On February 25, 2021 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2020, and provided a corporate update (Press release, BioCryst Pharmaceuticals, FEB 25, 2021, View Source [SID1234575596]).

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"With two approvals for ORLADEYO, our launch in the U.S., proof of concept data for BCX9930 in complement-mediated diseases, a successful phase 1 trial of BCX9250 for FOP and the addition of more than $425 million through our May and December financings, 2020 was a transformational year for BioCryst," said Jon Stonehouse, president and chief executive officer of BioCryst.

"Using our strong balance sheet as a foundation, we expect to continue this transformation in 2021 with ORLADEYO generating revenue in the U.S., Japan and Europe, and the opportunity to significantly advance the 9930 program as an oral monotherapy for both PNH, and renal complement-mediated diseases," Stonehouse added.

Program Updates and Key Milestones

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

BioCryst launched ORLADEYO in the United States following U.S. Food and Drug Administration (FDA) approval on December 3, 2020, and product shipments began on December 16, 2020.

On January 22, 2021, the company announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan had granted marketing and manufacturing approval for oral, once-daily ORLADEYO 150 mg for prophylactic treatment of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

ORLADEYO is the first and only prophylactic HAE medication approved in Japan and will be commercialized in Japan by BioCryst’s partner, Torii Pharmaceutical Co., Ltd. OrphanPacific, Inc. is BioCryst’s representative partner in Japan and holds the marketing authorization.

Torii will launch ORLADEYO in Japan following the successful completion of BioCryst’s pricing negotiations with the Japanese National Health Insurance System (NHI).

BioCryst is eligible to receive an additional milestone payment of $15 million from Torii upon receipt of a reimbursement price from the NHI in excess of the threshold specified in the agreement with Torii. In addition, BioCryst will receive tiered royalties ranging from 20 percent to potentially 40 percent of Japanese net sales.
In Europe, the Committee for Medicinal Products for Human Use (CHMP) is scheduled to review the ORLADEYO marketing authorization application this week. The company expects approval from the European Commission (EC) approximately 60 days following a positive opinion from the CHMP.

On October 30, 2020, the company announced that the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) had granted ORLADEYO a positive scientific opinion through the Early Access to Medicines Scheme (EAMS). Under the EAMS, HAE patients in the UK aged 12 years and older can gain access to ORLADEYO for the routine prevention of recurrent attacks of HAE before the drug is granted marketing authorization by the EC.

In the fourth quarter of 2020, the company presented data in several manuscripts and abstracts.

On October 22, 2020, the company announced that data from the first 24 weeks of the Phase 3 APeX-2 trial of ORLADEYO in 121 HAE patients ages 12 years or older had been published online by the Journal of Allergy and Clinical Immunology.

On November 13, 2020, the company presented data in several abstracts at the 2020 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology across HAE patients, caregivers and treating physicians showing many patients experience a significant treatment burden associated with current prophylactic HAE therapies.

On November 30, 2020, the company announced that the journal Allergy had published data from the APeX-J trial, a randomized, placebo-controlled trial conducted in Japan evaluating ORLADEYO for the prophylactic treatment of HAE.
Complement Oral Factor D Inhibitor Program – BCX9930

The company has completed the enrollment of its ongoing dose ranging trial in treatment-naïve (no prior treatment with C5 inhibitors) paroxysmal nocturnal hemoglobinuria (PNH) patients, and PNH patients with an inadequate response to C5 inhibitors. The company plans to present data from the 16 enrolled PNH patients (10 treatment naïve and six inadequate C5 responders) at its upcoming R&D day on March 22.

In previously reported data from treatment-naïve (no prior treatment with C5 inhibitors) PNH patients receiving doses of oral BCX9930 through 400 mg bid, oral BCX9930 drove rapid and dose-dependent reductions in key biomarkers, including LDH, and increasing hemoglobin levels in all PNH patients in the trial. Increases in hemoglobin levels were maintained without transfusions. BCX9930 has been safe and well tolerated at all doses in the trial. No drug-related serious adverse events have been reported.
Additional Updates

On December 7, 2020, the company announced transactions totaling $325 million in funding for BioCryst, with $250 million available at closing, to support the launch of ORLADEYO in HAE and the development of BCX9930. Royalty Pharma provided BioCryst with an upfront cash payment of $125 million and will receive royalties on direct annual net sales of ORLADEYO up to $550 million, and a tiered percentage of sublicense revenue for ORLADEYO in certain territories. In addition, Royalty Pharma will receive a 1.0% royalty on global net sales of BCX9930, if approved. A fund managed by Athyrium Capital Management provided BioCryst with a $200 million credit facility, of which BioCryst drew $125 million at closing. The additional capital will be available in two tranches at BioCryst’s option, upon reaching defined revenue milestones. The credit facility bears interest at LIBOR + 8.25% (with a LIBOR floor of 1.75%) and is interest-only for the entire five-year term, with all outstanding principal due at maturity.

On December 21, 2020, the company announced that in a Phase 1 clinical trial with BCX9250, an oral activin receptor-like kinase-2 (ALK-2) inhibitor discovered and developed by BioCryst for the treatment of fibrodysplasia ossificans progressiva, BCX9250 was safe and well tolerated at all doses studied, with linear and dose-proportional exposure supporting once-daily dosing.

