On February 24, 2022 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported financial results for the fourth quarter and full-year periods ended December 31, 2021 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, FEB 24, 2022, View Source [SID1234608990]).

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"2021 was another year of strong execution for SpringWorks as we advanced our targeted oncology portfolio and continued to build a fully-integrated biopharmaceutical company with capabilities spanning research, early and late-stage development, and commercial," said Saqib Islam, Chief Executive Officer of SpringWorks. "2022 is set up to be a meaningful year for us and the patients we are working to serve as we expect to share data across our pipeline, including topline data from the Phase 3 DeFi study and clinical data across our BCMA and biomarker-defined metastatic solid tumor programs. We believe we have a strong infrastructure that will allow us to continue to build upon the multiple opportunities we have created and drive our growth in 2022 and beyond."

Recent Business Highlights and Upcoming Milestones

Rare Oncology

SpringWorks is conducting the Phase 3 DeFi trial evaluating nirogacestat in adult patients with progressing desmoid tumors. DeFi is an event-driven trial with a primary endpoint of progression-free survival. The Company expects to trigger the topline analysis from the Phase 3 DeFi trial in the first quarter of 2022 and to report these data during the first half of the year.
Recruitment is ongoing in a Phase 2 study sponsored by the Children’s Oncology Group evaluating nirogacestat in pediatric patients with desmoid tumors.
In November 2021, SpringWorks completed enrollment in the Phase 2b ReNeu trial evaluating mirdametinib in adult and pediatric patients with NF1-associated plexiform neurofibromas (NF1-PN).
Patients continue to be dosed in a Phase 1/2 clinical trial evaluating mirdametinib in children and young adults with low-grade glioma.
B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma

SpringWorks continues to advance nirogacestat as a potential cornerstone of BCMA combination therapy across modalities in collaboration with seven industry leaders.

In October 2021, SpringWorks announced an update from its ongoing clinical collaboration with GlaxoSmithKline evaluating nirogacestat in combination with BLENREP (belantamab mafodotin-blmf) in patients with relapsed or refractory multiple myeloma. The first combination dose level, which is evaluating 0.95 mg/kg Q3W BLENREP plus nirogacestat, has been expanded based on encouraging preliminary data observed in the dose exploration Phase 1 portion of the nirogacestat DREAMM-5 sub-study. Initial clinical data are expected to be presented in mid-2022. The 0.95 mg/kg Q3W BLENREP + nirogacestat cohort has advanced into a randomized Phase 2 expansion and is now enrolling patients to further explore the safety and efficacy profile of the combination versus a 2.5 mg/kg Q3W BLENREP monotherapy control arm, which is the same as the FDA approved monotherapy dose and schedule of BLENREP. In parallel, additional dose levels and schedules of BLENREP plus nirogacestat continue to be evaluated in the Phase 1 portion of the study. In addition, two new sub-studies will evaluate the BLENREP plus nirogacestat combination together with standard-of-care multiple myeloma therapies in the DREAMM-5 trial (pomalidomide plus dexamethasone and lenalidomide plus dexamethasone). Data from these two new sub-studies may enable future clinical trials in earlier lines of multiple myeloma.
In December 2021, the Company entered into a clinical trial collaboration agreement with AbbVie, Inc. to evaluate nirogacestat in combination with ABBV-383, AbbVie’s investigational CD3 bispecific antibody directed against BCMA, in patients with relapsed or refractory multiple myeloma.
In December 2021, SpringWorks announced that the first patient has been dosed in a Phase 1b/2 trial evaluating nirogacestat with elranatamab (PF-06863135), Pfizer’s investigational BCMA CD3-targeted bispecific antibody, in patients with relapsed or refractory multiple myeloma.
In addition to the current ongoing studies, SpringWorks expects that a Seagen-sponsored trial of nirogacestat + SEA-BCMA and an AbbVie-sponsored Phase 1b trial of nirogacestat + ABBV-383 will each initiate enrollment in the first half of 2022.
Biomarker-Defined Metastatic Solid Tumors

