On May 6, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported recent business highlights, anticipated upcoming milestones, and financial results for the first quarter of 2021 (Press release, BeiGene, MAY 6, 2021, View Source [SID1234579346]).

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"We continue to make excellent progress across the board in advancing our key strategic objectives, including enhancing our commercial scale in China, working to broaden access to our medicines around the world through new regulatory filings, advancing our pipeline, including potentially first-in-class compounds and wholly owned combinations, and expanding our capabilities in biologics manufacturing. We are encouraged by the performance of our commercial portfolio since the implementation on March 1 of three innovative oncology products in the National Reimbursement Drug List in China," said John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene. "In addition, we closed our license and collaboration agreement with Novartis, receiving a $650 million up-front payment, and recently announced positive interim results from our global Phase 3 head-to-head ALPINE trial in chronic lymphocytic leukemia, which we believe further demonstrates the differentiated and potentially best-in-class profile for BRUKINSA. We are confident in our strong position to deliver on our mission of providing high quality medicines to billions of more people around the world who need them."

Recent Business Highlights and Upcoming Milestones

Commercial Operations

Generated $106.1 million in global product revenue in the three months ended March 31, 2021, representing a 104% increase from $52.1 million in the comparable period of the prior year. Product sales in the first quarter grew over the prior year as well as sequentially compared to the prior quarter due to continued progress in our product launches, including significantly increased patient demand following the inclusion of tislelizumab, BRUKINSA, and XGEVA in the NRDL, effective March 1, 2021, which more than offset the net effect of price reductions as a result of NRDL inclusion;
First quarter product revenue grew sequentially despite a negative adjustment of $24.2 million as a result of the normal process in China of compensating distributors for products previously sold at the pre-NRDL price during the quarter that remained in the distribution channel, due to the first inclusion of tislelizumab, BRUKINSA, and XGEVA in the NRDL. The majority of the compensation related to tislelizumab;
Inclusion in the NRDL led to significant increases in the number of formal hospital listings for tislelizumab, BRUKINSA, and XGEVA to approximately 4x, 8x, and 6x their respective levels prior to NRDL inclusion; and
Sales of BRUKINSA in the United States continued steady growth despite the continued impact from COVID-19, including the vaccine rollout, on patient treatment plans.
Development Programs

BRUKINSA (zanubrutinib), a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects, approved in the United States, China, Canada, and other international markets in selected indications and under development for additional approvals globally.

Announced positive results from a planned interim analysis of the ongoing Phase 3 ALPINE trial (NCT03734016) comparing BRUKINSA against ibrutinib in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL);
Received approval and launched BRUKINSA in Canada for the treatment of adult patients with Waldenström’s macroglobulinemia (WM), based on the Phase 3 ASPEN trial comparing BRUKINSA and ibrutinib; and
Continued to advance BRUKINSA in new markets. BRUKINSA is now commercially available in Israel for patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering the European Union (EU) and more than 20 other countries.
Expected Milestones for BRUKINSA

Announce topline results from the Phase 3 SEQUOIA trial (NCT03336333) comparing BRUKINSA with bendamustine plus rituximab in patients with treatment-naïve CLL/SLL as early as 2021;
Present interim results from the Phase 3 ALPINE trial (NCT03734016) at a major medical conference in 2021 and announce additional results in 2022;
Continue to expand BRUKINSA’s registration program globally in new geographies and indications, including potential approvals in 2021 for certain patients with MCL in the Middle East, South America, Canada, Australia, and Russia; and with WM in the United States, EU, China, and Australia; and
Complete enrollment in the pivotal global Phase 2 ROSEWOOD trial (NCT03332017) comparing BRUKINSA and obinutuzumab versus obinutuzumab alone in patients with R/R follicular lymphoma (FL) in 2021.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China in selected indications and under development for additional approvals globally.

Entered into and closed a collaboration and license agreement with Novartis Pharma AG granting Novartis rights to develop, manufacture and commercialize tislelizumab in North America, Europe, and Japan, and received a $650 million up-front payment;
Announced the acceptance of a supplemental Biologics License Application (sBLA) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for treatment in the second- or third-line setting of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on prior platinum-based chemotherapy;
Initiated patient enrollment in the global Phase 2 clinical trial (NCT04716634) of tislelizumab in combination with HUTCHMED (China) Ltd.’s fruquintinib in solid tumors;
Completed enrollment in the Phase 3 trial (NCT04005716) of tislelizumab with or without platinum chemotherapy plus etoposide in patients with untreated extensive-stage small cell lung cancer; and
Announced clinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 from the planned interim analysis of the Phase 3 RATIONALE 303 trial (NCT03358875) of tislelizumab compared to docetaxel as second- or third-line therapy for patients with locally advanced or metastatic NSCLC in an oral presentation.
Expected Milestones for Tislelizumab

Submit the first biologics license applications (BLA) outside of China in 2021 in collaboration with Novartis;
Submit sBLAs in China for MSI-H/dMMR solid tumors in the first half of 2021, and for second-line esophageal squamous cell carcinoma (ESCC) in mid-2021;
Receive approvals in first-line non-squamous NSCLC and second/third-line hepatocellular carcinoma (HCC) in China in 2021;
Present clinical data at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, including posters on:
– the RATIONALE 302 trial (NCT03430843) of tislelizumab versus chemotherapy as a second-line treatment for advanced unresectable ESCC; and

– the Phase 2 clinical trial (NCT03736889) of tislelizumab as monotherapy in patients with previously treated, locally advanced unresectable or MSI-high/MRD solid tumors;

Announce topline results of the Phase 3 trial (NCT03924986) of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NPC) in 2021; and
Complete enrollment in the Phase 3 trial (NCT03957590) of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC in 2021.
Pamiparib, an investigational selective small molecule inhibitor of PARP1 and PARP2

Expected Milestones for Pamiparib

Receive approval in China for the treatment of patients with germline BRCA mutation-associated advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy, in the first half of 2021;
Announce topline results from the Phase 3 trial (NCT03519230) of pamiparib as a maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer (OC) in 2021 or the first half of 2022; and
Present clinical data at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, including posters on:
– the Phase 2 trial (NCT03575065) in China of pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation; and

– the Phase 2 clinical trial (NCT03427814) of pamiparib versus placebo as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer that responded to platinum-based first-line chemotherapy.

Ociperlimab (BGB-A1217), an investigational TIGIT monoclonal antibody with competent Fc function

Initiated patient enrollment in the following trials:
– the Phase 2 AdvanTIG-202 trial (NCT04693234) of ociperlimab in combination with tislelizumab in patients with previously treated recurrent or metastatic cervical cancer; and

– the Phase 2 AdvanTIG-203 trial (NCT04732494) of ociperlimab in combination with tislelizumab versus tislelizumab in combination with placebo for the second-line treatment of patients with unresectable, locally advanced, recurrent or metastatic ESCC whose tumors have high PD-L1 expression.