On February 3, 2021, the company announced that the FDA had approved a supplemental new drug application for RAPIVAB (peramivir injection) expanding the patient population of RAPIVAB for the treatment of acute uncomplicated influenza to include patients six months and older who have been symptomatic for no more than two days. Prior to this approval, RAPIVAB had been indicated for patients two years and older.
Fourth Quarter 2020 Financial Results

For the three months ended December 31, 2020, total revenues were $4.0 million, compared to $39.7 million in the fourth quarter of 2019. In the fourth quarter of 2019, we recognized revenue of $20.1 related to a one-time upfront milestone per the Torii agreement. Additionally, in that period we recognized $13.9 million of RAPIVAB product sales under our U.S. Department of Health and Human Services (HHS) contract, while in the fourth quarter 2020 we had no RAPIVAB product sales under our HHS contract. ORLADEYO revenues in the fourth quarter of 2020 were $0.1 million.

Research and development (R&D) expenses for the fourth quarter of 2020 increased to $35.4 million from $26.8 million in the fourth quarter of 2019, primarily due to increased investment in our Factor D and galidesivir programs, partially offset by a ramp down of clinical investment related to ORLADEYO, which launched commercially in the U.S. during December 2020.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2020 increased to $21.0 million, compared to $10.5 million in the fourth quarter of 2019. The increase was primarily due to increased investment in commercial activities to support the U.S. launch of ORLADEYO.

Interest expense was $5.6 million in the fourth quarter of 2020, compared to $3.1 million in the fourth quarter of 2019. This increase was due to service on the royalty and debt financings which were completed in December 2020. As part of those financings, there was also a loss on debt extinguishing related to the closing of our secured credit facility with MidCap Financial.

Net loss for the fourth quarter of 2020 was $60.5 million, or $0.34 per share, compared to a net loss of $2.6 million, or $0.02 per share, for the fourth quarter of 2019.

Cash, cash equivalents, restricted cash and investments totaled $302.6 million at December 31, 2020, and reflect an increase from $137.8 million at December 31, 2019. Cash, cash equivalents, restricted cash and investments include $250 million in cash received through transactions with Royalty Pharma and Athyrium Capital Management in December 2020. Operating cash use for the fourth quarter of 2020 was $49.9 million, and for the full year of 2020 was $147.9 million.

Full Year 2020 Financial Results

For the full year ended December 31, 2020, total revenues were $17.8 million, compared to $48.8 million in the full year ended December 31, 2019. In the fourth quarter of 2019 we recognized revenue of $20.1 related to a one-time upfront milestone per the Torii agreement, with the remaining amount of $1.9 million recognized in 2020. Additionally, in the fourth quarter of 2019 we recognized $13.9 million of RAPIVAB product sales under our HHS contract, while in the fourth quarter 2020 we had no RAPIVAB product sales under our HHS contract.

R&D expenses in full year 2020 increased to $123.0 million from $107.1 million in full year 2019, primarily due to increased investment in our Factor D and galidesivir programs, and an increase in other research, preclinical and development activities, partially offset by a ramp down of clinical investment related to ORLADEYO, which launched commercially in the U.S. during December 2020.

SG&A expenses in full year 2020 increased to $67.9 million, compared to $37.1 million in full year 2019. The increase was primarily due to increased investment in commercial activities to support the U.S. launch of ORLADEYO.

Interest and other income was $9.4 million in full year 2020, compared to $1.9 million in full year 2019. The increase was primarily due to the settlement of arbitration proceedings related to our Seqirus dispute in the first quarter of 2020.

Interest expense was $14.5 million in full year 2020, compared to $11.9 million in full year 2019. This was due to service on the royalty and debt financings which were completed in December 2020. As part of those financings, there was also a loss on debt extinguishing related to the closing of our secured credit facility with MidCap Financial.

Net loss for full year 2020 was $182.8 million, or $1.09 per share, compared to a net loss of $108.9 million, or $0.94 per share, for full year 2019.

Financial Outlook for 2021

In the launch period for ORLADEYO, the company is not providing specific revenue or operating expense guidance. Based on our expectations for revenue, operating expenses, and our option to access an additional $75 million from our existing credit facility, we believe our current cash runway takes us into 2023.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 6779206. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 6779206.

On February 25, 2021 Cerus Corporation (Nasdaq: CERS) reported financial results for the fourth quarter and year ended December 31, 2020 (Press release, Cerus, FEB 25, 2021, View Source [SID1234575634]).

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Recent developments and highlights include:

Record total fourth quarter and full year 2020 revenues of $33.6 million and $114.2 million, respectively. Total revenue was composed of (in millions, except %):