Enrollment is ongoing in a Phase 1b/2 trial evaluating mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors. Initial clinical data from the BeiGene-sponsored trial are expected to be presented at an upcoming SpringWorks-sponsored R&D Day.
Enrollment is ongoing in a Phase 1 trial of BGB-3245 in adult patients with RAF mutant solid tumors. BGB-3245 is a selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene. Initial clinical data from the MapKure-sponsored trial are expected to be presented at an upcoming SpringWorks-sponsored R&D Day.
Enrollment is ongoing in a Phase 1b/2a platform study sponsored by Memorial Sloan Kettering Cancer Center evaluating mirdametinib both as a monotherapy and as a combination therapy in advanced solid tumors harboring selected MAPK-activating mutations.
Preclinical data from the TEAD inhibitor program are expected to be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2022.
In October 2021, SpringWorks entered into an exclusive worldwide license agreement with Dana-Farber Cancer Institute (Dana-Farber) and a sponsored research agreement with Stanford Medicine for a portfolio of novel small molecule inhibitors of Epidermal Growth Factor Receptor (EGFR) designed for the treatment of EGFR-mutant cancers. In addition, SpringWorks entered into a collaboration agreement with Ab Magnitude Ventures Group, LLC and Ab Magnitude Fund, LP (collectively, "Ab Magnitude") to collaborate on target discovery and initial hit finding to advance next generation oncology therapeutics. SpringWorks and Ab Magnitude will also collaborate on the portfolio of EGFR inhibitors in-licensed by SpringWorks from Dana-Farber, with Ab Magnitude supporting optimization and characterization of the portfolio using its computational structural biology platform.
Fourth Quarter and Full Year 2021 Financial Results

Revenue: SpringWorks did not recognize any revenue for the fourth quarter or year ended December 31, 2021, and the Company does not currently have any sources of recurring revenue. The fourth quarter and full year 2020 included revenue of $35.0 million, attributable to the nonrefundable upfront payment from Jazz Pharmaceuticals in October 2020, related to the asset purchase and exclusive license agreement between SpringWorks and Jazz Pharmaceuticals under which Jazz acquired SpringWorks’ fatty acid amide hydrolase (FAAH) inhibitor program.
Research and Development (R&D) Expenses: R&D expenses were $29.3 million and $101.7 million for the fourth quarter and full-year periods, respectively, compared to $15.3 million and $51.9 million for the comparable periods of 2020. The increases in R&D expenses were attributable to an increase in internal costs driven by the growth in employee costs associated with increases in the number of R&D personnel and an increase in stock-based compensation expense as well as an increase in external costs related to drug manufacturing and trial costs, as well as the $11.0 million nonrefundable upfront payment for the in-licensing of the TEAD inhibitor program.
General and Administrative (G&A) Expenses: G&A expenses were $26.5 million and $71.8 million for the fourth quarter and full-year periods, respectively, compared to $8.5 million and $29.5 million for the comparable periods of 2020. The increases in G&A expenses were primarily attributable to the hiring of additional personnel in our G&A functions as we continued to expand our operations to support the organization, including commercialization preparation efforts that are underway, and an increase in stock-based compensation expense. In addition, G&A expenses included an increase in information technology costs, and consulting and professional services, including legal, regulatory and compliance.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $56.1 million, or $1.15 per share, for the fourth quarter of 2021 and a net loss of $173.9 million, or $3.59 loss per share, for the year ended December 31, 2021. This compares to net income of $11.3 million, or $0.23 per share, for the fourth quarter of 2020 and a net loss of $45.6 million, or $1.05 per share for the year ended December 31,2020.
Cash Position: Cash, cash equivalents and marketable securities were $432.7 million as of December 31, 2021.
COVID-19 Update

To date, the COVID-19 pandemic has had a relatively modest impact on SpringWorks’ business operations, in particular on SpringWorks’ clinical trial programs, and SpringWorks is undertaking considerable efforts to mitigate the various challenges presented by this crisis. For further details and descriptions of the risks associated with the COVID-19 pandemic, please see the Risk Factors in SpringWorks’ periodic filings with the Securities and Exchange Commission and refer to the Forward-Looking Statements section in this press release.

On February 24, 2022 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported that members of the Silverback management team will participate in the 42nd Annual Cowen Healthcare Conference from March 7-9, 2022 (Press release, Silverback Therapeutics, FEB 24, 2022, View Source [SID1234608989]).

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Laura Shawver, Ph.D., Silverback’s Chief Executive Officer, will present a corporate overview on Wednesday, March 9th, 2022, at 12:50 p.m. ET (9:50 a.m. PT). The live webcast of the presentation will be available on Silverback’s Investor Relations website and a replay will be available for 30 days following the event. Members of the Silverback management team will also host investor meetings during the conference.