Expected Milestones for Ociperlimab

Present clinical data at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting on the Phase 1 dose-escalation study (NCT04047862) of ociperlimab in combination with tislelizumab in patients with advanced solid tumors;
Initiate patient enrollment in the global Phase 3 AdvanTIG-302 trial (NCT04746924) of ociperlimab in combination with tislelizumab for the first-line treatment of patients with locally advanced, unresectable, or metastatic NSCLC whose tumors have high PD-L1 expression and do not harbor EGFR-sensitizing mutations or ALK translocations, in the first half of 2021; and
Initiate patient enrollment in the global Phase 3 AdvanTIG-301 trial (NCT04866017) of ociperlimab in combination with tislelizumab and concurrent chemoradiotherapy, in patients with previously untreated, locally advanced unresectable NSCLC in 2021.
Early-Stage Programs

Announced that the first patient was dosed in a Phase 1 clinical trial (NCT04649385) of BGB-15025, an investigational hematopoietic progenitor kinase 1 (HPK1) inhibitor that is designed to be a potent and highly selective small molecule oral inhibitor of HPK1 and is among the first HPK1 inhibitors to enter the clinic, representing a novel immuno-oncology approach; and
Continued to advance our early-stage clinical pipeline of internally-developed product candidates, including BGB-11417 (BCL-2 inhibitor in Phase 1 development for cancer), BGB-A445 (non-ligand competing OX40 monoclonal antibody in Phase 1 development in combination with tislelizumab for solid tumors), and BGB-10188 (PI3Kδ inhibitor in Phase 1 development in combination with BRUKINSA or tislelizumab for cancer).
Expected Milestones for Early-Stage Programs

Initiate a Phase 1 trial (NCT04771130) for BGB-11417, BeiGene’s investigational BCL-2 inhibitor, in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in 2021. BGB-11417 has been designed to be a potent and selective small molecule Bcl-2 inhibitor; and
Initiate the Phase 2 portion of the Phase 1/2 trial (NCT03744468) of BGB-A425 in the first half of 2021.
Collaboration with Amgen

Received acceptance of a sBLA and priority review in China of BLINCYTO (blinatumomab) for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Other Collaboration Programs

Sitravatinib, an investigational tyrosine kinase inhibitor of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET, licensed from Mirati Therapeutics Inc. (Mirati), in Asia (excluding Japan), Australia, and New Zealand.

Announced clinical data at AACR (Free AACR Whitepaper) on the combination of tislelizumab with sitravatinib, being jointly developed with Mirati, in two oral presentations from two cohorts of a Phase 1b trial (NCT03666143), in patients with unresectable or metastatic melanoma who were refractory or resistant to PD-1/L1 inhibitors, and in patients with advanced platinum-resistant ovarian cancer (PROC); and
Completed enrollment in the Phase 1/2 trial (NCT03941873) of sitravatinib as monotherapy and in combination with tislelizumab in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) or gastric/gastroesophageal junction cancer (GC/GEJC).
Expected Milestones for Sitravatinib

Initiate a Phase 3 trial of sitravatinib in combination with tislelizumab in squamous and non-squamous NSCLC in 2021.
Manufacturing Operations

Announced approval from the NMPA to begin manufacturing commercial supply of tislelizumab at our state-of-the-art biologics facility in Guangzhou, China. At over one million square feet (100,000 square meters) and 8,000 liters of biologics capacity approved for commercial supply, this wholly owned facility has begun production and distribution of commercial supply of tislelizumab for the China market. An additional phase of construction currently in progress to bring total capacity to 64,000 liters is expected to be completed by the end of 2022.
COVID-19 Impact and Response

The Company expects that the worldwide health crisis of COVID-19 will continue to have a negative impact on its operations, including commercial sales, regulatory interactions, inspections, filings, and clinical trial recruitment, participation, and data read outs. There remains uncertainty regarding the future impact of the pandemic globally. The Company is striving to minimize delays and disruptions, and continues to execute on its commercial, regulatory and clinical development goals globally.
Corporate Developments

Announced that Julia Wang has been appointed Chief Financial Officer, effective June 30, 2021. Ms. Wang will succeed Howard Liang, Ph.D., who previously announced his intention to retire from BeiGene and who will stay on through June 30 to ensure an orderly transition; and
Continued to work on our filing for a proposed public offering and listing of the Company’s ordinary shares on the Science and Technology Innovation Board (STAR Market) of the Shanghai Stock Exchange, which is expected to be completed in 2021, subject to market conditions, shareholder approval, and regulatory approvals.
First Quarter 2021 Financial Results

Cash, Cash Equivalents, Restricted Cash, and Short-Term Investments were $4.8 billion as of March 31, 2021, compared to $4.7 billion as of December 31, 2020, representing an increase of $162.1 million.

In the three months ended March 31, 2021, cash provided by operating activities was $125.1 million, which included $650.0 million received as an upfront payment from the collaboration agreement with Novartis; capital expenditures were $42.4 million; cash used for upfront license payments was $8.5 million; and cash provided by financing activities was $107.4 million, consisting primarily of bank loans and the exercise of employee share options.
Revenue for the three months ended March 31, 2021 was $605.9 million, compared to $52.1 million in the same period of 2020.

Product revenues totaled $106.1 million for the three months ended March 31, 2021, compared to $52.1 million in the same period of 2020, and comprised:
– Sales of tislelizumab in China of $48.9 million, compared to $20.5 million in the prior year period;

– Sales of BRUKINSA of $22.1 million, compared to $0.7 million in the prior year period;

– Sales of XGEVA, the first product transferred to BeiGene from the Amgen collaboration, in China of $14.5 million. BeiGene commenced sales and marketing in China in July 2020;

– Sales of Bristol Myers Squibb (BMS) in-licensed products in China of $20.3 million, compared to $30.8 million in the same period of the prior year. The reduction in the current year period is due primarily to the lack of product sales of ABRAXANE following the suspension by the NMPA and voluntary recall by BMS in March 2020; and

Collaboration revenue for the three months ended March 31, 2021 was $499.8 million, resulting primarily from the partial recognition of the upfront payment of $650.0 million from Novartis. There was no collaboration revenue for the prior year period.
Expenses for the three months ended March 31, 2021 were $535.7 million, compared to $425.8 million in the same period of 2020.

Cost of Sales for the three months ended March 31, 2021 were $32.7 million, compared to $14.1 million in the same period of 2020. Cost of sales increased due to increased product sales of tislelizumab, BRUKINSA and XGEVA, and were partially offset by lower sales of BMS in-licensed products.
R&D Expenses for the three months ended March 31, 2021 were $320.7 million, compared to $304.3 million in the same period of 2020. The increase in R&D expenses was primarily attributable to continued increases in spending on our ongoing and late-stage pivotal clinical trials, the preparation for additional regulatory submissions, and manufacturing costs related to development programs and pre-commercial activities. Upfront fees related to in-process R&D for in-licensed product candidates decreased $34.5 million to $8.5 million for the three months ended March 31, 2021, compared to $43.0 million for the same period of 2020. R&D-related share-based compensation expense was $21.9 million for the three months ended March 31, 2021, compared to $20.4 million for the same period of 2020.
SG&A Expenses for the three months ended March 31, 2021 were $182.1 million, compared to $107.1 million in the same period of 2020. The increase in SG&A expenses was primarily attributable to increased headcount and increased external expenses related to the growth of our global commercial organization, as we continue to build our worldwide footprint. SG&A-related share-based compensation expense was $23.9 million for the three months ended March 31, 2021, compared to $17.9 million for the same period of 2020.
Net Income for the three months ended March 31, 2021 was $66.5 million, compared to a net loss of $363.7 million in the prior year period. For the three months ended March 31, 2021, basic and diluted earnings per share were $0.06 and $0.05, respectively, and basic and diluted earnings per American Depositary Share (ADS) were $0.73 and $0.69, respectively. For the three months ended March 31, 2020, net loss per share was $0.36 per share, or $4.70 per ADS.