Provided 2021 annual product revenue guidance of $106 million to $110 million, representing an approximately 15% to 20% increase over 2020 reported product revenue.
Received FDA approval for the INTERCEPT Blood System for Cryoprecipitation, which can now be used to produce two products: Pathogen Reduced Cryoprecipitated Fibrinogen Complex (PR-Cryo FC) for the treatment and control of bleeding, including massive hemorrhage, associated with fibrinogen deficiency, and a derivative product, called Pathogen Reduced Plasma, Cryoprecipitate Reduced.
Announced the formation of a joint venture with Shandong Zhongbaokang Medical Implements that intends to develop, register, manufacture and commercialize the INTERCEPT Blood System for platelets and red blood cells in China.
Announced Brazilian distribution partner, CEI, was awarded a three-year tender award for the INTERCEPT Blood System for platelets with the HemoMinas Foundation of Brazil.
Ended 2020 with cash, cash equivalents, and short-term investments of $133.6 million at December 31, 2020.
"The COVID-19 pandemic has fundamentally altered the way the world thinks about pandemic preparedness. As we recognize a record quarter and year for our business, there remains much work to do with blood centers and hospitals around the world to ensure the safety and availability of the blood supply and protect patients from infectious viral diseases and bacterial contaminants. During a year unlike any other, I am proud of the significant commercial momentum we generated in 2020 to help advance pathogen reduced blood products towards the standard of care in transfusion medicine," said William ‘Obi’ Greenman, Cerus’ president and chief executive officer. "With customers continuing to increase production of INTERCEPT platelets, we are poised for another year of solid top-line growth in 2021. Additionally, our team is working to launch our recently FDA approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex product and to advance our pipeline programs. While we have made tremendous progress, we still have much work to do to realize our mission to safeguard the global blood supply. We look forward to updating our stakeholders as we make progress towards our key milestones over the course of the year."

Revenue

Product revenue during the fourth quarter of 2020 was $28.2 million, compared to $20.9 million during the same period in 2019. Product revenue growth in the quarter benefited from strong continued demand for INTERCEPT platelet kits in the U.S., continued growth in platelet kit demand in EMEA, and strong illuminator sales. For the full year, product revenue totaled $91.9 million, an increase of 23% compared to the same period in 2019.

Although the Company generally had more activity during 2020 for its INTERCEPT red blood cell system covered through its contract with the Biomedical Advanced Research and Development Authority (BARDA), there were a number of COVID-19 related delays and disruptions to clinical activities. Accordingly, government contract revenue primarily from the BARDA agreement was $5.4 million during the fourth quarter of 2020, compared to $5.6 million during the same period in 2019. Full year 2020 government contract revenue totaled $22.3 million compared to $19.1 million in the same period of the year prior. The total potential value of the current BARDA agreement is $214 million, with $66.4 million cumulatively recognized as government contract revenue through December 31, 2020.

BARDA is part of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services. The development of the INTERCEPT red blood cell program has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201600009C.

Gross Margins

Gross margins on product revenue during the fourth quarter of 2020 were 56.8% compared to 55.6% for the fourth quarter of 2019. The increase in gross margin was tied to increased volumes of INTERCEPT kits sold, driving economies of scale within our production cycle, and favorable foreign exchange rates with a weakening U.S. dollar relative to the Euro. Gross margins on product revenue for the full year 2020 and 2019 were 55.2%.

Operating Expenses

Total operating expenses for the fourth quarter of 2020 were $35.8 million compared to $33.6 million for the same period of the prior year. Full year 2020 operating expenses totaled $131.4 million compared to $126.6 million for the full-year 2019.

Selling, general, and administrative (SG&A) expenses for the fourth quarter of 2020 totaled $18.7 million, compared to $17.2 million for the fourth quarter of 2019. The year-over-year increase in SG&A expenses was tied to increased non-cash stock-based compensation, and investments ahead of the Company’s anticipated PR-Cryo FC launch. Full-year 2020 SG&A expenses totaled $67.0 million compared to $66.2 million for the full-year 2019.

Research and development (R&D) expenses for the fourth quarter of 2020 were $17.1 million, compared to $16.4 million for the fourth quarter of 2019. The year-over-year increase in R&D expenses was largely due to non-cash stock-based compensation and product enhancements and initiatives for expanded label claims. Full-year 2020 R&D expenses totaled $64.4 million compared to $60.4 million for the full-year 2019.

Net Loss

Net loss for the fourth quarter of 2020 was $14.4 million, or $0.09 per basic and diluted share, compared to a net loss of $16.9 million, or $0.12 per basic and diluted share, for the fourth quarter of 2019. Full-year 2020 net loss was $59.9 million, or $0.37 per basic and diluted share, compared to $71.2 million, or $0.51 per basic and diluted share, for the same period in 2019.

Balance Sheet

At December 31, 2020, the Company had cash, cash equivalents and short-term investments of $133.6 million, compared to $85.7 million at December 31, 2019.

At December 31, 2020, the Company had approximately $39.6 million in outstanding term loan debt and $8.5 million of borrowings under its revolving loan credit agreement, compared to $39.4 million in outstanding term loan debt and $5.0 million of borrowings under its revolving loan credit agreement at December 31, 2019.

2021 Product Revenue Guidance

The Company expects 2021 product revenue to be in the range of $106 million to $110 million. The guidance range represents approximately 15% to 20% growth compared to 2020 reported product revenue.

QUARTERLY CONFERENCE CALL

The Company will host a conference call at 4:30 P.M. EDT this afternoon, during which management will discuss the Company’s financial results and provide a general business overview and outlook. To listen to the live webcast, please visit the Investor Relations page of the Cerus website at View Source Alternatively, you may access the live conference call by dialing (866) 235-9006 (U.S.) or (631) 291-4549 (international).

A replay will be available on the Company’s website, or by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and entering conference ID number 1267389. The replay will be available approximately three hours after the call through March 11, 2021.

On February 25, 2021 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a clinical-stage biopharmaceutical company dedicated to the development of cellular therapies designed to reverse disease, reported financial results for the three and twelve months ended December 31, 2020 (Press release, Caladrius Biosciences, FEB 25, 2021, View Source [SID1234575662]).