On February 24, 2022 A Columbus pharmaceutical reported that has raised $40 million toward a drug that could slow progression of a type of treatment-resistant metastatic breast cancer – all because a grad student at Duke University five years ago happened to grab a vial of the once-abandoned osteoporosis treatment (Press release, Sermonix Pharmaceuticals, FEB 24, 2022, View Source [SID1234608988]).

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Sermonix Pharmaceuticals Inc. is awaiting data from more than 100 patients treated over the past two years. If results show significant benefit, the company could seek a meeting this summer with the U.S. Food and Drug Administration to map out next steps, COO Dr. Miriam Portman said.

The company licensed the drug lasofoxifene in 2015 to renew efforts toward approval as an osteoporosis treatment, but quickly changed purpose when Duke identified potential in breast cancer. That use has since shown promising results in mice. The FDA granted fast-track status to the study in 2019.

"It was really an ‘aha moment’ and a huge pivot point for us," said Dr. David Portman, Sermonix CEO. "The company is confident in the activity of the drug, and is hopeful to get breakthrough designation and get the drug to availability to patients in the coming years."

Perceptive Xontogeny Ventures led the Series A3 round in November with some repeat investors. Perceptive partners Fred Callori and Ben Askew joined the Sermonix board. The company previously raised seed funding and a $20 million round in 2019.

Sermonix plans to open a downtown office this spring, and some Philadelphia-area executives with pharmaceutical industry experience plan to move, David Portman said. The funding will help it wrap up the two clinical trials, pursue regulatory approval and increase manufacturing of both the drug and a companion diagnostic test for the type of cancer it targets.

The Portmans, physicians who are married and live in Bexley, founded Columbus Center for Women’s Health Research in 1997 to conduct clinical studies on hormone therapy, osteoporosis, contraception and heart disease. It was acquired by another Columbus research business in 2015. They formed Sermonix and licensed lasofoxifene from Ligand Pharmaceuticals Inc.

San Diego-based Ligand developed the drug in a collaboration with Pfizer Inc. in the 1990s. The hormonal therapy is a selective estrogen receptor modulator (or SERM, hence Sermonix) – basically fooling estrogen receptors to slow diseases stimulated by the hormone. But attempts at FDA approval hit a road block in 2009, and Pfizer went with a different compound. Rights later reverted to Ligand.

Sermonix’s license entitles Ligand to as much as $45 million in milestone payments and 6% to 10% royalties on any eventual sales, according to regulatory filings.

Meanwhile, Donald McDonnell, who was on the inventing team at Ligand before moving to Duke, had become co‐director of Duke Cancer Institute’s program in women’s cancer.

Treatments that inhibit the production or uptake of estrogen are effective against types of breast tumors stimulated by the hormone – but those tumors often mutate to resist the therapy.

Researchers in McDonnell’s lab in 2016 were studying a specific mutation that’s diagnosed in about 20,000 patients a year. A graduate student was working with ovarian tumor cells with the same mutation, and started testing every known hormonal treatment on them, according to the institute’s website.

Lasofoxifene – on hand only because of McDonnell’s Ligand work – was the only one that slowed growth.

"He had some of that compound on his shelf," David Portman said. "It showed very unexpected activity. It was a fortunate series of events."

Duke patented the application for breast cancer, and started working with Sermonix, the license-holder, toward commercialization. The company has a video explaining how it works.

"That was a significant unmet medical need and a far greater medical benefit to patients than what we were currently working on," David Portman said.

Because of the earlier osteoporosis studies, the drug could skip over the first phase showing it’s safe for use in humans. Two trials are wrapping up comparing the current standard of care for treatment-resistant cancer against lasofoxifene; one uses it alone and the other in combination with a second drug.

Breast cancer with this mutation is incurable once at this stage, but the therapy aims to slow progression and spread, making it a manageable chronic condition.

Perceptive Xontogeny, a joint fund of New York City and Boston firms, also was the lead investor in the $40 million 2020 round that launched Grove City gene therapy startup Forge Biologics Inc., part of a fast-growing Central Ohio biotech sector.

"It felt very lonely for a while, and now it’s started to grow significantly," David Portman said. "It is becoming an exciting hub."

On February 24, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported financial results for the fourth quarter and full year ended December 31, 2021, and provided its financial outlook for 2022 (Press release, Schrodinger, FEB 24, 2022, View Source [SID1234608987]).

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Schrödinger also announced today the promotion of Karen Akinsanya, Ph.D., from executive vice president and chief biomedical scientist to president of R&D, therapeutics. The promotion reflects Dr. Akinsanya’s extraordinary contributions to leading Schrödinger’s drug discovery team, which leverages the company’s platform at scale, as well as her strategic contributions to expanding and advancing the company’s collaborative and wholly-owned programs.