[1] Research and development expense for the first quarter ended March 31, 2021 and 2020 includes upfront fees related to in-process research and development of in-licensed assets totaling $8.5 million and $43.0 million, respectively.

On May 6, 2021 NGM Biopharmaceuticals, Inc. (NGM) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, reported financial results for the period ending March 31, 2021 (Press release, NGM Biopharmaceuticals, MAY 6, 2021, View Source [SID1234579363]).

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"In the first quarter of 2021, we achieved a key milestone in our oncology portfolio with the initiation of the randomized, placebo-controlled component of our NGM120 study in patients with metastatic pancreatic cancer," said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM. "We also continued to make progress across our four other ongoing Phase 2 and Phase 2b programs. We remain on track to report topline data from our Phase 2b ALPINE 2/3 clinical study of aldafermin in patients with NASH in the second quarter and we expect to complete enrollment in our Phase 2 CATALINA clinical study of NGM621 in patients with geographic atrophy by mid-year. Our team continues to work diligently to advance our two lead immuno-oncology product candidates into the clinic later this year."

Dr. Woodhouse continued, "We demonstrated strong pipeline and corporate execution despite the continued challenges presented by the COVID-19 pandemic and continue to focus on our mission to translate powerful biology with urgency and rigor to deliver life-changing medicines."

Key First Quarter and Recent Highlights

Liver and metabolic diseases

Anticipate reporting topline data from the Phase 2b ALPINE 2/3 study of aldafermin in patients with NASH with liver fibrosis stage 2 or 3 (F2-F3) in the second quarter. ALPINE 2/3 is a Phase 2b clinical study of aldafermin in patients with biopsy-confirmed NASH and liver fibrosis F2 or F3. The 24-week study will assess the efficacy, safety and tolerability of 0.3 mg, 1 mg and 3 mg doses of aldafermin compared to placebo. The primary objective of the ALPINE 2/3 study is to evaluate a dose response showing an improvement in liver fibrosis by ≥ 1 stage with no worsening of steatohepatitis at week 24.
Continued enrollment in Phase 2b ALPINE 4 study of aldafermin in patients with NASH with liver fibrosis stage 4 (F4) and compensated cirrhosis. NGM continued enrollment in the Phase 2b ALPINE 4 clinical study of aldafermin in patients with biopsy-confirmed NASH with F4 liver fibrosis and compensated cirrhosis. The 48-week study is designed to enroll approximately 160 patients and will assess the efficacy, safety and tolerability of 0.3 mg, 1 mg and 3 mg doses of aldafermin compared to placebo. The primary objective of ALPINE 4 is to evaluate a dose response showing an improvement in liver fibrosis by ≥ 1 stage with no worsening of steatohepatitis at week 48.
Merck continued the Phase 2b study of MK-3655 in patients with NASH with F2-F3 liver fibrosis. In November 2020, Merck initiated a global Phase 2b multicenter study of MK-3655 for the treatment of F2-F3 NASH. The 52-week randomized, double-blind study is designed to enroll approximately 320 patients and will assess the efficacy, safety and tolerability of 50 mg, 100 mg and 300 mg doses of MK-3655 compared to placebo. The primary objective of the Phase 2b study is NASH resolution without worsening of fibrosis after 52 weeks. Merck licensed MK-3655 following NGM’s completion of a proof-of-concept study. NGM retains an option, at the initiation of the first Phase 3 clinical trial for MK-3655, to either receive milestone and royalty payments or to co-fund development and participate in a global cost and revenue sharing arrangement of up to 50% for MK-3655.
Retinal diseases

Expect to complete enrollment in the Phase 2 CATALINA study of NGM621 in patients with GA by mid-year. NGM continues to enroll patients in the Phase 2 CATALINA study, a multi-center, randomized, double-masked, sham-controlled clinical trial to evaluate the safety and efficacy of intravitreal (IVT) injections of NGM621 every four weeks or every eight weeks in patients with geographic atrophy (GA) in one or both eyes secondary to age-related macular degeneration. NGM anticipates completing enrollment by mid-year. The primary endpoint is the rate of change in GA lesion area, as measured by fundus autofluorescence imaging, over 52 weeks of treatment.
Presented Phase 1 safety and pharmacokinetics (PK) data for NGM621 in patients with GA at the Angiogenesis, Exudation, and Degeneration 2021 – Virtual Edition. Single and multiple IVT injections of NGM621 appeared safe and well tolerated in this first-in-human study, with no patients experiencing serious adverse events, drug-related adverse events, endophthalmitis, intraocular inflammation or choroidal neovascularization. The serum PK of NGM621 was linear and dose-proportional. Based on ocular PK/pharmacodynamics (PD) modeling, NGM believes NGM621 has the potential for up to an every eight-week dosing regimen.
Cancer

Initiated a Phase 2 placebo-controlled component of an ongoing Phase 1/2 study of NGM120 in January, testing NGM120 as a first-line treatment in combination with gemcitabine and Abraxane (paclitaxel protein bound) in patients with metastatic pancreatic cancer. NGM initiated a multi-center, randomized, single-blind (sponsor unblinded), placebo-controlled component of NGM120 in combination with gemcitabine and Abraxane as a first line treatment in patients with metastatic pancreatic cancer as part of its ongoing Phase 1/2 trial. This Phase 2 component of the Phase 1/2 study is designed to enroll approximately 60 patients and will assess the efficacy, safety and tolerability of NGM120 or placebo in combination with gemcitabine and Abraxane against both cancer and cancer-related cachexia endpoints. The Phase 1a/1b dose-finding portion of the study is still ongoing, and NGM expects to report interim results from that portion of the study in the second half of the year.
Continued to progress two new oncology clinical candidates, NGM707 and NGM438, toward the clinic. These programs are part of NGM’s strategy to treat cancer through myeloid reprogramming that reverses immune suppression in the tumor microenvironment. NGM707 is a dual antagonist antibody that inhibits Immunoglobulin-like transcript 2 (ILT2) and Immunoglobulin-like transcript 4 (ILT4). NGM438 is an antagonist antibody that inhibits Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1). NGM expects to initiate a first-in-human Phase 1 trial for NGM707 in patients with advanced solid tumors in mid-2021 and for NGM438 in patients with advanced solid tumors during the fourth quarter.
Corporate