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"Despite the continued headwinds of the global pandemic, we are pleased to report continued progress of our development programs as well as an improved financial situation during the fourth quarter and full year of 2020, which reflect the resiliency, creativity and strength of our team and the growing optimism associated with our CD34+ cell technology-based clinical programs," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius. "We ended 2020 in a strong financial and strategic position and have set the stage for key clinical enrollment milestones this year.

"Importantly, we have continued the operational momentum into 2021 with an even further strengthened balance sheet, giving us the confidence and means to expand program development and execute on our business priorities," Dr. Mazzo concluded.

Product Development and Financing Highlights

CLBS16 for the treatment of coronary microvascular dysfunction

Caladrius reported in May 2020 the compelling positive results of its ESCaPE-CMD Phase 2a study of CLBS16 for the treatment of coronary microvascular dysfunction ("CMD"), a disease that continues to be underdiagnosed and potentially afflicts millions annually – a vast majority of whom are female – with no current treatment options. The Company is committed to raising awareness of this growing women’s health crisis and finding an effective treatment for it. Consequently, Caladrius recently initiated a rigorous 105-subject Phase 2b clinical trial (the FREEDOM trial), which, to our knowledge, is the first controlled regenerative medicine trial in CMD, and, which is currently recruiting and treating patients and is targeted to complete enrollment by the end of 2021 with top line data anticipated for the third quarter of 2022. This double-blind, randomized, placebo-controlled Phase 2b trial will evaluate the efficacy and safety of delivering autologous CD34+ cells in subjects with CMD and without obstructive coronary artery disease. In support of the FREEDOM trial, the Company is engaging with the American Heart Association for a variety of initiatives around Heart Health Month (February) and the "Go Red for Women" campaign to help raise awareness of CMD.

HONEDRA (CLBS12) for the treatment of critical limb ischemia

The Company’s open-label, registration-eligible study of SAKIGAKE-designated HONEDRA in Japan for the treatment of critical limb ischemia ("CLI") and Buerger’s Disease (an orphan-sized subset of CLI) has shown strong results to date. The initial responses observed in the subjects who have reached an endpoint in this study are consistent with a therapeutic effect and safety profile reported by previously published clinical trials in Japan and the USA. Although the study’s enrollment has been slowed by the pandemic’s impact in Japan, the Company is encouraged by the patient pre-screening pipeline and hopes to conclude trial enrollment during the second quarter of 2021. While the final outcome of the trial will depend on all data from all subjects, the data to date is very encouraging (~60% of subjects in the completed Buerger’s Disease cohort have reached a positive "CLI-free" endpoint, despite a natural history of such patients predicting continuing disease progression to amputation).

CLBS201 for the treatment of pre-dialysis chronic kidney disease

Our most recently proposed development program, CLBS201, is designed to assess the safety and efficacy of CD34+ cell therapy as a treatment for chronic kidney disease ("CKD") in patients not yet requiring dialysis. Based on a wealth of published preclinical and early clinical data, it appears that the innate ability of CD34+ cells to promote the growth of new microvasculature could be a means to attenuate the progression of the disease or even reverse the course of CKD. Caladrius plans to file an IND for this program in the second quarter of 2021 and to initiate a Phase 1/2 proof-of-concept study of CLBS201 in a moderate to severe CKD population shortly thereafter. Chronic Kidney Disease remains a largely unmet medical need, especially as the general population ages and the incidence of diabetes and hypertension increases.

OLOGO for the treatment of no option refractory disabling angina ("NORDA")

We acquired the rights to data and regulatory filings for a CD34+ cell therapy program for NORDA that had been advanced to Phase 3 by a previous sponsor. Based on the clinical evidence from the completed studies that a single administration of OLOGO reduces mortality, improves angina and increases exercise capacity in patients with otherwise untreatable angina, this product received Regenerative Medicine Advanced Therapy ("RMAT") designation from the FDA. We remain in discussion with the FDA regarding the size and scope of a phase 3 trial which, in combination with previously filed Phase 1, 2 and 3 data, will be considered for the registration of OLOGO. Notably, the RMAT designation affords the product a 6-month review time for a biologics license application ("BLA"), once submitted.

Closed on an additional $90.0 million in funding

In January 2021, the Company announced that it had closed on a $25.0 million capital raise through the sale of its common stock to several institutional and accredited investors in a private placement priced at-the-market under Nasdaq rules. In February 2021, the Company announced that it closed a $65.0 million capital raise through the sale of its common stock to several institutional and accredited investors in two registered direct offerings priced at-the-market under Nasdaq rules.

