrolling patients in ongoing studies, and we are starting new studies.

Manufacturing & Supply:

Continuity of supply of our medicines and vaccines to our patients and customers is a critical priority for Merck. To date, COVID-19 has not had a material impact on the production and supply of Merck’s medicines and vaccines. The company continues to have normal supply levels for most of its products, including KEYTRUDA and GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] / GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant), and doubled production capacity for ESMERON (rocuronium bromide), a muscle relaxant used for intubation in certain countries outside the U.S., to address a surge in market demand due to COVID-19. In general, Merck’s total supply chains are 6 to 12 months in length. The company currently believes supply of its medicines and vaccines will remain at normal levels through the pandemic.

Facilities and Employees:

The majority of Merck’s manufacturing plants and clinical supply sites are fully operational, and our laboratories are focused on essential operations. We are implementing steps to ensure business continuity. In many markets, including the U.S., while our offices and laboratories remain open, our colleagues are primarily working from home. In China, most of our offices, laboratories and plants are now open, although some of our office- and laboratory-based colleagues continue to work from home. In many markets, we have paused in-person interactions with health care providers and our field-based employees are working from home, including in the U.S.

Relief Efforts:

In addition to our efforts to ensure continuous supply of our medicines and vaccines to patients, as well as our research efforts aimed at finding a treatment or vaccine, Merck is engaged in several efforts to do our part in addressing the COVID-19 pandemic. We are actively supporting communities in various ways, including through product donations, personal protective equipment (PPE) donations and funding to relief organizations, including the United Nations Foundation’s COVID-19 Solidarity Response Fund in support of the World Health Organization and to the U.S. Centers for Disease Control and Prevention (CDC) Foundation Emergency Response Fund. In the U.S., we provided 800,000 surgical face masks for use as part of urgent efforts to address the outbreaks in New York and New Jersey. Through Merck for Mothers, the company’s global initiative to help end preventable maternal deaths, the company will provide funds to help health systems tackling COVID-19 better meet the needs of pregnant women before, during and following delivery. Recognizing the need for additional health care professionals, including doctors, nurses and medical laboratory technicians, to assist in regions where the virus is spreading, we announced a program to enable our medically trained employees to volunteer their time to aid their communities while maintaining their base pay. We also have taken a number of new steps to support patients in the U.S. who may have lost their jobs and insurance coverage during this crisis. The Merck Patient Assistance program will continue to ensure access to Merck medicines at no cost for eligible patients in the U.S. through a number of changes, which include assessing patients’ real-time financial situations and providing additional assistance with enrollments. In addition, changes to other U.S. access and assistance programs are being made due to the COVID-19 pandemic. We continue to consider other possible ways to support our communities as well as national and local relief efforts.

Oncology Pipeline Highlights

Merck continued to advance the development programs for KEYTRUDA, the company’s anti-PD-1 therapy; Lynparza (olaparib), a PARP inhibitor being co-developed and co-commercialized with AstraZeneca; and Lenvima (lenvatinib mesylate), an orally available tyrosine kinase inhibitor being co-developed and co-commercialized with Eisai Co., Ltd. (Eisai), in addition to other notable developments as follows:

Merck announced that the pivotal Phase 3 KEYNOTE-355 trial investigating KEYTRUDA in combination with chemotherapy met one of its dual primary endpoints of progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC) whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10). The trial continues to evaluate the other dual primary endpoint of overall survival (OS).
Merck announced that the Phase 3 KEYNOTE-204 trial evaluating KEYTRUDA for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) met one of its dual primary endpoints of PFS. Per the pre-specified analysis plan, the other dual primary endpoint of OS was not formally tested at this interim analysis; the study continues to evaluate OS.
Merck announced that the Phase 3 KEYNOTE-177 trial evaluating first-line treatment of KEYTRUDA in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer met one of its dual primary endpoints of PFS. The trial continues to evaluate the other dual primary endpoint of OS.
Merck announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a new supplemental Biologics License Application (sBLA) for KEYTRUDA seeking accelerated approval as monotherapy in patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) ≥10 mutations/megabase who have progressed following prior treatment and who have no satisfactory alternative treatment options. The application is based in part on results from the Phase 2 KEYNOTE-158 trial. The Prescription Drug User Fee Act (PDUFA) date is June 16, 2020.
Merck announced the resubmission of its sBLAs to the FDA seeking to update the dosing frequency for KEYTRUDA to include a 400 mg dose infused over 30 minutes every six weeks (Q6W), in addition to the currently approved dose of 200 mg every three weeks (Q3W). The sBLAs were filed across all adult indications for KEYTRUDA, including monotherapy and combination therapy.
Merck announced the U.S. launch of ONTRUZANT (trastuzumab-dttb), a biosimilar of the reference biologic medicine Herceptin, as part of a development and commercialization agreement with Samsung Bioepis.
Merck and AstraZenca announced further positive results from the Phase 3 PROfound trial evaluating Lynparza in men with metastatic castration-resistant prostate cancer (mCRPC) who have a homologous recombination repair gene mutation (HRRm) and whose disease had progressed on prior treatment with new hormonal agent (NHA) treatments (e.g. enzalutamide or abiraterone). Results from the trial showed a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS with Lynparza versus enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations.
Merck and AstraZeneca announced that the FDA has approved the kinase inhibitor Koselugo (selumetinib) for the treatment of pediatric patients two years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas.
Merck and AstraZeneca announced that the Phase 3 GY004 trial evaluating cediranib, an investigational oral vascular endothelial growth factor receptor (VEGFR) inhibitor, in combination with Lynparza versus platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer did not meet the primary endpoint of PFS.
Other Pipeline Highlights

Merck announced that ERVEBO (Ebola Zaire Vaccine, Live) has been registered by National Health Authorities in six African countries – Democratic Republic of the Congo (DRC), Burundi, Ghana, Guinea, Rwanda and Zambia – with approvals in additional countries in Africa anticipated in the near future.
Merck presented results from the Phase 3 VICTORIA study evaluating the efficacy and safety of vericiguat, an investigational soluble guanylate cyclase (sGC) stimulatory being jointly developed with Bayer AG, to treat patients with heart failure with reduced ejection fraction and following a worsening event. Results were presented at the virtual American College of Cardiology’s Annual Scientific Session together with World Congress of Cardiology and published simultaneously in The New England Journal of Medicine.
Merck announced that the pivotal Phase 3 trials (COUGH-1 and COUGH-2) evaluating the efficacy and safety of gefapixant, an investigational, orally administered, selective P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough met the primary efficacy endpoints for the gefapixant 45 mg twice daily treatment arms. The gefapixant 15 mg twice daily treatment arms did not meet the primary efficacy endpoint in either Phase 3 study.
Merck and Pfizer Inc.’s Phase 3 VERTIS CV cardiovascular (CV) outcomes trial for STEGLATRO (ertugliflozin), an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor, achieved its primary endpoint of non-inferiority for major adverse CV events (MACE) compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease. MACE was defined as time to the first event of CV death, nonfatal myocardial infarction or nonfatal stroke. The key secondary endpoints of superiority for STEGLATRO versus placebo for time to the composite of CV death or hospitalization for heart failure, CV death alone and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met. While not a pre-specified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed with STEGLATRO. The safety profile of STEGLATRO was consistent with that reported in previous studies. Detailed results of VERTIS CV are scheduled to be presented on June 16, 2020 at the virtual American Diabetes Association’s 80th Scientific Sessions.
Corporate Developments

Merck announced that Organon & Co. (Organon) will be the name of the new company to be created through the intended spinoff of its women’s health, trusted legacy brands and biosimilars businesses. We remain fully committed to our spinoff transaction, and we believe we are on track for completion in the first half of 2021.
Merck announced today its intention to consolidate our New Jersey campuses into a single New Jersey headquarters location in Rahway by the end of 2023.
First-Quarter Revenue Performance

Pharmaceutical Revenue

First-quarter pharmaceutical sales increased 10% to $10.7 billion, excluding the unfavorable effect from foreign exchange, sales grew 12%. The increase was driven primarily by growth in oncology and vaccines, partially offset by the ongoing impacts of the loss of market exclusivity for several products.