Completed a public offering of common stock. In January, NGM completed an underwritten public offering of 5,324,074 shares of its common stock for net proceeds to NGM of $134.6 million, which included the full exercise by the underwriters of their over-allotment option to purchase additional shares, at a price to the public of $27.00 per share.
Nomination of Roger M. Perlmutter for election to Board of Directors. On April 28, 2021, NGM announced that the company has nominated Roger M. Perlmutter, M.D., Ph.D. to stand for election to the company’s board of directors at its June 8, 2021 annual meeting of stockholders. Dr. Perlmutter brings decades of expertise and renowned leadership in drug discovery and development with global healthcare companies including Merck and Amgen.
Extended deadline for Merck collaboration extension notice. Merck has a unilateral option to extend the research and early development phase of its ongoing strategic collaboration with NGM, which would, if exercised by Merck, extend the research phase of the collaboration for an additional two-year period from March 2022 to March 2024. Merck was required to notify NGM of its unilateral decision whether to exercise its option in March 2021, but in order to allow the parties to negotiate potential modifications to the terms of the collaboration agreement, on March 12, 2021, Merck and NGM agreed to extend the deadline for Merck’s decision until June 30, 2021. NGM expects that any modified collaboration would result in a level of annual research support from Merck during any extension of the current research phase after March 2022 that is meaningfully lower than the annual research support Merck provided NGM during the initial five-year term and the first extension period. NGM also expects that if Merck and NGM are unable to reach agreement on modified terms, Merck will not elect to extend the research phase of the collaboration and that NGM’s obligation to fund its own research and development efforts will substantially increase after March 2022.
First Quarter 2021 Financial Results

NGM reported a net loss of $27.5 million for the quarter ended March 31, 2021, compared to a net loss of $19.1 million for the same period in 2020.
Related party revenue from our collaboration with Merck was $21.6 million for the quarter ended March 31, 2021, compared to $24.4 million or the same period in 2020. The decrease in related party revenue of $2.8 million in 2021 was primarily attributable to a decrease in the recognition of the initial upfront payment received from Merck in 2015 that was included in the transaction price and fully recognized by March 2020.
Research and development, or R&D, expenses were $40.7 million for the quarter ended March 31, 2021, compared to $38.4 million for the same period in 2020. R&D expenses increased $2.3 million in 2021, primarily due to a $3.5 million increase in personnel-related expenses and an increase in external expenses driven by our ongoing clinical and pre-clinical studies of NGM621, NGM438 and NGM707. These increases were partially offset by a decrease of $4.6 million in our manufacturing activities and ongoing clinical trials of aldafermin and $1.2 million in external expenses related to our other development programs.
General and administrative expenses were $8.7 million for the quarter ended March 31, 2021, compared to $6.6 million for the same period in 2020. The $2.1 million increase in general and administrative expenses in 2021 was primarily attributable to increases in personnel-related expenses driven by increased headcount, as well as external expenses to support our operations as a public company.
Cash, cash equivalents and short-term marketable securities were $412.7 million as of March 31, 2021, compared to $295.2 million as of December 31, 2020.
Merck Collaboration

Under the current terms of NGM’s collaboration with Merck, Merck has a one-time option to license NGM pipeline programs – other than aldafermin, NGM386 and NGM395 – following human proof-of-concept trials under the terms of the companies’ ongoing strategic collaboration. Upon exercising any such option, Merck would lead global product development and commercialization for the resulting products, if approved. Prior to Merck initiating a Phase 3 study for a licensed program, NGM may elect to either receive milestone and royalty payments or to co-fund development and participate in a global cost and revenue share arrangement of up to 50%. The current terms of the collaboration also provide NGM with the option to participate in the co-promotion of any co-funded program in the United States. In January 2019, Merck exercised its first option under the collaboration to license MK-3655, previously referred to as NGM313. As described above, the parties continue to negotiate potential modifications to the terms of the collaboration.

On May 6, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that a conference call will be held on Monday, May 10, 2021 at 8:30 AM ET to discuss results for the first quarter 2021 and provide a business outlook for 2021. Michael S. Weiss, Executive Chairman and Chief Executive Officer, will host the call (Press release, TG Therapeutics, MAY 6, 2021, https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-host-conference-call-first-quarter-2021 [SID1234579379]).

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In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at www.tgtherapeutics.com. An audio recording of the conference call will also be available for a period of 30 days after the call.

TG Therapeutics will announce its financial results for this period in a press release to be issued prior to the call.

On May 6, 2021 Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported financial results and provided business updates for the first quarter 2021 and highlighted pipeline progress (Press release, Moderna Therapeutics, MAY 6, 2021, View Source;text=%E2%80%9CBased%20on%20these%20first%20quarter,2021%20to%20800%20million%20doses. [SID1234579396]).

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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

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"In the first quarter, the Moderna team delivered on its supply commitments to many governments and helped protect more than 100 million people. This accomplishment translated into our first profitable quarter in the company’s history, after 10 years of scientific innovation and several billion dollars invested to make our mRNA platform a reality," said Stéphane Bancel, Chief Executive Officer of Moderna. "Based on these first quarter accomplishments and our current manufacturing scale-up trajectory, we were pleased to again increase our base plan for 2021 to 800 million doses. The Moderna team and our manufacturing partners are working hard to get as close to 1 billion doses in 2021 as we can. The feedback from governments around the world requesting high-efficacy mRNA vaccines and variant boosters is overwhelming. We are now actively engaged in discussions and agreements for 2022 with all of the governments we are currently supplying for 2021. On top of that, new partnerships, like COVAX, for up to 466 million doses in 2022 and discussions with new governments in Asia, Middle East, Africa and Latin America, make us believe that our total advance purchase agreements for 2022 should be higher than those in 2021."

New updates and recent progress include:

COVID-19 Vaccine Development

Increased 2021 supply forecast to between 800 million and 1 billion doses; making additional investments to increase global supply for COVID-19 Vaccine to up to 3 billion doses in 2022 (depending on the mix)
Company recently announced data supporting 3-month refrigerated (2-8°C) stable formulation
New data shows a single booster dose of 50 µg of mRNA-1273 or mRNA-1273.351 increased neutralizing titers against SARS-CoV-2 and two variants of concern (B.1.351, P.1) in previously vaccinated clinical trial participants
Initial analysis of Phase 2/3 TeenCOVE study of mRNA-1273 in adolescents ages 12 to 17 years showed vaccine efficacy against COVID-19 of 96%; mRNA-1273 was generally well tolerated with no serious safety concerns identified to date
Phase 3 study of mRNA-1273 in adults with a kidney or liver transplant is ongoing
Company plans to initiate rolling submission for BLA in the U.S. this month
Infectious Diseases

Positive interim data from Phase 1 study of RSV vaccine candidate (mRNA-1345) in younger adults (ages 18-49 years)
Positive seven-month interim data from Phase 2 study of cytomegalovirus (CMV) vaccine candidate (mRNA-1647) announced during Vaccines Day on April 14; Moderna preparing for pivotal Phase 3 study expected to begin in 2021
Rare Diseases

First patient dosed in Propionic Acidemia (mRNA-3927) Phase 1/2 Paramount study
Moderna currently has 24 mRNA development programs in its portfolio with 14 having entered clinical studies. The Company’s updated pipeline can be found at www.modernatx.com/pipeline. Moderna and collaborators have published more than 65 peer-reviewed papers.