"We are very pleased to have delivered a strong year, capped by fourth quarter software revenue of $38.6 million, a 55 percent increase over the fourth quarter of 2020. Looking ahead, we expect continued scale up and adoption of our software platform as our collaborators and customers continue to experience success in rapidly generating high-quality molecules to advance the next generation of therapeutics and materials," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "I’m also thrilled to announce Karen’s promotion today. Karen came to Schrödinger in 2018 with a vision to transform and accelerate drug discovery and has made incredible progress building a pipeline and a team that spans discovery to early clinical development."

"Our software platform is critical to our success in both our collaborative and internal drug discovery pipeline, and we are pleased to see multiple programs advance into preclinical and clinical development. This includes seven collaborative programs that have advanced into the clinic, which underscores the impact of our platform," stated Dr. Akinsanya. "Our internal pipeline is also advancing, and later this year we expect to initiate our first Phase 1 clinical study of our MALT1 inhibitor in patients with relapsed and resistant lymphoma."

2022 Financial Outlook

As of February 24, 2022, Schrödinger outlined the following expectations for the fiscal year ending December 31, 2022:

Total revenue expected to range from $161 million to $181 million, representing 17 percent to 31 percent growth over 2021

Total software revenue expected to range from $126 million to $136 million, representing 11 percent to 20 percent growth over 2021

Total drug discovery expected to range from $35 million to $45 million, representing 42 to 82 percent growth over 2021

Operating expense growth is expected to be slightly lower than the 42 percent reported for the year ended December 31, 2021

Software gross margin percentage is expected to be in the mid-70s

For the first quarter of 2022, software revenue is expected to range from $28 to $30 million.

2022-2023 Key Strategic Goals

Today, Schrödinger laid out the following strategic objectives for 2022-2023:

Ongoing growth in adoption and scale up of software platform, with target ACV growth of over 20 percent in 2023

Inflection in drug discovery revenue in 2023, with target 2023 drug discovery revenue of at least $100 million – excludes potential revenue from partnering the company’s three lead internal programs

IND submission for the MALT1 program in first half of 2022, IND submission for the CDC7 program in early 2023 and IND submission for the Wee1 program in 2023

Initiate a Phase 1 clinical study for the MALT1 program in the second half of 2022, and initiate Phase 1 clinical studies for the CDC7 and Wee1 programs in 2023

Publication of data from internal programs in peer-reviewed forums, including presentation of preclinical data from the Wee1 program in the first half of 2022

Multiple new internal programs leveraging internal structural biology capabilities

Materials science collaborations in multiple verticals, such as clean energy and sustainable materials

Recent Business Highlights

Internal Pipeline

Presented preclinical data from MALT1 program at ASH (Free ASH Whitepaper): In December, Schrödinger presented preclinical data on the company’s MALT1 allosteric inhibitor program at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrating that its MALT1 inhibitors showed single agent and combination anti-tumor activity with approved anti-cancer therapies in preclinical models of B-cell lymphoma. The data presented suggest that targeting MALT1 may expand therapeutic options for patients with selected B-cell lymphomas, such as activated B-cell subtype of diffuse large B cell lymphoma, with the possibility of expanding into other B-cell lymphomas such as mantle cell lymphoma.

Expanded internal pipeline: During 2021, Schrödinger added two new programs to its internal pipeline in the areas of oncology and immunology.

Collaborative Programs

In January 2022, Nimbus announced initiation of a Phase 2b study of its investigational oral allosteric TYK2 inhibitor in patients with active psoriatic arthritis.

In November 2021, Nimbus announced the initiation of its first-in-human Phase 1/2 study of its HPK1 inhibitor, NDI-101150, in patients with solid tumors.

Underlying Science

Published 27 peer-reviewed papers across life sciences and materials science in 2021: During 2021, Schrödinger scientists continued to make scientific advances and were authors on 27 publications in peer-reviewed life sciences and materials sciences journals. Recent publications include an article in collaboration with Janssen to assess the performance of affinity predictions as well as data from a collaboration with scientists at Samyang Corp. aimed at accelerating the design of photoinitiators, which are light sensitive molecules used in inks and coatings, adhesives and other products.