Fourth Quarter and Full Year 2020 Financial Highlights

Research and development expenses for the fourth quarter of 2020 were $2.9 million, a 5% increase compared with $2.8 million for the fourth quarter of 2019, and $9.3 million for the year ended December 31, 2020 compared to $10.8 million for the year ended December 31, 2019, representing a decrease of approximately 14%. Research and development in both the current year and prior year periods focused on the advancement of our ischemic repair platform and related to:

Expenses associated with exploration of our concept program, CLBS119, a CD34+ cell therapy for repair of COVID-19 induced lung damage targeting patients with severe SARS-CoV-2 infection that required ventilatory support due to respiratory failure (this program has since been indefinitely postponed due to the continuous evolution of the targeted patient population);

Ongoing expenses for HONEDRA in critical limb ischemia in Japan, whereby we continue to focus spending on patient enrollment and Japanese NDA preparation (enrollment completion is now targeted for 2Q21 based on the impact of the COVID-19 pandemic in Japan);

Expenses associated with the proof-of-concept study for CLBS16 in coronary microvascular dysfunction, for which study enrollment was completed in the second quarter of 2019 and full results reported in May 2020 and continuing efforts to advance CLBS16 into a Phase 2b study (the FREEDOM trial) in the second half of 2020; and
Expenses associated with the ongoing dialogue with FDA regarding design and execution of confirmatory Phase 3 study of OLOGO in NORDA.
General and administrative expenses, which focus on general corporate related activities, were $2.5 million for the three months ended December 31, 2020, compared to $2.3 million for the three months ended December 31, 2019, and $9.9 million for the year ended December 31, 2020, compared to $9.3 million for the year ended December 31, 2019, representing an increase of 6%.

Overall, net losses were $8.1 million and $19.4 million for the years ended December 31, 2020 and 2019, respectively.

Balance Sheet Highlights

As of December 31, 2020, Caladrius had cash, cash equivalents and marketable securities of $34.6 million and, following the previously mentioned capital raises in January and February 2021, the Company has cash, cash equivalents and marketable securities of approximately $116 million as of February 25, 2021. Based on existing programs and projections, the Company remains confident that its current cash balances will fund its operations for the next several years, notably, through study completion for the Phase 2b for CLBS16, through the registration-eligible study completion for HONEDRA and through the Phase 1/2 Proof-of-Concept study for CLBS201 while still providing capital to explore additional pipeline expansion opportunities.

Conference Call

Caladrius will hold a conference call on Thursday, February 25, 2021, at 4:30 p.m. Eastern time to discuss the financial results, provide a business update and answer questions. To join the conference call, please refer to the dial-in information provided below. The conference call will also be webcast live under the Investors section on the Company’s website at www.caladrius.com.

For those unable to participate in the live conference call, an audio replay will be available approximately two hours after the call has concluded until March 4, 2021, by dialing 855-859-2056 (domestic) or 404-537-3406 (international) and referencing conference ID / passcode: 7372695. A webcast recording of the call will also be archived for 90 days under the Investors section of the Company’s website at www.caladrius.com.

On February 25, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2020 (Press release, Intellia Therapeutics, FEB 25, 2021, View Source [SID1234575597]).

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"Intellia’s achievements in 2020 reflect important progress on both our full-spectrum strategy and our mission to deliver curative genome editing treatments for people with severe diseases. Dosing our first patient with NTLA-2001, the first-ever systemically delivered CRISPR-based therapy, was a major milestone for our team, as we completed our transition to a clinical-stage company in the fourth quarter," said Intellia President and Chief Executive Officer, John Leonard, M.D. "Looking ahead, we are focused on our three core priorities for 2021: clinical validation of our approach with NTLA-2001, advancement and expansion of our in vivo and ex vivo pipeline, and continued platform innovation. We have made steady progress in our global Phase 1 study of NTLA-2001 and look forward to sharing our first clinical data this year. Additionally, we are on track to submit first-in-human regulatory applications to begin clinical studies of NTLA-5001 for AML and NTLA-2002 for HAE, and we plan to nominate at least one new development candidate from our research portfolio."

Fourth Quarter 2020 and Recent Operational Highlights

NTLA-2001 for ATTR: NTLA-2001 is the first systemically delivered CRISPR-based therapy dosed in a patient and could potentially be the first curative treatment for ATTR. By applying the Company’s in vivo lipid nanoparticle (LNP) delivery technology, NTLA-2001 offers the possibility of halting and reversing the disease with potent, lifelong transthyretin (TTR) protein reduction after a single course of treatment. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party, and Regeneron Pharmaceuticals, Inc. (Regeneron).

The Company anticipates reporting interim clinical data from the Phase 1 study this year. These results are expected to characterize the emerging safety and activity profile of NTLA-2001 at the initial dose levels.
In November, Intellia dosed the first patient in its global Phase 1 study evaluating NTLA-2001 in adults with hereditary ATTR with polyneuropathy (hATTR-PN). The Company continues to enroll patients in the study and is submitting additional regulatory applications in other countries as part of its ongoing, global development strategy.
Intellia intends to evaluate NTLA-2001 in a broader ATTR population of both polyneuropathy and cardiomyopathy patients following its Phase 1 safety assessment and dose optimization.
NTLA-5001 for AML: NTLA-5001 is a potential best-in-class engineered T cell therapy designed to treat all genetic subtypes of AML. This investigational candidate is an autologous T cell receptor (TCR)-T cell therapy targeting the Wilms’ Tumor 1 (WT1) antigen utilizing Intellia’s proprietary cell engineering process.