Growth in oncology was largely driven by higher sales of KEYTRUDA, which grew 45% to $3.3 billion for the quarter, reflecting strong momentum from the non-small cell lung cancer (NSCLC) indications as well as continued uptake in other indications, including renal cell carcinoma (RCC) and adjuvant melanoma. Additionally, oncology sales reflect alliance revenue of $145 million related to Lynparza and $128 million related to Lenvima, representing Merck’s share of profits, which are product sales net of cost of sales and commercialization costs.

Growth in vaccines in the first quarter was driven by higher sales of GARDASIL/GARDASIL 9 reflecting timing of shipments of approximately $120 million in China, timing of public sector purchases of approximately $70 million in the U.S., higher demand in China and Europe as well as pricing in the U.S. Growth was partially offset by the unfavorable effects of COVID-19 in certain markets, particularly in the U.S. and Hong Kong.

Growth in vaccines also was driven by PNEUMOVAX 23 (pneumococcal vaccine polyvalent), a vaccine to help prevent pneumococcal disease, reflecting higher demand in the U.S. and Europe primarily due to the COVID-19 pandemic.

Growth in vaccines was partially offset by lower sales of the pediatric vaccines VARIVAX (Varicella Virus Vaccine Live), a vaccine to help prevent chickenpox; and M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live), a vaccine to help prevent measles, mumps and rubella, primarily reflecting lower demand and the timing of government tenders in Latin America. As previously disclosed, Merck expects that full-year 2020 sales of VARIVAX will be lower than the prior year due in part to the timing of government tenders in select Latin American markets and that full-year 2020 U.S. sales of M-M-R II will be lower than the prior year driven by a decline in expected demand related to fewer measles outbreaks.

Performance in hospital acute care reflects higher demand globally, particularly in the U.S., for BRIDION, a medicine for the reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide in adults undergoing surgery, although the company anticipates demand will be negatively affected by reductions in elective surgeries due to COVID-19; and the ongoing launch of PREVYMIS (letermovir), a medicine for prophylaxis (prevention) of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant.

Pharmaceutical sales growth for the quarter was partially offset by the ongoing impacts from the loss of market exclusivity, including for NUVARING (etonogestrel/ethinyl estradiol vaginal ring), NOXAFIL (posaconazole), EMEND (aprepitant), VYTORIN (ezetimibe/simvastatin), CUBICIN (daptomycin) and REMICADE (infliximab). In addition, the decline in sales of JANUVIA (sitagliptin) and JANUMET (sitagliptin and metformin HCI) reflects continued pricing pressure in the U.S.

Animal Health Revenue

Animal Health sales totaled $1.2 billion for the first quarter of 2020, an increase of 18% compared with the first quarter of 2019; excluding the unfavorable effect from foreign exchange, Animal Health sales grew 21%. Growth in livestock products was due to the products acquired in the prior year Antelliq Corporation acquisition and COVID-19-related buy-in as described above. Growth in companion animal products was driven largely by demand for the BRAVECTO line of products for parasitic control due in part to COVID-19-related buy-in.

First-Quarter Expense, EPS and Related Information

GAAP Expense, EPS and Related Information

Gross margin was 72.5% for the first quarter of 2020 compared to 71.8% for the first quarter of 2019. The increase reflects favorable product mix and lower acquisition- and divestiture-related costs, partially offset by the unfavorable effects of royalties, manufacturing variances, pricing pressure, inventory write-offs, foreign exchange and restructuring costs.

Selling, general and administrative expenses were $2.6 billion in the first quarter of 2020, an increase of 5% compared to the first quarter of 2019. The increase primarily reflects higher acquisition- and divestiture-related costs, including costs related to the company’s planned spinoff of Organon, partially offset by lower promotion, selling and administrative costs due in part to the COVID-19 pandemic and the favorable effects of foreign exchange.