Corporate

Acquired XTAL Biostructures to expand structural biology capabilities: Last month, Schrödinger announced the $6 million all-cash purchase of XTAL BioStructures, Inc., a private company based in the Greater Boston area that provides structural biology services, including biophysical methods, protein production and purification, and X-ray crystallography, to the pharmaceutical and biotechnology industries. The acquisition of XTAL BioStructures enables Schrödinger to pursue scientific advancements in the field of structural biology, augment its ability to produce high quality target structures for its drug discovery programs, and expand its future offerings to include an advanced and differentiated service that provides

customers access to protein structures that have been computationally validated and are ready for structure-based virtual screening and lead optimization.

Established operations in South Korea and expanded presence in India: In January 2022, Schrödinger established operations in Seoul, South Korea to strengthen its global expansion efforts, enhance competitive positioning and support both life science and materials sciences customers in this region. In December 2021, Schrödinger expanded its operations in Hyderabad, India. Employees in the Hyderabad location will focus on a broad range of strategic initiatives across the company, including software development and support of Schrödinger’s software platform, and its drug discovery programs.

Webcast and Conference Call Information

Schrödinger will host a conference call to discuss its fourth quarter and full year 2021 financial results on Thursday, February 24, 2022, at 4:30 p.m. ET. To participate in the live call, please dial (833) 727-9520 (domestic) or +1 (830) 213-7697 (international) and refer to conference ID 3169814. The webcast can also be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

On February 24, 2022 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, reported fourth quarter and full year 2021 financial results and recent business highlights (Press release, Sangamo Therapeutics, FEB 24, 2022, View Source [SID1234608986]).

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"In 2021, we continued to advance the development of genomic medicines for patients across multiple therapeutic areas using our innovative technologies," said Sandy Macrae, Chief Executive Officer of Sangamo. "We along with our partners presented compelling clinical data in our three lead programs and advanced development of preclinical product candidates using our second-generation technologies of CAR-Treg cell therapy for autoimmune diseases and engineered zinc finger transcription factors for neurological disorders. In addition, we completed and brought online our cell therapy manufacturing facilities in Brisbane and Valbonne and now have operational AAV and cell therapy facilities in-house. We believe this progress positions us well to generate long-term value for our shareholders."
Fourth Quarter Updates and Recent Business Highlights
Fabry disease – Updated preliminary Phase 1/2 data show continued safety, tolerability and elevated α-Gal A enzyme activity; Phase 3 planning initiated
•We presented updated preliminary clinical data from the Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, our wholly owned gene therapy product candidate for the treatment of Fabry disease at the 18th Annual WORLDSymposium earlier this month. As of the November 9, 2021 cutoff date:
◦The four patients in Cohorts 1 and 2 all exhibited above normal α-Gal A activity, ranging from 3-fold to 15-fold above mean normal at last measurement.
◦The two patients in Cohort 1 maintained elevated α-Gal A activity for one year and are now in the long-term follow-up study.
◦The first patient in Cohort 3 exhibited α-Gal A activity within mean normal range by week 2.
◦Lyso-Gb3 levels remained significantly reduced in the patient who exhibited the highest baseline levels of this biomarker.
◦The gene therapy candidate continued to be generally well tolerated in the five treated patients.
•The sixth patient in the STAAR study, who is the second patient in Cohort 3, was dosed after the cutoff date. We expect to provide updated data in the second half of 2022.
•Based on the Phase 1/2 data, we have initiated Phase 3 planning.
Sickle cell disease – Updated preliminary Phase 1/2 proof-of-concept safety, tolerability and efficacy results
•We presented updated preliminary proof-of-concept clinical data from the Phase 1/2 PRECIZN-1 study of SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development with Sanofi, at the 63rd American Society for Hematology Annual Meeting and Exposition (ASH 2021). As of the September 22, 2021 cutoff date:
◦No adverse events related to SAR445136 were reported.
◦All four treated patients experienced increases in total hemoglobin, fetal hemoglobin and percent F cells.
◦None of the patients required blood transfusions post engraftment.
•We expect that the next four patients treated in the study will be dosed with a product candidate manufactured using improved methods, which have been shown in internal experiments to increase long-term progenitor cells. We expect to complete dosing of these patients in the third quarter of this year.

•We and Sanofi are collaborating on an orderly transition of Sanofi’s rights and obligations under the program to Sangamo on June 28, 2022, while we explore options to advance the program, including seeking a potential new partner.
Hemophilia A – Updated Phase 1/2 results show sustained bleeding control in highest dose cohort through two years following giroctocogene fitelparvovec gene therapy
•With our collaborator Pfizer, we presented updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A, at ASH (Free ASH Whitepaper) 2021. As of the October 1, 2021 cutoff date:
◦At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort had resumed prophylaxis.
◦Giroctocogene fitelparvovec continued to be generally well-tolerated.
•Regarding the Phase 3 AFFINE trial of giroctocogene fitelparvovec, Pfizer has announced that it hopes to obtain agreements from health authorities to resume the AFFINE trial and to begin to reopen trial sites in the first half of 2022. This trial was previously paused when some of the patients treated in this trial experienced FVIII activity greater than 150% following treatment. Pfizer has announced that it currently is in the process of submitting a protocol amendment to health authorities in the countries where this trial is being conducted and preparing responses to the U.S. FDA clinical hold. Over 50% of the patients have been enrolled in the Phase 3 AFFINE trial.
Renal Transplant Rejection – First patient enrolled and expected to be dosed soon in Phase 1/2 study
•The first patient has been enrolled and is expected to be dosed soon in our Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous HLA-A2 CAR Treg cell therapy product candidate treating patients receiving an HLA-A2 mismatched kidney from a living donor. We expect the second patient in this study to be dosed by the middle of 2022. We continue to open study sites and screen patients.
Manufacturing – AAV and cell therapy cGMP manufacturing facilities fully operational
•We completed and brought online our in-house cell therapy manufacturing facilities in our Brisbane, California headquarters and in our Valbonne, France facilities in 2021, in addition to the in-house AAV manufacturing facilities we brought online in Brisbane in 2020.
Fourth Quarter and Full Year 2021 Financial Results
Consolidated net loss for the fourth quarter ended December 31, 2021 was $37.5 million, or $0.26 per share, compared to net loss of $40.7 million, or $0.29 per share, for the same period in 2020. For the year ended December 31, 2021, consolidated net loss was $178.3 million, or $1.23 per share, compared to consolidated net loss of $121.1 million, or $0.90 per share, for the year ended December 31, 2020.
Revenues
Revenues for the fourth quarter ended December 31, 2021 were $28.0 million, compared to $25.8 million for the same period in 2020.
The increase of $2.2 million in revenues was primarily due to increase in recognition of upfront license fees and research revenue of $3.7 million under our collaboration agreement with Novartis. The increase was partially offset by a decrease of $1.4 million in revenue related to the termination of our licensing agreement with Dow AgroSciences LLC in July 2021.
Revenues were $110.7 million in 2021, compared to $118.2 million in 2020. The decrease in revenues was primarily due to a decrease of $47.4 million of milestone fees and recognition of upfront license fees related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer resulting from the completion of our activities in 2020 and a decrease of $5.4 million from our collaboration agreements with Kite and Sanofi. These decreases were partially offset by higher revenues of $32.7 million and $14.4 million related to our collaboration agreements with Novartis and Biogen, respectively.
Total operating expenses on a GAAP basis for the fourth quarter ended December 31, 2021 were $67.9 million compared to $69.2 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the fourth quarter ended December 31, 2021 were $59.8 million, compared to $62.6 million for the same period in 2020.
The decrease in total operating expenses in the fourth quarter on a GAAP basis was primarily due to a reduction of research and development expenses by $5.2 million related to dissolution of the repayment obligation of a grant from California Institute for Regenerative Medicine associated with the discontinuation of the ST-400 program. This decrease was partially offset by an increase of $4.6 million in research and development expenses due to increased headcount to support the advancement of our clinical trials and our ongoing collaborations, and an increase in manufacturing and overhead costs as we ramped up our internal manufacturing operations.
Total operating expenses on a GAAP basis in 2021 were $294.0 million compared to $247.7 million in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, were $261.0 million and $222.0 million in 2021 and 2020, respectively.
The increase in total operating expenses in the full year on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our ongoing collaborations and an increase in manufacturing and overhead costs as we ramped up our internal manufacturing operations.
Cash, cash equivalents and marketable securities
Cash, cash equivalents and marketable securities as of December 31, 2021 were $464.7 million compared to $692.0 million as of December 31, 2020.
Initial Financial Guidance for 2022
On a GAAP basis, we expect total operating expenses in the range of approximately $320 million to $350 million in 2022, which includes non-cash stock-based compensation expense.
We expect non-GAAP total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $40 million, in the range of approximately $280 million to $310 million in 2022.
Conference Call
Sangamo will host a conference call today, February 24, 2022, at 4:30 p.m. Eastern Time, which will be open to the public. The call will also be webcast with live Q&A and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.
The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 2235808. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 2235808.