Intellia plans to submit an Investigational New Drug (IND) application or equivalent regulatory application for NTLA-5001 in mid-2021. This first-in-human trial is expected to evaluate the safety and activity of NTLA-5001 in patients with persistent or recurrent AML who have previously received first-line therapies.
NTLA-5001 shows high anti-tumor activity in proof-of-concept mouse models of acute leukemias. The preclinical data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December highlighted faster expansion and superior function of T cells manufactured by Intellia’s proprietary approach, compared to standard T cell engineering approaches currently in use.
The Company is also evaluating the potential use of NTLA-5001 to treat WT1-positive solid tumors in preclinical studies.
NTLA-2002 for HAE: NTLA-2002 aims to prevent attacks for people living with HAE after a single course of treatment. Intellia is applying its modular LNP delivery system to develop NTLA-2002 to knock out the KLKB1 gene in the liver to permanently reduce plasma kallikrein activity. This approach is expected to provide continuous suppression of kallikrein activity and eliminate the significant treatment burden associated with currently available therapies for HAE patients.

Intellia commenced clinical manufacturing activities to support the Company’s plans to submit an IND or equivalent regulatory application in the second half of 2021.
The Company is applying insights gained from NTLA-2001 to expedite clinical development of NTLA-2002. The first-in-human trial is expected to evaluate safety, tolerability and activity in patients with HAE.
The Company plans to present additional preclinical results in support of NTLA-2002 at the upcoming American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting, taking place virtually from February 26 – March 1, 2021.
Modular Platform and Pipeline Expansion: Intellia is advancing its modular platform technologies to broaden the in vivo and ex vivo applications of genome editing. This includes developing capabilities for innovative CRISPR/Cas9-mediated in vivo editing in multiple tissue types, targeted transgene insertion and an allogeneic approach for the development of "off-the-shelf" T cell therapies. These efforts will support new therapeutic candidates for genetic diseases requiring removal and/or restoration of a protein, and next-generation engineered cell therapies for cancers and auto-immune diseases.

Intellia plans to nominate at least one additional development candidate in 2021 and expects to present preclinical data at upcoming scientific conferences highlighting research advancements and platform innovations.
Intellia demonstrated the modularity of its targeted insertion approach for a second target, in non-human primates, showing insertion of the SERPINA1 gene produced normal levels of human alpha-1 antitrypsin (AAT) after a single administration. In December, these results were presented at the Alpha-1 Foundation’s 20th Gordon L. Snider Critical Issues Workshop: The Promise of Gene-Based Interventions of Alpha-1 Antitrypsin Deficiency. Intellia is advancing multiple genome editing strategies that may treat both lung and liver manifestations of AAT deficiency (AATD), which occur due to mutations in the SERPINA1 gene.
Intellia is advancing preclinical validation of in vivo hematopoietic stem cell (HSC) genome editing using the Company’s proprietary non-viral delivery systems and CRISPR/Cas9 technology to potentially cure sickle cell disease. This research is supported by a grant from the Bill & Melinda Gates Foundation.
Financing: In December, Intellia closed an underwritten public offering of 5,513,699 shares of common stock, including the exercise in full of the underwriters’ option to purchase additional shares, at the public offering price of $36.50 per share. Intellia received aggregate gross proceeds of approximately $201 million, before underwriting discounts and commissions and offering expenses.
Upcoming Events

The Company will participate in the following events during the first quarter of 2021:

AAAAI Annual Meeting, February 26–March 1, Virtual
Keystone Symposium: Precision Engineering of the Genome, Epigenome and Transcriptome, March 8-10, Virtual
Barclays Capital Global Healthcare Conference, March 8, Virtual
Oppenheimer’s 31st Annual Healthcare Conference, March 16, Virtual
Cold Spring Harbor Laboratories meeting on Nucleic Acid Therapies, March 24 – 26, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR: Report initial clinical data from Phase 1 study of NTLA-2001 in 2021
AML: Submit an IND or IND-equivalent for NTLA-5001 in mid-2021
HAE: Submit an IND or IND-equivalent for NTLA-2002 in 2H 2021
Nominate at least one new development candidate in 2021
Fourth Quarter and Full-Year 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $597.4 million as of December 31, 2020, compared to $284.5 million as of December 31, 2019. The increase was driven by net proceeds of $296.6 million from our follow-on public offerings, $100.0 million upfront payment from the Regeneron collaboration expansion, which included a $30.0 million equity investment, $49.5 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $18.2 million from the Regeneron and Novartis Institutes for BioMedical Research, Inc. (Novartis) collaborations and $13.2 million in proceeds from employee-based stock plans. These increases were offset in part by cash used to fund operations of approximately $164.6 million.
Collaboration Revenue: Collaboration revenue decreased by $4.3 million to $6.6 million during the fourth quarter of 2020, compared to $10.9 million during the fourth quarter of 2019. The decrease was primarily driven by a decrease in Novartis revenue as the research portion of the collaboration ended in December 2019.
R&D Expenses: Research and development expenses increased by $6.5 million to $38.2 million during the fourth quarter of 2020, compared to $31.7 million during the fourth quarter of 2019. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $1.8 million to $10.8 million during the fourth quarter of 2020, compared to $9.0 million during the fourth quarter of 2019. This increase was primarily related to employee related expenses, including stock-based compensation of $1.3 million.
Net Loss: The Company’s net loss was $42.2 million for the fourth quarter of 2020, compared to $28.3 million during the fourth quarter of 2019.
Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of December 31, 2020 will enable the Company to fund its robust R&D plans, anticipated operating expenses and capital expenditure requirements at least through the next 24 months. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Fourth Quarter and Full-Year 2020 Earnings

The Company will discuss these results on a conference call today, February 25, 2021, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call.
All participants should ask to be connected to the Intellia Therapeutics conference call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at www.intelliatx.com, beginning on February 25, 2021 at 12 p.m. ET.