Summary of Program Highlights by Modality

Core Modalities

Prophylactic Vaccines: Moderna is developing vaccines against viral diseases where there is unmet medical need – including complex vaccines with multiple antigens for common diseases, as well as vaccines against threats to global public health. The Company’s global public health portfolio is focused on epidemic and pandemic diseases for which funding has been sought from governments and non-profit organizations.

COVID-19 Vaccine Development

Moderna COVID-19 Vaccine: The Company shared an update on the Phase 3 COVE study of the Moderna COVID-19 Vaccine (mRNA-1273) at its annual Vaccines Day on April 14, 2021. An updated review of adjudicated cases identified over 900 cases of COVID-19 in the COVE study as of April 9th, including over 100 cases of severe COVID-19, as defined in the protocol, with a median follow-up of approximately 6 months post dose 2. Vaccine efficacy starting two weeks following the second dose and based on the updated adjudicated cases remains consistent with prior updates, including greater than 90% efficacy against all cases of COVID-19, and greater than 95% efficacy against severe cases of COVID-19. The COVE study is ongoing and reported results remain preliminary. Throughout the year, Moderna will be sharing updated data from the Phase 3 COVE study including efficacy against asymptomatic infection, genotyping data, additional antibody persistence data and information regarding potential correlates of protection. Moderna has also received emergency (or other conditional, interim or provisional) authorization for use of its COVID-19 vaccine from health agencies in Canada, Israel, the European Union, the United Kingdom, Switzerland, Singapore, Qatar, Taiwan, the World Health Organization (WHO), and the Philippines. The Company plans to initiate rolling submission for a Biologics License Application (BLA) for the vaccine in the U.S. this month. Moderna is working with additional health agencies on the authorization of its vaccine in additional jurisdictions. BARDA, part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), partially supported the research and development of the Moderna COVID-19 Vaccine with federal funding under Contract no. 75A50120C00034. Moderna retains worldwide rights to develop and commercialize the Moderna COVID-19 Vaccine.

Temperature Stability Update: Moderna recently announced that ongoing development data related to the current formulation of the Moderna COVID-19 Vaccine (mRNA-1273) could support a 3-month refrigerated (2-8°C) shelf life for the vaccine in alternative formats to facilitate easier distribution to doctor’s offices and other smaller settings, if authorized. Currently, the Moderna COVID-19 Vaccine is approved for storage up to 1 month at refrigerated temperatures (2-8°C) and up to 7 months in a standard freezer (-20°C). The Moderna COVID-19 Vaccine is also the only authorized mRNA vaccine that does not require on-site dilution. The Company also announced that it is working on formulations of mRNA-1273 and a next generation vaccine (mRNA-1283) that it believes will extend refrigerated shelf life even further.
Publication of Note: Antibody persistence data out to 6 months following the second dose of the Moderna COVID-19 Vaccine were recently published in The New England Journal of Medicine. This study analyzed 33 healthy adult participants in the NIH-led Phase 1 study of Moderna’s COVID-19 Vaccine at 6 months following the second 100 μg dose (day 209). As detected by three distinct serologic assays, antibodies elicited by the Moderna COVID-19 Vaccine persisted through 6 months after the second dose. Antibody decay was estimated using two approaches and was consistent with published observations of convalescent patients with COVID-19 through 8 months after symptom onset.

Addressing Variants of Concern: On February 24, Moderna announced that it completed manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant known as B.1.351 first identified in the Republic of South Africa and has shipped doses to the NIH for a Phase 1 clinical trial that will be led and funded by the NIH’s NIAID. The Company also provided an update on its strategy for addressing SARS-CoV-2 variants of concern.
Publication of Note: Initial data from Moderna’s Phase 2 study showed that a single 50 µg dose of mRNA-1273 or mRNA-1273.351 given as a booster to previously vaccinated individuals increased neutralizing antibody titer responses against SARS-CoV-2 and two variants of concern, B.1.351 (first identified in South Africa) and P.1 (first identified in Brazil). A booster dose of mRNA-1273.351, the Company’s strain-matched booster, achieved higher neutralizing antibody titers against the B.1.351 variant of concern than a booster dose of mRNA-1273. Safety and tolerability profiles following third dose booster injections of 50 µg of mRNA-1273 or mRNA-1273.351 were generally comparable to those observed after the second dose of mRNA-1273 in the previously reported Phase 2 and Phase 3 studies.
Publication of Note: Preclinical data on the Company’s variant booster vaccine candidates have been submitted as a preprint to bioRxiv showed that both mRNA-1273.351 and mRNA-1273.211 increase neutralizing titers against SARS-CoV-2 variants of concern in mice. Specifically, this preclinical data confirms improved neutralizing titers with the mRNA-1273.351 vaccine primary series. The multi-valent vaccine provided the broadest level of immunity. A boost at 6 months with mRNA-1273.351 closed the neutralizing titer gap for the variants of concern. Following the mRNA-1273.351 boost, neutralizing titers were comparable between the ancestral strain (Wuhan) and the new B.1.351 variant.
Further Clinical Studies of mRNA-1273
Phase 2/3 "TeenCOVE" study of mRNA-1273 in adolescents: The Phase 2/3 study of mRNA-1273 in adolescents ages 12-17 years has completed enrollment in the U.S. An initial analysis of 3,235 participants randomized 2:1 in TeenCOVE Study showed a vaccine efficacy rate of 96% in seronegative participants who received at least one injection. The analysis included 12 cases starting 14 days after first dose and based on the CDC definition of COVID-19, which requires one COVID-19 symptom and paired with a nasopharyngeal (NP) swab or saliva sample positive for SARS-CoV-2 by RT-PCR. Because the incidence rate of COVID-19 is lower in adolescents, the case definition is less stringent than for COVE, resulting in vaccine efficacy against milder disease. The median duration for follow-up in this initial analysis was 35 days following the second dose. mRNA-1273 was generally well tolerated. The majority of adverse events were mild or moderate in severity. No serious safety concerns have been identified to date. The most common solicited local adverse event was injection site pain. The most common solicited systemic adverse events after the second dose of mRNA-1273 were headache, fatigue, myalgia and chills. The Company is continuing to collect data in TeenCOVE and is in discussions with regulators about a potential amendment to its regulatory filings.
Phase 2 "KidCOVE" study of mRNA-1273 in young children: The Phase 2 study of mRNA-1273 in pediatric population ages 6 months to 11 years is ongoing.

Phase 1/2 study of mRNA-1273 in Japan: The Phase 1/2 study of Moderna’s vaccine candidate against COVID-19 (mRNA-1273 or TAK-919) in Japan, led by Takeda Pharmaceutical Co., Ltd is ongoing.

Phase 3 "COVE Transplant" study of mRNA-1273: The Phase 3 study of mRNA-1273 in adults with a kidney or liver transplant is ongoing.
Next-generation vaccine against COVID-19 (mRNA-1283): The Phase 1 study of mRNA-1283 is ongoing. mRNA-1283 is a next-generation vaccine candidate against COVID-19 that encodes for the portions of the SARS-CoV-2 spike protein critical for neutralization, specifically the Receptor Binding Domain (RBD) and N-terminal Domain (NTD). The encoded mRNA-1283 antigen is shorter than mRNA-1273 and is being developed as a potential refrigerator stable mRNA vaccine that will facilitate easier distribution and administration by healthcare providers. mRNA-1283 is intended to be evaluated for use as a booster dose for previously vaccinated or infected individuals as well as in a primary series for seronegative individuals.

Vaccines requiring complex antigens and against highly prevalent infections

Cytomegalovirus (CMV) vaccine (mRNA-1647): Positive seven-month data from the Phase 2 study assessing the safety, reactogenicity, and immunogenicity of different dose levels (50 μg, 100 μg and 150 μg) of mRNA-1647 were presented at Moderna’s annual Vaccines Day on April 14, 2021. mRNA-1647 was generally well tolerated. The most common solicited local adverse reaction (AR) was injection site pain and the most common solicited systemic ARs were headache, fatigue, myalgia, arthralgia and chills. Rates of Grade 3 solicited ARs after the third vaccination were similar to, or lower than the rates of Grade 3 solicited ARs after the second vaccination. In CMV-seronegative participants in mRNA-1647 treatment groups after the third vaccination, neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were at least 20-fold higher than the baseline GMT of the CMV-seropositive group and neutralizing antibody GMTs against fibroblast infection approximated the baseline GMT of the CMV-seropositive group. In CMV positive participants in mRNA-1647 treatment groups after the third vaccination: neutralizing antibody GMTs against epithelial cell infection increased to at least 6.8-fold over baseline and neutralizing antibody GMTs against fibroblast infection increased to approximately 2-fold over baseline. Based on the interim analysis of the Phase 2 study, the 100 μg dose has been chosen for the Phase 3 pivotal study, which is expected to begin in 2021. Moderna owns worldwide commercial rights for mRNA-1647.

Epstein-Barr virus (EBV) vaccine (mRNA-1189): mRNA-1189 is a vaccine against EBV containing five mRNAs that encode viral proteins (gp350, gB, gp42, gH and gL) in EBV. Similar to Moderna’s CMV vaccine (mRNA-1647), the viral proteins in mRNA-1189 are expressed in their native membrane-bound form for recognition by the immune system. Moderna is planning to begin a Phase 1 study of mRNA-1189 in 2021. There is no approved vaccine for EBV. Moderna owns worldwide commercial rights to mRNA-1189.
Vaccines against respiratory infections

Human metapneumovirus (hMPV) and parainfluenza type 3 (PIV3) vaccine (mRNA-1653): Moderna is enrolling seropositive pediatric participants (12-36 months of age) in the Phase 1 study of hMPV/PIV3 study (mRNA-1653). The first cohort in this study has been fully enrolled. Moderna owns worldwide commercial rights to mRNA-1653.

Respiratory syncytial virus (RSV) vaccine (mRNA-1345): mRNA-1345 is a vaccine against RSV encoding for a prefusion F glycoprotein, which elicits a superior neutralizing antibody response compared to the postfusion state. RSV is the leading cause of respiratory illness in young children. Older adults (65+) are at high risk for severe RSV infections. mRNA-1345 uses the same lipid nanoparticle (LNP) as Moderna’s authorized COVID-19 vaccine and contains optimized protein and codon sequences. The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, older adults and children is ongoing. All four cohorts of younger adults (ages 18-49 years) are fully enrolled. Dosing in the older adult cohort (ages 65-79 years) is ongoing. The age range of toddlers in this de-escalation Phase 1 study is 12-59 months. The Company shared the first interim analysis of the Phase 1 study of mRNA-1345, through 1-month post-vaccination, of the younger adult cohorts at its annual Vaccines Dayon April 14, 2021. The Company also intends to evaluate the potential of combinations of mRNA-1345 with its vaccines against other respiratory pathogens in children and separately in older adults. There is no approved vaccine for RSV. Moderna owns worldwide commercial rights to mRNA-1345.
Seasonal influenza vaccine (mRNA-1010, mRNA-1020, mRNA-1030): Seasonal flu (type A and type B) epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing substantial burden on healthcare systems. The World Health Organization (WHO) estimates approximately 3-5 million severe cases of flu each year globally, and 290,000-650,000 flu-related respiratory deaths. Approximately 8% of the U.S. population experiences symptoms from flu each year. In the U.S., the estimated average economic burden of flu is approximately $11 billion per year. Current flu vaccines are only approximately 40-60% effective and their formulation is decided 9 months before the vaccines are intended to be used. Egg-based vaccine production also has the potential to cause unintended antigenic change to the vaccine virus. The Company plans to explore potential combination vaccines against flu, SARS-CoV-2, RSV and human metapneumovirus (hMPV). The Company’s first-generation flu program will evaluate multiple candidates comprising multiple antigen combinations against the four seasonal viruses recommended by the WHO. The Company expects to begin a Phase 1 clinical trial for the program in 2021.
Public health vaccines

Zika virus vaccine (mRNA-1893):Moderna is preparing for a Phase 2 study of mRNA-1893, which is expected to begin in 2021. mRNA-1893 is being developed in collaboration with BARDA. Moderna owns worldwide commercial rights to mRNA-1893.

HIV vaccine (mRNA-1644 & mRNA-1574): HIV is the virus responsible for acquired immunodeficiency syndrome (AIDS), a lifelong, progressive illness with no effective cure. Approximately 38 million people worldwide are currently living with HIV with 1.2 million in the U.S. Approximately 2 million new infections of HIV are acquired worldwide every year and approximately 690,000 people die annually due to complications from HIV/AIDS. The primary routes of transmission are sexual intercourse and IV drug use, putting young adults at the highest risk of infection. From 2000 to 2015, a total of $562.6 billion globally was spent on care, treatment and prevention of HIV, representing a significant economic burden. mRNA-1644, a collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation, is a novel approach to HIV vaccine strategy in humans designed to elicit broadly Neutralizing HIV-1 Antibodies (bNAbs). A Phase 1 study for mRNA-1644 will use iterative human testing to validate the approach and antigens and multiple novel antigens will be used for germline-targeting and immuno-focusing. A second approach, mRNA-1574, is being evaluated in collaboration with the NIH and includes multiple native-like trimer antigens. The Company expects to begin Phase 1 studies for both mRNA-1644 and mRNA-1574 in 2021.

Nipah virus (NiV) Vaccine (mRNA-1215): NiV is a zoonotic virus transmitted to humans from animals, contaminated food, or through direct human-to-human transmission and causes a range of illnesses including fatal encephalitis. Severe respiratory and neurologic complications of NiV have no treatment other than intensive supportive care. The case fatality rate among those infected is estimated at 40-75%. NiV outbreaks cause significant economic burden to impacted regions due to loss of human life and interventions to prevent further spread, such as the slaughter of infected animals. NiV has been identified as the cause of isolated outbreaks in India, Bangladesh, Malaysia, and Singapore since 2000 and is included on the WHO R&D Blueprint list of epidemic threats needing urgent R&D action. mRNA-1215 was co-developed by Moderna and the NIH’s Vaccine Research Center (VRC).
Pandemic influenza/H7N9 vaccine (mRNA-1851): Discussions regarding funding the Company’s pandemic influenza/H7N9 vaccine program through approval are ongoing.

Systemic Secreted & Cell Surface Therapeutics: In this modality, mRNA is delivered systemically to create proteins that are either secreted or expressed on the cell surface.

Antibody against the chikungunya virus (mRNA-1944): Positive interim data from the Phase 1 study evaluating escalating doses of mRNA-1944 in the 0.6 mg/kg dose with steroid premedication cohort and two doses of 0.3 mg/kg (without steroid premedication) given one week apart cohort were presented at Moderna’s annual R&D Day in September and demonstrated dose-dependent increases in levels of antibody against chikungunya. Safety and increased CHKV-IgG production in the two-dose regimen shows the platform’s ability for repeat dosing.

IL-2 (mRNA-6231): mRNA-6231 is an mRNA encoding for a long-acting tolerizing IL-2. This autoimmune development candidate is designed to preferentially activate and expand the regulatory T cell population. The Company plans to conduct a Phase 1 study of mRNA-6231 in healthy adult volunteers. mRNA-6231 uses the same LNP formulation as mRNA-1944. The Phase 1 study of mRNA-6231 will be the first clinical demonstration of subcutaneous administration of this delivery technology. Moderna owns worldwide commercial rights to mRNA-6231.

PD-L1 (mRNA-6981): mRNA-6981 is an mRNA encoding for PD-L1. This autoimmune development candidate is designed to augment cell surface expression of PD-L1 on myeloid cells to provide co-inhibitory signals to self-reactive lymphocytes. As an initial step to addressing a range of autoimmune indications, the Company intends to pursue proof-of-concept in a Phase 1 study of mRNA-6981 in type 1 autoimmune hepatitis (AIH), a condition that involves liver inflammation and can lead to cirrhosis and liver failure. mRNA-6981 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-6981.

Relaxin (AZD7970): Moderna has regained all rights to the Relaxin development candidate from AstraZeneca. Moderna now owns worldwide commercial rights to this development candidate.

Exploratory Modalities

Cancer Vaccines: These programs focus on stimulating a patient’s immune system with antigens derived from tumor-specific mutations to enable the immune system to elicit a more effective anti-tumor response.

Personalized cancer vaccine (PCV) (mRNA-4157): The randomized Phase 2 study investigating a 1 mg dose of mRNA-4157 in combination with Merck’s pembrolizumab (KEYTRUDA), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma is ongoing. Phase 1 in multiple cohorts is ongoing. The upsized head & neck cohort is recruiting additional patients. Moderna shares worldwide commercial rights to mRNA-4157 with Merck.

Mutant KRAS vaccine (mRNA-5671 or V941): The Phase 1 open-label, multi-center study to evaluate the safety and tolerability of mRNA-5671 both as a monotherapy and in combination with pembrolizumab, led by Merck, is ongoing. Moderna shares worldwide commercial rights to mRNA-5671 with Merck.

Intratumoral Immuno-Oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): The Phase 1/2 study of mRNA-2416 alone and in combination with durvalumab (IMFINZI) is ongoing. The Phase 2 dose expansion study of mRNA-2416 in combination with durvalumab in ovarian cancer patients is enrolling and the first patients have been dosed. Moderna owns worldwide commercial rights to mRNA-2416.
OX40L/IL-23/IL-36γ (Triplet) (mRNA-2752): The Phase 1 trial evaluating mRNA-2752 as a single agent and in combination with durvalumab in patients with advanced solid tumor malignancies and lymphoma is ongoing. mRNA-2752 is an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators. Moderna owns worldwide commercial rights to mRNA-2752.

IL-12 (MEDI1191): The Phase 1 open-label, multi-center study of intratumoral injections of MEDI1191 alone and in combination with durvalumab in patients with advanced solid tumors, led by AstraZeneca, is ongoing. MEDI1191 is an mRNA encoding for IL-12, a potent immunomodulatory cytokine. Moderna shares worldwide commercial rights to MEDI1191 with AstraZeneca.
Localized Regenerative Therapeutics: Localized production of proteins has the potential to be used as a regenerative medicine for damaged tissues.

VEGF-A (AZD8601): The Phase 2a study of AZD8601 VEGF-A, which is being developed for patients with ischemic heart disease undergoing coronary artery bypass grafting (CABG) surgery with moderately impaired systolic function, led by AstraZeneca, is ongoing. Moderna has licensed worldwide commercial rights to AZD8601 to AstraZeneca.

Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Propionic acidemia (PA) (mRNA-3927): The first patient in the Phase 1/2 Paramount studyof mRNA-3927 has been dosed. mRNA-3927 uses the same LNP formulation as mRNA-1944. This is the Company’s first development candidate in its systemic intracellular therapeutics modality to enter the clinic. Moderna owns worldwide commercial rights to mRNA-3927.

Methylmalonic acidemia (MMA) (mRNA-3705): Moderna received rare pediatric designation for its next generation MMA candidate (mRNA-3705). The Company plans to file new IND and CTA applications for mRNA-3705 and will focus development efforts on that candidate going forward. mRNA-3705 uses the same LNP formulation as mRNA-1944. Moderna owns worldwide commercial rights to mRNA-3705.

Phenylketonuria (PKU) (mRNA-3283): Individuals with PKU have a deficiency in phenylalanine hydroxylase (PAH) resulting in a reduced or complete inability to metabolize the essential amino acid phenylalanine into tyrosine. mRNA-3283 encodes human PAH to restore the deficient or defective intracellular enzyme activity in patients with PKU. mRNA-3283 is in preclinical development. Moderna owns worldwide commercial rights to mRNA-3283.
Glycogen storage disease type 1a (GSD1a) (mRNA-3745): Individuals with GSD1a have a deficiency in glucose-6-phosphatase resulting in pathological blood glucose imbalance. mRNA-3745 is an IV-administered mRNA encoding human G6Pase enzyme, designed to restore the deficient or defective intracellular enzyme activity in patients with GSD1a. mRNA-3745 is in preclinical development. Moderna owns worldwide commercial rights to mRNA-3745.
Information about each development candidate in Moderna’s pipeline can be found on the investor relations page of its website: investors.modernatx.com.

First Quarter 2021 Financial Results

Revenue: Total revenue was $1.9 billion for the three months ended March 31, 2021 compared to $8 million for the same period in 2020. Total revenue increased in the first quarter of 2021, resulting from a full quarter of commercial sales of the Company’s COVID-19 vaccine in the U.S. and an initial ramp up of international sales. A total of 102 million doses were recognized as revenue. Product sales were $1.7 billion for the three months ended March 31, 2021 from sales of the Company’s COVID-19 vaccine. The increase in grant revenue of $190 million was primarily driven by an increase in revenue from BARDA related to the Company’s COVID-19 vaccine development.

Cost of Sales: Costs of sales were $193 million, or 11%, of product sales the three months ended March 31, 2021, including third-party royalties of $84 million. A portion of the inventory costs associated with the Company’s products sales for the three months ended March 31, 2021 was expensed as pre-launch inventory costs in 2020. If inventory sold in the three months ended March 31, 2021 was valued at cost, the Company’s cost of sales for the quarter would have been $377 million, or 22% of product sales.

Research and Development Expenses: Research and development expenses were $401 million for the three months ended March 31, 2021 compared to $115 million for the same period in 2020. The growth in spending was mainly due to increases in clinical trial expenses, manufacturing expenses, personnel related costs, and consulting and outside services, largely driven by mRNA-1273 clinical development and increased headcount.

Selling, General and Administrative Expenses: Selling, general and administrative expenses were $77 million for the three months ended March 31, 2021 compared to $24 million for the same period in 2020. The growth in spending was mainly due to increases in consulting and outside services, personnel-related costs, legal and other licensing expenses, and marketing and other expenses, primarily attributable to increased headcount and the Company’s COVID-19 vaccine commercialization-related activities.

Net Income (Loss): Net income was $1.2 billion for the three months ended March 31, 2021 compared to a net loss of $(124) million for the same period in 2020.
Cash Position: Cash, cash equivalents and investments as of March 31, 2021 and December 31, 2020 were $8.2 billion and $5.2 billion, respectively.

Net Cash Provided by (Used in) Operating Activities: Net cash provided by operating activities was $3.0 billion for the three months ended March 31, 2021 compared to $(106) million used in operating activities for the same period in 2020. Net cash provided by operating activities increased significantly in 2021, mainly due to net income of $1.2 billion and additional customer deposits received in the first quarter for supply of the Company’s COVID-19 vaccine.

Cash Used for Purchases of Property and Equipment: Cash used for purchases of property and equipment was $35 million for the three months ended March 31, 2021 compared to $6 million for the same period in 2020.
2021 Updated Financial Framework

Advance Purchase Agreements (APAs): The Company has already signed APAs for scheduled delivery in 2021, for a total of $19.2 billion in anticipated product sales, including sales already recorded in the three months ended March 31, 2021.
Q2 Delivered Doses: The Company expects doses delivered in the second quarter 2021 to be in the range of 200-250 million doses.
Cost of Sales: Cost of sales as percentage of product sales are expected to be approximately 20% for fiscal year 2021.
2021 Research & Development (R&D) and Selling, General & Administrative (SG&A) Expenses: Expect quarter over quarter cost increases in R&D and SG&A expenses during 2021 as commercial and research and development activities and expenses ramp up.
Tax Rate: Effective tax rate expected in the low-teens as a result of the forecasted global sales mix and utilization of the accumulated net operating loss carry-forward of $2.3 billion, based on current tax rates.
Capital Expenditures: $450-550 million of capital investments currently planned for 2021 including the planned capacity expansion.

2022 and 2023 Vaccine Access Discussions

The Company has already signed APAs with Israel and Switzerland for 2022, and Switzerland has options for further deliveries in 2023. Through its recent agreement with COVAX, the Company has committed up to 466 million doses to COVAX for 2022. The Company is having ongoing discussions for 2022 APAs with all governments that have 2021 APAs. The Company is also having ongoing discussions to supply new geographies in Asia, Latin America and Africa in 2022 that it could not supply in 2021 due to manufacturing supply constraints. In response to feedback from governments for their desire to procure more high efficacy mRNA vaccines, the Company recently announced manufacturing investments to facilitate supply of up to 3 billion doses in 2022. The Company is also engaged in discussions with some governments for supply in 2023.

Management Updates

Shannon Thyme Klinger will join the Company as Chief Legal Officer and Corporate Secretary, effective June 1, 2021. Ms. Klinger joins Moderna from Novartis (NYSE: NVS), where she served as Chief Legal Officer and a member of the Novartis Executive Committee since 2018. Previously, she served as Chief Ethics, Risk & Compliance Officer. During her ten-year tenure at Novartis, she held other roles of increasing responsibility, including as Chief Ethics and Compliance Officer and Global Head of Litigation, General Counsel and Global Head of Legal at Sandoz, a Novartis division.
Corporate Updates

Full-Time Employees: Over the last year, the Company nearly doubled the size of its workforce. As of March 31, 2021, Moderna had approximately 1,500 employees, compared to approximately 830 employees as of March 31, 2020.
Vaccines Day: Moderna hosted its annual Vaccines Day on April 14, 2021.
Corporate Social Responsibility (CSR): Moderna CEO Stéphane Bancel published a letter on the Company’s commitment to CSR on April 27, 2021.
Company Recognition: Moderna was named as a top company on Fast Company’s annual list of the World’s Most Innovative Companies for 2021 and was named to TIME’s inaugural list of the TIME100 Most Influential Companies.

Key 2021 Investor and Analyst Event Dates

Science Day – May 27
R&D Day – September 9
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on Thursday, May 5, 2021. To access the live conference call, please dial 866-922-5184 (domestic) or 409-937-8950 (international) and refer to conference ID 7487119. A webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

On May 6, 2021 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported that it has entered into a clinical trial collaboration with a subsidiary of Merck (known as MSD outside the U.S. and Canada) to evaluate Fusion’s lead candidate, [225Ac]-FPI-1434 (FPI-1434), in combination with Merck’s anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA (pembrolizumab), in patients with solid tumors expressing insulin-like growth factor 1 receptor (IGF-1R) (Press release, Fusion Pharmaceuticals, MAY 6, 2021, View Source [SID1234579413]).

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"With our strong preclinical data demonstrating promising activity with FPI-1434 and immuno-oncology agents, we believe we have an opportunity to improve efficacy in tumor indications where KEYTRUDA is approved, and to potentially expand into new tumor indications," said Chief Executive Officer John Valliant, Ph.D. "This collaboration with Merck builds off our research on the mechanism of action of alpha radiation and aligns with our goal to expand the utility of radiopharmaceutical therapies, including advancing into earlier lines of cancer therapy."

The planned Phase 1/2 combination trial will evaluate safety, tolerability and pharmacokinetics of FPI-1434 in combination with pembrolizumab and is expected to initiate approximately six to nine months after achieving the recommended Phase 2 dose in the ongoing Phase 1 study of FPI-1434 monotherapy. Under the terms of the agreement, Fusion will sponsor the study and Merck will supply KEYTRUDA.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About FPI-1434
FPI-1434 is a radioimmunoconjugate designed to target and deliver alpha emitting medical isotopes to cancer cells expressing IGF-1R, a receptor that is overexpressed on many tumor types. FPI-1434 utilizes Fusion’s Fast-Clear linker to connect a human monoclonal antibody that targets IGF-1R with actinium-225, a powerful alpha-emitting isotope with desirable half-life and decay chain properties.