Research and development expenses were $2.2 billion in the first quarter of 2020, an increase of 14% compared with the first quarter of 2019. The increase was primarily driven by higher expenses related to clinical development, increased investment in discovery research and early drug development and higher licensing costs, partially offset by program and project delays and less travel and meetings due to the COVID-19 pandemic.

Other (income) expense, net, was $71 million of expense in the first quarter of 2020 compared to $188 million of expense in the first quarter of 2019, primarily reflecting income from investments in equity securities in 2020 compared with losses in 2019 and lower impairment charges, partially offset by higher net interest expense in 2020.

The effective income tax rate was 16.1% for the first quarter of 2020.

GAAP EPS was $1.26 for the first quarter of 2020 compared with $1.12 for the first quarter of 2019.

Non-GAAP Expense, EPS and Related Information

Non-GAAP gross margin was 75.5% for the first quarter of 2020 compared to 75.9% for the first quarter of 2019. The decrease in non-GAAP gross margin reflects the unfavorable effects of royalties, manufacturing variances, pricing pressure, inventory write-offs and foreign exchange, partially offset by favorable product mix.

Non-GAAP selling, general and administrative expenses were $2.3 billion in the first quarter of 2020, a decrease of 7% compared to the first quarter of 2019. The decrease primarily reflects lower promotion, selling and administrative costs due in part to the COVID-19 pandemic and the favorable effects of foreign exchange.

Non-GAAP R&D expenses were $2.2 billion in the first quarter of 2020, a 10% increase compared to the first quarter of 2019. The increase primarily reflects higher expenses related to clinical development, increased investment in discovery research and early drug development and higher licensing costs, partially offset by program and project delays and less travel and meetings due to the COVID-19 pandemic.

Non-GAAP other (income) expense, net, was $82 million of expense in the first quarter of 2020 compared to $21 million of expense in the first quarter of 2019, primarily reflecting higher net interest expense, partially offset by income from investments in equity securities in 2020 compared with losses in 2019.

The non-GAAP effective income tax rate was 17.0% for the first quarter of 2020.

Non-GAAP EPS was $1.50 for the first quarter of 2020 compared with $1.22 for the first quarter of 2019.

A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that followsFinancial Outlook

The full-year updated guidance that Merck is providing below includes the impact from the COVID-19 pandemic and the negative impact of foreign exchange, which is expected to be partially offset by the favorability from underlying business strength. While the company expects to rely on governmental authorities to determine when operations can return to normal and is cognizant that the duration, spread and severity of the outbreak will be critical determinants, for the purposes of the full-year 2020 guidance estimates, the company has assumed the majority of the negative impact will be in the second quarter, with a gradual return to normal operations beginning late in the second quarter and extending through the third quarter, with a full return to normal operations in the fourth quarter.

Merck lowered its full-year 2020 revenue range to be between $46.1 billion and $48.1 billion, including a negative impact from foreign exchange of approximately 2.5% at mid-April exchange rates.

Merck lowered its full-year 2020 GAAP EPS to be between $4.12 and $4.32. Merck lowered its full-year 2020 non-GAAP EPS to be between $5.17 and $5.37, including a negative impact from foreign exchange of approximately 3.5% at mid-April exchange rates. The non-GAAP range excludes acquisition- and divestiture-related costs and costs related to restructuring programs.

*The company does not have any non-GAAP adjustments to revenue.

**EPS guidance for 2020 assumes a share count (assuming dilution) of approximately 2.54 billion shares.

A reconciliation of anticipated 2020 GAAP EPS to non-GAAP EPS and the items excluded from non-GAAP EPS are provided in the table below.

Earnings Conference Call

Investors, journalists and the general public may access a live audio webcast of the call today at 8:00 a.m. EDT on Merck’s website at View Source Institutional investors and analysts can participate in the call (833) 353-0277 or toll free (469) 886-1947 and using ID code number 4589375. Members of the media are invited to monitor the call by dialing (833) 353-0277 or toll free (469) 886-1947 and using ID code number 4589375. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team at the conclusion of the call.

EORTC 1809 STRASS II trial in retroperitoneal sarcoma receives support by the Anticancer Fund

On April 28, 2020 EORTC reported that 1809 STRASS II trial in high-risk retroperitoneal sarcoma, an aggressive and rare cancer affecting the soft tissues of the body receives significant financial contribution by the Anticancer Fund (Press release, EORTC, APR 28, 2020, View Source [SID1234556673]). STRASS II is a randomized phase III study of chemotherapy followed by surgery versus surgery alone to improve disease control and survival in patients with high-risk retroperitoneal sarcoma.

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

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

                  Schedule Your 30 min Free Demo!

Retroperitoneal sarcoma is a very rare tumour, occurring in 0.5 to 1.0 per 100,000 of the population. Diagnosis and treatment are challenging. The standard of care consists currently of surgery. Overall survival at 5 years following surgery is between 60 and 70%. Histologic subtypes, like high grade dedifferentiated liposarcoma and leiomyosarcoma, originating from the retroperitoneum have a dismal prognosis with a risk of death above 70% at 5 years. The role of systemic therapy before or after surgery remains unproven and the policies of their use vary broadly among different institutions.

The Anticancer Fund is enthusiastic about this very first collaboration with the EORTC, an internationally renowned cancer research organisation. We launched a request for application in 2019 to support clinical trials aiming at reducing recurrence rate for cancer patients treated with curative intent. The EORTC 1809 STRASS II trial met all the criteria and was selected.

By funding this study we will contribute to an international randomised clinical trial in a cancer with a significant unmet need. ‘The allocation of research funds to areas with limited interest from the profit-driven cancer industry is essential to complement progress. With the EORTC we have the leading organisation in clinical research in Europe that works together with industry but also tries to address other patient-centred needs in a non-profit way. Especially these initiatives need encouragement’, explained Lydie Meheus, managing director of the Anticancer Fund.

The Anticancer Fund has been in regular contact with the EORTC and in 2019, both organisations endorsed each other’s manifesto, launched for the European Elections. ‘We are very pleased to partner with a like-minded organisation like the Anticancer Fund in addressing such an important question for patients with high-risk retroperitoneal sarcoma. For the EORTC, this marks the beginning of a successful partnership in tackling patient-centred questions where there is no industry involvement. ’ says Dr. Denis Lacombe, Director General of the EORTC.

Belgian entrepreneur Filip Balcaen, a major donor of the Anticancer Fund, encourages the enhanced collaboration between the Anticancer Fund and EORTC and describes it as a true milestone. ‘I’m convinced that organisations should join forces to achieve major breakthroughs in the fight against cancer’, he said.

The study

The EORTC 1809 STRASS II study is the first official trial looking into potential benefits of chemotherapy before surgery to improve disease control and survival in patients with retroperitoneal sarcoma, a rare and aggressive cancer with a low survival rate. STRASS II is a pan-European (13 countries) study with a transatlantic collaboration with multiple specialized sarcoma centers in Australia, Canada and North America. This collaboration recently completed inclusion of the first randomized controlled trial in retroperitoneal sarcoma ever, the STRASS trial examining the role of pre-operative radiotherapy in these tumours. In contrast to many other cancer types, an official trial looking into potential benefits of chemotherapy before surgery in these tumors has never been performed. 250 patients will be recruited over a period of 5.5 years. Additional follow-up of 1.5 years is expected to provide the targeted number of events for analysis. The study is coordinated by Dr. Alessandro Gronchi (Milan) and Dr. Winan van Houdt (Amsterdam).

With a total study cost for the EORTC of approximatively €2.9M, of which €1.4M is already secured, the Anticancer Fund will provide €700,000.

On the study’s importance, Dr Winan van Houdt said: ‘STRASS II is a breakthrough for a rare but devastating disease. It also emphasizes the importance of multinational collaborations in fighting rare cancers.’