On February 25, 2021 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the year ended December 31, 2020 (Press release, MacroGenics, FEB 25, 2021, View Source [SID1234575635]).

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"Following the approval in late 2020 of our first drug with the U.S. Food and Drug Administration (FDA), 2021 has the potential to be another transformative year for MacroGenics. We expect to launch MARGENZA in the coming weeks and will continue to advance our deep pipeline of promising product candidates in multiple clinical trials," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We are particularly excited about our ongoing, potentially registration-enabling studies, including flotetuzumab in acute myeloid leukemia (AML) and margetuximab in gastric cancer, as well as two Prescription Drug User Fee Act (PDUFA) target action dates in July related to retifanlimab and teplizumab. And finally, we look forward to providing clinical updates on multiple, ongoing dose expansion studies this year."

Key Updates on Proprietary Programs

Recent progress and anticipated events in 2021 related to MacroGenics’ approved and investigational product candidates in clinical development, as well as an advanced preclinical program, are highlighted below.

Margetuximab is an Fc-engineered, monoclonal antibody (mAb) that targets the HER2 oncoprotein, which is expressed by certain breast, gastroesophageal and other solid tumor cells.

MARGENZA (margetuximab-cmkb) approval and commercial launch. In December 2020, the FDA approved MARGENZA in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The launch, which is being coordinated with MacroGenics’ commercial partner, EVERSANA, is expected in March.
Phase 2/3 MAHOGANY study in advanced gastric (GC) and gastroesophageal junction (GEJ) cancer. The MAHOGANY clinical program contains two modules designed to evaluate margetuximab as an investigational agent in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment for patients with advanced or metastatic HER2-positive GC/GEJ. Initial safety and efficacy data from among the first 40 patients enrolled in Module A, which is evaluating margetuximab in combination with retifanlimab (an anti-PD-1 therapy), are expected in the first half of 2021. Enrollment in Module B, which is evaluating margetuximab plus MacroGenics’ checkpoint inhibitor molecules in combination with chemotherapy compared to standard of care therapy of trastuzumab with chemotherapy in patients with HER2-positive tumors irrespective of PD-L1 expression, is currently ongoing in coordination with the Company’s regional partner in Greater China, Zai Lab.
Flotetuzumab is a bispecific CD123 × CD3 DART molecule being evaluated in patients with primary induction failure (PIF) and early relapsed (less than six months, or ER6) AML. Six clinical and preclinical abstracts related to AML and flotetuzumab were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in December 2020. MacroGenics is conducting a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with PIF/ER6 AML, with complete remission (CR) and CR with partial hematological recovery (CRh) as the composite primary endpoint. The Company anticipates providing further updates on the clinical development of flotetuzumab in the second half of 2021, and completing full enrollment of this study in 2022.
MGC018 is an antibody-drug conjugate that targets B7-H3. MacroGenics continues to enroll patients with metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) in the dose expansion portion of the Phase 1 clinical study. The Company expects to provide an update on this study in mid-2021.
Enoblituzumab is an Fc‐engineered, anti‐B7‐H3 mAb. In the coming weeks, MacroGenics expects to initiate a Phase 2 study of enoblituzumab in a chemo-free regimen in combination with retifanlimab in front-line patients with squamous cell carcinoma of the head and neck (SCCHN) who are PD-L1 positive and with tebotelimab in SCCHN patients who are PD-L1 negative.
Tebotelimab is a bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types. An oral presentation of tebotelimab Phase 1 data in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) was made at ASH (Free ASH Whitepaper) in December 2020. In addition, data from the combination study of tebotelimab and margetuximab in patients with advanced HER2+ neoplasms were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2020. MacroGenics’ regional partner in Greater China, Zai Lab, is also evaluating tebotelimab in Phase 1 combination studies with niraparib and brivanib for the study of advanced gastric cancer and hepatocellular carcinoma, respectively, as well as a monotherapy study in patients with melanoma. MacroGenics expects to provide clinical updates on tebotelimab in 2021, including future development plans.
MGD019 is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. The Company is enrolling Phase 1 dose expansion cohorts, initially in patients with microsatellite stable colorectal cancer (MSS CRC) and checkpoint-naïve NSCLC at the recommended Phase 2 dose. The Company expects to provide a clinical update on this study in mid-2021.
IMGC936 is an antibody-drug conjugate that targets ADAM9, a cell surface protein over-expressed in several solid tumor types. IMGC936 is being advanced under a co-development agreement with ImmunoGen, Inc. Under the 50/50 collaboration, ImmunoGen is leading clinical development and the Phase 1 dose escalation study is currently enrolling patients with select advanced solid tumors.
MGD024 is a next-generation, bispecific CD123 × CD3 DART molecule in preclinical development. The molecule incorporates a CD3 component designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, along with an Fc domain to permit intermittent dosing through a longer half-life. The Company anticipates submitting an Investigational New Drug (IND) application to the FDA by the end of 2021.
Key Partnered Programs Update

Recent progress and disclosed priorities for MacroGenics’ partnerered investigational molecules are highlighted below.

Retifanlimab is an anti-PD-1 mAb that has been exclusively licensed to Incyte Corporation. To date, MacroGenics has earned $65 million in milestones related to retifanlimab, triggered by advancement of the molecule through various clinical and regulatory activities. In January 2021, Incyte announced that the FDA had accepted for Priority Review its Biologics License Application (BLA) for retifanlimab as a potential treatment for adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal. The PDUFA target action date for retifanlimab is July 25, 2021. MacroGenics is eligible to receive up to a total of $685 million in potential remaining development, regulatory and commercial milestones. If retifanlimab is approved and commercialized, MacroGenics would be eligible to receive royalties, tiered from 15 to 24 percent, on future worldwide net sales of the drug.
Teplizumab is a mAb being developed by Provention Bio, Inc. for the treatment of type 1 diabetes. In January 2021, Provention announced the FDA filing of a BLA and Priority Review for this molecule, with a PDUFA target action date of July 2, 2021. In 2018, MacroGenics sold its interest in teplizumab to Provention and is eligible to receive up to $170 million upon the achievement of certain regulatory approval milestones, including $60 million upon approval of a BLA in the U.S., additional milestone payments totaling $225 million upon the achievement of certain sales milestones and single-digit royalties on net sales of the molecule.
Corporate Updates

Janssen Collaboration. In December 2020, MacroGenics announced a research collaboration and global license agreement to develop a preclinical bispecific molecule with Janssen Biotech, Inc. The research collaboration will incorporate MacroGenics’ proprietary DART platform to enable simultaneous targeting of two undisclosed targets in a therapeutic area outside oncology. Under the terms of the agreement, Janssen paid MacroGenics an upfront payment of $20 million and will be responsible for funding all expenses. MacroGenics will also be eligible to receive up to $312 million in potential milestone payments and tiered royalties on worldwide product sales.
Ms. Federica O’Brien Added to Board. MacroGenics recently announced the appointment of Federica "Freddi" O’Brien, a veteran executive with 25 years of financial and operational leadership in biopharmaceutical, medical device, and technology companies, to its Board of Directors.
2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2020 were $272.5 million, compared to $215.8 million as of December 31, 2019.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $104.9 million for the year ended December 31, 2020, compared to $64.2 million for the year ended December 31, 2019. This increase was primarily due to the recognition of milestones, partially offset by timing of revenue recognition under the Company’s collaborative agreements.
R&D Expenses: Research and development expenses were $193.2 million for the year ended December 31, 2020, compared to $195.3 million for the year ended December 31, 2019.
G&A Expenses: General and administrative expenses were $42.7 million for the year ended December 31, 2020, compared to $46.1 million for the year ended December 31, 2019. This decrease was primarily due to a decrease in external costs, including consulting.
Net Loss: Net loss was $129.7 million for the year ended December 31, 2020, compared to net loss of $151.8 million for the year ended December 31, 2019.
Shares Outstanding: Shares outstanding as of December 31, 2020 were 56,244,771.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities as of December 31, 2020, as well as anticipated and potential collaboration payments, should enable it to fund its operations into 2023, assuming the Company’s programs and collaborations advance as currently contemplated.
Conference Call Information

MacroGenics will host a conference call today at 4:30 pm (ET) to discuss financial results for the year ended December 31, 2020 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 6094343.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

IMPORTANT SAFETY INFORMATION – MARGENZA
BOXED WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY

Left Ventricular Dysfunction: MARGENZA may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate cardiac function prior to and during treatment. Discontinue MARGENZA treatment for a confirmed clinically significant decrease in left ventricular function.
Embryo-Fetal Toxicity: Exposure to MARGENZA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
WARNINGS & PRECAUTIONS:

Left Ventricular Dysfunction

Left ventricular cardiac dysfunction can occur with MARGENZA.
MARGENZA has not been studied in patients with a pretreatment LVEF value of <50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.
Withhold MARGENZA for ≥16% absolute decrease in LVEF from pre-treatment values or LVEF below institutional limits of normal (or 50% if no limits available) and ≥10% absolute decrease in LVEF from pretreatment values.
Permanently discontinue MARGENZA if LVEF decline persists greater than 8 weeks, or dosing is interrupted more than 3 times due to LVEF decline.
Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment. Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan.
Monitor cardiac function every 4 weeks if MARGENZA is withheld for significant left ventricular cardiac dysfunction.
Embryo-Fetal Toxicity

Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. Post-marketing studies of other HER-2 directed antibodies during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.
Advise pregnant women and women of reproductive potential that exposure to MARGENZA during pregnancy or within 4 months prior to conception can result in fetal harm.
Advise women of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of MARGENZA.
Infusion-Related Reactions (IRRs)

MARGENZA can cause IRRs. Symptoms may include fever, chills, arthralgia, cough, dizziness, fatigue, nausea, vomiting, headache, diaphoresis, tachycardia, hypotension, pruritus, rash, urticaria, and dyspnea.
Monitor patients during and after MARGENZA infusion. Have medications and emergency equipment to treat IRRs available for immediate use.
In patients experiencing mild or moderate IRRs, decrease rate of infusion and consider premedications, including antihistamines, corticosteroids, and antipyretics. Monitor patients until symptoms completely resolve.
Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension and intervene with supportive medical therapy as needed. Permanently discontinue MARGENZA in all patients with severe or life-threatening IRRs.
MOST COMMON ADVERSE REACTIONS:

The most common adverse drug reactions (≥10%) with MARGENZA in combination with chemotherapy are fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain.