On March 10, 2022 Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company pioneering the development of exosome-based therapeutics as a new class of medicines, reported fourth quarter and full year 2021 financial results and recent operational progress (Press release, Codiak Biosciences, MAR 10, 2022, View Source [SID1234609889]).

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"We are making a strong start in 2022 thanks to progress with our development programs in 2021 and into this year, and plan to report clinical data for two of our engineered exosome therapeutic candidates and initiate clinical development for a third candidate all in the first half of the year," said Douglas E. Williams, Ph.D., President and CEO of Codiak. "The platform we’ve developed at Codiak allows us to deliver multiple classes of therapeutics with a high degree of precision to specific cells and our clinical data from two programs has already shown promising safety and predictable PK/PD relationships. The emergence of programs in vaccines and gene delivery highlight the breadth of opportunity across multiple therapeutic areas with the engEx platform."

Fourth Quarter 2021 and Recent Highlights

Reported positive initial data from dose cohorts 1-3 in the Phase 1/2 clinical trial of exoSTING (CDK-002) for the treatment of advanced/metastatic, recurrent and injectable solid tumors; progressed subject dosing to cohorts 4 and 5 and follow up in all dose cohorts

Advanced cutaneous T cell lymphoma (CTCL) portion of Phase 1 trial of exoIL-12 (CDK-003)

Filed and received U.S. FDA clearance of Investigational New Drug (IND) application for exoASO-STAT6 (CDK-004) for the intravenous treatment of hepatocellular carcinoma

Presented three abstracts at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), including new preclinical data on exoASO-STAT6 in hepatocellular carcinoma, exoSTING in leptomeningeal disease and the combination of exoSTING and exoIL-12 in solid tumors

Announced new preclinical data from the exoVACC exosome-based vaccine platform at the World Vaccine & Immunotherapy Congress (WVIC) 2021

Published a manuscript describing the full exoASO-STAT6 preclinical program in the American Association for the Advancement of Science’s journal, Science Advances

Anticipated Milestones and Events

Safety, PK, PD, and objective response rate (ORR) data from dose escalation cohorts 1-5 in the Phase 1/2 trial of exoSTING and recommended Phase 2 dose expected in late 1H 2022

First-in-human dosing for exoASO-STAT6 in a Phase 1 clinical trial in hepatocellular carcinomas anticipated in 1H 2022

Initial safety, PK/PD and efficacy data in CTCL patients in the Phase 1 clinical trial of exoIL-12 anticipated in late 1H 2022. While COVID-related restrictions in the UK that impacted clinical trial sites last year are abating, Codiak continues to work with those sites to explore options to facilitate enrollment.

Poster presentation of preclinical data for exoASO-C/EBPß, a proprietary engineered exosome loaded with antisense oligonucleotides targeting C/EBPß, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held April 8-13, 2022

Presentation of new preclinical data from the exoVACC pan-beta coronavirus vaccine program, as part of Codiak’s collaboration with the Ragon Institute, at the World Vaccine Congress, to be held April 18-21, 2022

Fourth Quarter and Full Year 2021 Financial Results

Total revenues for the quarter ended December 31, 2021 were $7.7 million, compared to $1.6 million for the same period in 2020. Total revenues for the year ended December 31, 2021 were $22.9 million, compared to $2.9 million for the same period in 2020. These increases were primarily driven by revenue recognized from the Jazz collaboration for $10.9 million as a result of the mutual decision to discontinue work on STAT3 in Q1 2021 and the early termination of the research agreement with Sarepta, for $7.0 million in Q4 2021.

Net income for the quarter ended December 31, 2021 was $16.7 million, compared to a net loss of $18.0 million for the same period in 2020. Net loss for the year ended December 31, 2021, was $37.2 million, compared to a net loss of $91.7 million for the same period in 2020. The decrease in net loss for the fourth quarter and year was driven primarily by a gain on disposition of $33.3 million related to the agreement with Lonza, as well as collaboration revenue recognition in 2021.

Research and development expenses were $17.4 million for the quarter ended December 31, 2021, compared to $13.3 million for the same period in 2020. The increase in research and development expenses for the quarter was driven primarily by an increase in personnel-related costs and ongoing development of the engEx Platform.

Research and development expenses were $64.9 million for the year ended December 31, 2021, compared to $74.0 million for the same period in 2020. The year-over-year decrease was primarily driven by a licensing payment to Kayla Therapeutics in September 2020, offset by increases in clinical development costs for exoIL-12, exoSTING, and exoASO-STAT6 in 2021.

General and administrative expenses were $6.9 million for the quarter ended December 31, 2021, compared to $5.9 million for the same period in 2020. General and administrative expenses were $27.6 million for the year ended December 31, 2021, compared to $19.9 million for the same period in 2020. These increases were driven primarily by an increase in personnel costs and costs associated with transitioning to a public company.

As of December 31, 2021, Codiak had cash and cash equivalents of approximately $76.9 million.

On March 10, 2022 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported financial results for the fourth quarter and year ended December 31, 2021 (Press release, Corvus Pharmaceuticals, MAR 10, 2022, View Source [SID1234609888]).

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"We continue to advance three clinical programs for novel product candidates targeting CD73, the adenosine 2A receptor, and ITK, which are involved in immune response to cancers and other diseases," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We have established sound scientific foundations for our product candidates, which give us confidence as we initiate mid-stage clinical trials in front-line treatment of lung cancer and renal cell cancer. In addition, our partnership with Angel Pharmaceuticals has expanded the clinical development of CPI-818 for T cell lymphomas into China and is accelerating global development of this product candidate."

Mupadolimab (anti-CD73)

The Company plans to initiate a randomized Phase 2 clinical trial evaluating mupadolimab as a front-line therapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC). The randomized, blinded trial will compare standard chemotherapy plus pembrolizumab (anti-PDL-1) with or without mupadolimab. The Company intends to enroll approximately 150 patients with any tumor PDL-1 expression in the clinical trial, potentially addressing a large patient population. The primary endpoint for the study will be progression free survival and secondary endpoints will evaluate objective response rate and overall survival.
The Company continues to enroll its two Phase 1b/2 clinical trial expansion cohorts of patients with (1) head and neck cancers that have failed previous treatment with anti-PD-1 therapy and chemotherapy and (2) relapsed refractory NSCLC who have failed previous treatment with anti-PD(L)-1 therapy and chemotherapy. Up to 15 patients will be enrolled in each expansion cohort and initial results are anticipated to be presented in the second half of 2022.
In November 2021, the Company presented results from its Phase 1/1b clinical trial that, along with pre-clinical data, provided further evidence regarding mupadolimab’s mechanism of action and its potential anti-tumor activity in cancer patients. The data showed that mupadolimab doses of 12mg/kg or greater, resulted in complete occupancy of the CD73 target and B cell activation. In the assessment of anti-tumor activity in sixteen evaluable patients receiving the 12mg/kg or greater doses of mupadolimab, tumor regression (not meeting the threshold for partial response by RECIST) was seen in five patients who had progressive disease as the best response to most recent prior therapy, which included anti-PD(L)1. We believe these interim findings support mupadolimab’s potential to cause tumor regression in patients with tumors refractory to anti-PD(L)1.
CPI-818 (selective ITK inhibitor)

The Company’s partner in China, Angel Pharmaceuticals, initiated patient enrollment in a Phase 1/1b clinical trial of CPI-818 for the treatment of refractory T cell lymphomas. Angel Pharmaceuticals is responsible for all expenses related to conducting the clinical trial in China.
The Company continues to enroll patients in its Phase 1/1b clinical trial, which was expanded to include patients with certain types of T cell leukemias in addition to T cell lymphomas.
Based on interim results observed in patients with peripheral T cell lymphoma (PTCL) in these Phase 1/1b clinical trials, the Company believes such results could provide the foundation for a potential global phase 2 clinical trial in advanced PTCL.
Ciforadenant (adenosine 2a receptor antagonist)

The Company plans to collaborate with the Kidney Cancer Clinical Trials Consortium to initiate an open-label Phase 2 clinical trial evaluating ciforadenant as a first-line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-PD-1) and nivolumab (anti-CTLA-4). The clinical trial will enroll up to 60 patients and is intended to evaluate the potential for ciforadenant to generate increased complete responses and deep responses in the front-line setting. The Kidney Cancer Clinical Trials Consortium is comprised of a group of leading cancer centers in the United States led by investigators at MD Anderson. The trial design is based on Corvus’ preclinical research published in 2018 in Cancer Immunology Research that demonstrated impressive antitumor control and cures in several animal models using ciforadenant in combination with anti-CTLA4 and anti-PD1.
The Company continues to advance its understanding of the Adenosine Gene Signature biomarker, which has been confirmed by other groups as a means to identify an unfavorable group of renal cell cancer patients. Tumor biopsies from the Phase 2 clinical trial will be evaluated for expression of the Adenosine Gene Signature.
Financial Results
As of December 31, 2021, Corvus had cash, cash equivalents and marketable securities totaling $69.5 million compared to $44.3 million as of December 31, 2020. Corvus expects full year 2022 net cash used in operating activities to be between $34 million and $36 million.

Research and development expenses for the three months and full year ended December 31, 2021 totaled $4.8 million and $29.1 million, respectively, compared to $7.2 million and $31.8 million for the same periods in 2020. In the fourth quarter of 2021, the decrease of $2.4 million was primarily due to a decrease in clinical trial and personnel costs.

Net loss for the three months and full year ended December 31, 2021 was $9.2 million and $43.2 million, respectively, compared to net income of $27.3 million and a net loss of $6.0 million for the same periods in 2020. Results for the year ended December 31, 2020 included a $37.5 million gain from the deconsolidation of Angel Pharmaceuticals. Total stock compensation expense for the three months and year ended December 31, 2021 was $0.7 million and $4.2 million, respectively, compared to $1.2 million and $5.7 million for the same periods in 2020.

Conference Call and Webcast
Corvus will host a conference call and webcast today, March 10, 2022, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter and full year 2021 financial results. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) and using the conference ID 13727689. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On March 10, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing a first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported business updates, upcoming milestones and financial results for the fourth quarter and year ended December 31, 2021 (Press release, Geron, MAR 10, 2022, View Source [SID1234609887]). The Company ended 2021 with $212.7 million in cash and marketable securities, which the Company believes is sufficient to fund current operations through the end of the first quarter of 2023.

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"We made significant accomplishments in 2021 to advance the development of imetelstat toward two important Phase 3 data readouts, which if positive, have the potential to transform patient care in lower risk MDS and refractory MF," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "With completion of enrollment in IMerge Phase 3 last October, we look forward to top-line results from that trial in early January 2023. If those results confirm similar safety, as well as the depth, breadth and durability of transfusion independence that was observed in our Phase 2 trial, then upon approval of an NDA, we expect our U.S. commercial launch of imetelstat in lower risk MDS to occur as early as the first half of 2024."

Dr. Scarlett added, "In 2021, we also made progress with the IMpactMF Phase 3 trial in refractory MF, by opening 50% of the planned clinical sites to patient enrollment. In 2022, we plan to open the rest of the selected clinical sites to enable the planned interim analysis in 2024."

Dr. Scarlett also noted, "Building on the strong evidence of imetelstat’s disease modification potential from our Phase 2 trials, we started several new programs in 2021. We believe that the data to be generated from these programs over the next few years will provide strategic value to the imetelstat franchise through the potential expansion into new myeloid and lymphoid hematologic indications, as well as into combination regimens."

Key Upcoming Milestones Expected

Top-line results from IMerge Phase 3 in early January 2023
Open the rest of the selected clinical sites in IMpactMF for enrollment to enable the planned interim analysis in 2024
Expand into additional indications and treatment combinations:
Start of IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in 1H 2022
Start of IMpress Phase 2 study of single-agent imetelstat in R/R AML and HR MDS in 2H 2022
Start of TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R AML in 2H 2022
Top-Line Results Expected in Early January 2023 from IMerge Phase 3 in Lower Risk Myelodysplastic Syndromes (MDS)

Assuming the results of IMerge Phase 3 support regulatory submissions, Geron plans to submit a New Drug Application (NDA) in the United States in the first half of 2023 and a Marketing Authorization Application (MAA) in Europe in the second half of 2023 for imetelstat in lower risk MDS. Upon potential approval by the United States Food and Drug Administration (FDA) of the NDA, the Company expects that its commercial launch of imetelstat in lower risk MDS in the United States could occur as early as the first half of 2024.

Planned Interim Analysis in 2024 from IMpactMF in Refractory Myelofibrosis (MF)

IMpactMF, the only Phase 3 clinical trial in MF with overall survival (OS) as a primary endpoint, is planned to engage approximately 180 clinical sites across North America, South America, Europe, Australia and Asia to facilitate patient recruitment and enrollment into the trial. The Company expects to open for enrollment the remaining approximately 50% of selected clinical sites in 2022.

Under current planning assumptions around enrollment and median overall survival for each treatment arm, the Company expects to conduct the interim analysis in 2024 and the final analysis in 2025. The final analysis for OS is planned to be conducted after more than 50% of the patients enrolled in the trial have died. An interim analysis of OS is planned to be conducted after approximately 70% of the total projected number of events for the final analysis have occurred. If the pre-specified, statistically significant difference in OS between the two treatment arms is met at the interim analysis, it is possible that data from the interim analysis could support a registration filing. Both the planned interim and final analyses are event-driven and could occur on different timelines than currently expected.

Pipeline Expansion to Enhance Imetelstat Potential

In November 2021, the Company unveiled three new clinical programs and one preclinical program for imetelstat. These programs explore the use of imetelstat as a single agent and in combination with current standard of care therapies to expand the potential application of imetelstat.

In the first half of 2022, Geron plans to initiate IMproveMF, a company-sponsored Phase 1 study of imetelstat in combination with ruxolitinib in frontline MF patients. In addition, in collaboration with key opinion leaders with expertise in acute myeloid leukemia (AML), the Company is supporting investigator-led studies in relapsed/refractory AML and higher risk MDS (HR MDS) to evaluate imetelstat as a single agent and in combination with venetoclax or hypomethylating agents (HMAs). These studies are expected to start in the second half of 2022. The preclinical program in lymphoid malignancies is being conducted at MD Anderson Cancer Center, and the Company expects preliminary results from ongoing in vitro and in vivo experiments to be available by the end of 2022.

Fourth Quarter and Full Year 2021 Results

For the fourth quarter of 2021, the Company reported a net loss of $32.0 million, or $0.10 per share, compared to $23.8 million, or $0.07 per share, for the fourth quarter of 2020. Net loss for the full year of 2021 was $116.1 million, or $0.35 per share, compared to $75.6 million, or $0.28 per share, for the full year of 2020.

Revenues for the three and twelve months ended December 31, 2021 were $1.0 million and $1.4 million, respectively, compared to $50,000 and $253,000 for the same periods in 2020. Revenues in 2021 and 2020 primarily reflect estimated royalties from sales of cell-based research products from the Company’s divested stem cell assets. In connection with the 2013 divestiture of Geron’s human embryonic stem cell assets, including intellectual property and proprietary technology, to Lineage Cell Therapeutics, Inc. (formerly BioTime, Inc., which acquired Asterias Biotherapeutics, Inc.), Geron is entitled to receive royalties on sales from certain research or commercial products utilizing Geron’s former intellectual property. The increase in revenues in 2021 compared to 2020 primary reflects retroactive royalties of approximately $911,000 on product sales of cell-based research products.

Total operating expenses for the three and twelve months ended December 31, 2021 were $32.0 million and $115.4 million, respectively, compared to $23.3 million and $77.2 million for the same periods in 2020.

Research and development expenses for the three and twelve months ended December 31, 2021 were $24.2 million and $85.7 million, respectively, compared to $16.2 million and $51.5 million for the same periods in 2020. The increase in research and development expenses for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects increased clinical development costs associated with conducting two Phase 3 clinical trials, higher imetelstat manufacturing costs for producing validation batches at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes and higher personnel-related costs for additional headcount.

General and administrative expenses for the three and twelve months ended December 31, 2021 were $7.9 million and $29.7 million, respectively, compared to $7.1 million and $25.7 million, for the same periods in 2020. The increase in general and administrative expenses for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects new costs in connection with pre-commercial activities, including modernizing the internal infrastructure to support a commercial launch, and higher legal costs.

Interest income for the three and twelve months ended December 31, 2021 was $106,000 and $527,000, respectively, compared to $243,000 and $1.8 million for the same periods in 2020. The decrease in interest income for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects lower yields on the Company’s marketable securities portfolio.

Interest expense for the three and twelve months ended December 31, 2021 was $1.1 million and $3.7 million, respectively, compared to $754,000 and $760,000 for the same periods in 2020. In September 2020, the Company secured a new debt facility for up to $75 million. As of December 31, 2021, a total of $50 million has been drawn down under the facility.

Financial Resources and Projected 2022 Financial Guidance

The Company ended 2021 with $212.7 million in cash and marketable securities, which the Company believes is sufficient to fund current operations through the end of the first quarter of 2023.

For fiscal year 2022, under generally accepted accounting principles (GAAP), the Company expects total operating expenses in the range of approximately $155 million to $165 million, which includes non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization. The Company expects non-GAAP total operating expenses for fiscal year 2022, which excludes estimated non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization, in the range of approximately $140 million to $150 million.

The fiscal year 2022 financial guidance reflects costs to support preparatory activities for top-line results in lower risk MDS; NDA and commercial readiness; two ongoing Phase 3 clinical trials and new clinical studies expanding the pipeline; finalizing validation batches of imetelstat at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes; projected increases in headcount and interest payments on outstanding debt.

As of December 31, 2021, the Company had 72 employees. The Company plans to grow to a total of approximately 90 to 100 employees by year-end 2022.

Conference Call

Geron will host a conference call at 4:30 p.m. ET on Thursday, March 10, 2022 to discuss business updates, expected upcoming milestones and fourth quarter and full year 2021 financial results.

A live webcast of the conference call and related presentation will be available on the Company’s website at www.geron.com/investors/events. An archive of the webcast will be available on the Company’s website for 30 days.

Participants may access the webcast by registering online using the following link, View Source Participants that are unable to register online can access the conference call via telephone by dialing domestically +1 (888) 330-2434 or internationally +1 (240) 789-2725. The conference ID is 67335.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

About IMerge Phase 3

IMerge Phase 3 is a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, duration of TI and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. For additional information about IMerge Phase 3, visit ClinicalTrials.gov/NCT02598661.

About IMpactMF

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis (MF) who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

On March 10, 2022 Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, reported its financial results for the fourth quarter and full year 2021 and provided an overview of recent business highlights (Press release, Aligos Therapeutics, MAR 10, 2022, View Source [SID1234609886]).

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"Last year was very productive for our team," said Lawrence Blatt, PhD, MBA, Chairman & CEO of Aligos. "We made great strides in advancing our CHB, NASH and COVID portfolios, which has resulted in 3 drug candidates currently being evaluated in their target patient populations and our 4th drug candidate (CHB siRNA) on track to begin dosing in the clinic in the second half of this year. As a result, we expect multiple important data readouts to occur throughout 2022, including safety and proof of concept data for our CAM, ASO and THR-β drug candidates. These data have the potential to be important drivers of shareholder value and we look forward to sharing them as they emerge."

"In 2021, we received important validation of our expertise in developing oligonucleotide drug candidates when Merck entered into a second NASH research collaboration with Aligos," added Leo Beigelman, PhD, President of Aligos. "We view oligonucleotide approaches as powerful tools for silencing mRNA transcripts in a highly specific and durable manner. These approaches are well adapted to silencing transcripts important in driving the pathogenesis seen in CHB and NASH."

Recent Business Highlights

Aligos Portfolio of Drug Candidates:

Capsid Assembly Modulator (CAM)(ALG-000184)
After demonstrating an acceptable safety and PK profile and similar, robust DNA and RNA suppressive effects in HBeAg-negative subjects at the 50 and 100 mg dose levels and in HBeAg-positive subjects at the 100 mg dose level in 2021, further dose exploration has been initiated for our CAM (ALG-000184). Currently, the 10 mg dose level is being evaluated in HBeAg-negative subjects to better define the dose-response characteristics of ALG-000184. Additionally, based on the marked, best-in-class reductions seen in HBV DNA and RNA levels, we are currently exploring the potential of 300 mg ALG-000184 to reduce HBsAg levels (via the "secondary mechanism of action" of CAMs) in HBeAg-positive subjects. We plan to conduct longer term studies (12 weeks) later this year and share these data at a scientific conference in H2 2022.

Antisense Oligonucleotide (ASO)(ALG-02572)
Recently, our Phase 1a evaluation of single ascending doses (SAD) of subcutaneously administered ALG-020572 in healthy volunteers (HVs) was completed and we initiated the Phase 1b portion of the study (in subjects with chronic hepatitis B (CHB)). Enrollment in the first CHB cohort is now complete. Over this year, we plan to evaluate multiple CHB cohorts at varying dose levels to define the dose-response characteristics and risk-benefit profile of ALG-020572. Safety and antiviral activity data are planned to be shared at a scientific conference in H2 2022.

Small Interfering RNA (siRNA)(ALG-125755)
Phase 1 enabling nonclinical studies for our siRNA (ALG-125755) were initiated in 2021 and remain on track for completion in H1 2022. If positive, we expect these data to enable dosing in a planned Phase 1a/1b study starting in HVs in H2 2022. Dosing in CHB subjects is anticipated to begin in H1 2023. HV data are planned to be shared at a scientific conference in H2 2022.

Thyroid Hormone Receptor – Beta (THR-B)(ALG-055009)
Phase 1 enabling nonclinical studies for our THR-β drug candidate (ALG-055009) were completed in 2021, which enabled initiation of a SAD study in HVs in Q4 2021. Administration of single doses in HVs and multiple doses in subjects with hyperlipidemia is ongoing. Topline data, including safety, PK, and pharmacodynamic (lipid) data, are expected in Q3 2022. We also plan to share these data at a scientific conference in H2 2022.

SARS-CoV-2 3CL Protease Inhibitor (COVID-PI)
Multiple COVID-PIs which are more potent in vitro than nirmatrelvir and do not require ritonavir boosting have been identified. These drug candidates are in late lead optimization and we expect to nominate a clinical candidate in the near future. Phase 1 enabling nonclinical studies of this compound are planned to initiate in Q3 2022.

Merck Collaboration
Significant progress has been made in the nonalcoholic steatohepatitis (NASH) oligonucleotide research collaboration with Merck with respect to an initial undisclosed target, utilizing Aligos’ know-how and our proprietary oligonucleotide chemistry platform. In addition to advancing this program further into lead optimization, the achievements of this collaboration also resulted in Merck committing to an oligonucleotide research collaboration for a second undisclosed NASH target.

PD-L1 Small Molecule Inhibitors
We are also developing orally delivered, liver-targeted small molecule PD-L1 inhibitors in order to modulate host immune responses to hepatitis B virus (HBV). This approach has demonstrated favorable effects on HBsAg lowering in patients with CHB. A lead compound, ALG-093453, has been shown to induce T cell activation in an in vitro Jurkat T cell-NFAT assay with similar activity to the PD-1 monoclonal antibody (mAb), nivolumab. In addition, ALG-093453 induces HBV-antigen specific IFN-γ secretion from T cells from patients infected with HBV to a similar extent to nivolumab and the PD-L1 mAb, durvalumab.

Corporate:

NASH Related License & Collaboration Agreement
Aligos Expands Collaboration with Merck to Develop Oligonucleotide Therapies for NASH (Q1’22)

Under the original agreement, Merck and Aligos committed to applying Aligos’ oligonucleotide platform technology to discover, research, optimize and develop oligonucleotides directed against a certain undisclosed NASH target. That agreement has now been expanded to include the granting of a license to Merck of an early-stage program with respect to a second undisclosed NASH target on which Aligos has previously been working independently and separately from Merck. In addition, under this expanded arrangement, Merck has the ability to add to the collaboration a third target of interest with respect to the cardiometabolic/fibrosis space.
Financial Results for the Fourth Quarter and Full Year 2021

Cash, cash equivalents and investments totaled $205.8 million on December 31, 2021, compared with $243.5 million on December 31, 2020. With the discontinuation of the development of our STOPS drug candidate, ALG-010133, that was being explored to address CHB, together with the proceeds resulting from our partnering activities and other cost saving measures, we believe our December 31, 2021 cash balance provides sufficient cash to fund planned operations into the first half of 2024.

Net losses for the three months ended December 31, 2021 were $37.7 million or basic and diluted net loss per common share of $(0.89) compared to $34.4 million or basic and diluted net loss per common share of $(1.09) for the three months ended December 31, 2020. For the year ended December 31, 2021, Net losses were $128.3 million or basic and diluted net loss per common share of $(3.22) compared to $108.5 million or basic and diluted net loss per common share of $(10.87) for the year ended December 31, 2020.

Research and development (R&D) expenses for the three months ended December 31, 2021 were $28.6 million, compared with $28.1 million for the same period of 2020. The increase in R&D expenses for this comparative period is primarily related to increases in salaries and employee-related expenses. Total R&D stock-based compensation expense incurred for the three months ended December 31, 2021, was $1.9 million compared with $0.7 million for the same period for 2020. R&D expenses for the year ended December 31, 2021 were $104.2 million, compared with $79.9 million for the same period of 2020. The increase in R&D expenses for this comparative period is primarily attributable to increased expenses related to the Company’s continued development and manufacturing of ALG-000184, ALG-020572 clinical trial activities and remaining clinical and manufacturing expenses related to the discontinuation of ALG-010133 clinical program, as well as increases in salaries and employee-related expenses and preclinical programs. Total R&D stock-based compensation expense incurred in the year ended December 31, 2021, was $7.6 million, compared with $1.0 million for the same period of 2020.

General and administrative expenses for the three months ended December 31, 2021 were $9.7 million, compared to $6.2 million for the same periods of 2020 and for the year ended December 31, 2021 were $28.5 million, compared to $17.9 million for the same period of 2020. The increase in G&A expenses for both comparable periods is primarily attributable to higher employee-related costs associated with the growth of the Company’s operations and additional professional, legal and consulting services related to being a public company. Total G&A stock-based compensation expense incurred for the three months ended December 31, 2021 was $1.7 million compared with $0.6 million for the same period for 2020 and for the year ended December 31, 2021 was $5.9 million, compared with $1.9 million for the same period of 2020.

On March 10, 2022 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported financial and operating results for the fourth quarter and full year 2021 (Press release, Lineage Cell Therapeutics, MAR 10, 2022, View Source [SID1234609885]). Lineage management will host a conference call and webcast today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss its fourth quarter and full year 2021 financial and operating results and to provide a business update.

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"2021 was a transformative year for Lineage, in part because we entered into a worldwide corporate partnership with Roche and Genentech for our OpRegen program for the treatment of ocular disorders," stated Brian M. Culley, Lineage CEO. "We have continued to execute on our strategic plan to position Lineage as a leader in the allogeneic cell transplant revolution, supported by our regenerative medicine technology; manufacturing and differentiation of specific cell types. These cells are transplanted into the body to restore or improve function lost due to aging, injury, or disease. We believe the collaboration of our lead asset with a world-class pharmaceutical partner with extensive ophthalmology capabilities brings significant validation to our technology platform and our approach to product development. As importantly, this transaction adds significant new capital to help support the advancement of our OPC1 program, VAC platform, and the expansion of our regenerative medicine pipeline into new disease settings. Our corporate objectives in 2022 will be focused on the continued advancement of our current clinical programs and making responsible investments in the expansion of our novel approach to cell transplant medicine in disease settings where we believe we can make a meaningful impact. We look forward to announcing our new, internally developed pipeline candidate later this quarter."

Some of the more significant milestones we achieved in 2021 include:

– Established an exclusive worldwide collaboration and license agreement with Roche and Genentech (the "Roche Collaboration"), for the development and commercialization of OpRegen, a retinal pigment epithelium ("RPE") cell therapy, for the treatment of ocular disorders, including advanced dry age-related macular degeneration ("dry AMD") with geographic atrophy ("GA"), in a transaction worth up to $670 million in addition to double digit royalties;

– Reported a fourth case of retinal restoration with OpRegen; notably, four patients with dry AMD were observed to have areas of GA which diminished or remained unchanged relative to baseline for a period of at least 12 months;

– Announced a worldwide license agreement with Immunomic Therapeutics, Inc. for an allogeneic cell-based cancer immunotherapy based on our VAC platform; Lineage received $2 million upfront and may receive up to $67 million in development and commercial milestones plus royalties;

– Entered into an exclusive agreement with Neurgain Technologies to evaluate a novel delivery system for OPC1 to treat Spinal Cord Injury;

– Expanded our management team with the additions of Chief Financial Officer, Kevin L. Cook, as well as General Counsel, George A. Samuel, III; and

– Expanded our Board of Directors with the appointments of Drs. Anula Jayasuriya, M.D., Ph.D., M.B.A. and Dipti Amin, MBBS, FFPM, MRCGP, DCPSA, DCH, DRCOG, DGM.

Some of the events and milestones anticipated by Lineage in 2022 include:

– Announcement of a new pipeline program from our regenerative medicine cell therapy platform anticipated in March;

– Completion of GMP production of OPC1 via an improved and larger-scale manufacturing process and a new thaw-and-inject formulation; anticipated in Q1 2022;

– FDA interaction to discuss recent manufacturing improvements made to OPC1, anticipated in Q3 2022;

– Initiation of clinical performance and safety testing of the novel Parenchymal Spinal Delivery system device for OPC1, with an anticipated Investigational New Drug ("IND") amendment submission in Q3 2022;

– Updates from the ongoing VAC2 Phase 1 non-small cell lung cancer study; anticipated in Q2 2022;

– An anticipated IND submission for VAC2 in 2H 2022;

– Continued development of a cell-based therapeutic for glioblastoma with our strategic partner, Immunomic Therapeutics; ongoing throughout 2022;

– Evaluation of opportunities for new VAC product candidates based on internally identified or partnered tumor antigens; ongoing throughout 2022;

– Evaluation of partnership opportunities and expansion of existing collaborations; ongoing throughout 2022; and

– Continued participation in numerous investor and partnering meetings and medical and industry conferences to broaden the knowledge of our work.

Balance Sheet Highlights

Cash and cash equivalents totaled $55.7 million as of December 31, 2021. In January 2022, we received a $50.0 million upfront payment related to the Roche Collaboration and made subsequent payments pursuant to Lineage’s downstream obligations.

Fourth Quarter Operating Results

Revenues: Lineage’s revenue is generated primarily from research grants, royalties, and licensing fees. Total revenues for the three months ended December 31, 2021 were approximately $1.2 million, an increase of $0.8 million as compared to $0.4 million for the same period in 2020. The increase was related to royalties and licensing fees, which was primarily driven by licensing revenues in connection with collaboration agreements entered into in 2021.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A") expenses. Total operating expenses for the three months ended December 31, 2021 were $29.2 million, an increase of $23.1 million as compared to $6.1 million for the same period in 2020. The overall increase was substantially driven by $20.6 million in higher OpRegen-related expenses, mainly due to accruals for future financial obligations payable to the Israel Innovation Authority ("IIA") and Hadasit Medical Research Services and Development Ltd ("Hadasit"), related to the receipt of the $50.0 million upfront payment under the Roche Collaboration.

R&D Expenses: R&D expenses for the three months ended December 31, 2021 were $24.8 million, an increase of $22.2 million as compared to $2.6 million for the same period in 2020. The increase was substantially driven by the $21.0 million accrual for future financial obligations payable to IIA and Hadasit. Other drivers of the increased variance were related to $1.0 million and $0.6 million in higher expenses to support the development of the OPC1 and VAC programs, respectively.

G&A Expenses: G&A expenses for the three months ended December 31, 2021 were $4.4 million, an increase of $0.9 million as compared to $3.5 million for the same period in 2020. The increase was primarily attributable to increases of $0.3 million in legal and litigation expenses, $0.3 million in salaries and related benefits, and $0.3 million in share-based compensation expense.

Loss from Operations: Loss from operations for the three months ended December 31, 2021 was $28.2 million, an increase of $22.3 million as compared to $5.9 million for the same period in 2020, principally owing to collaboration-related expense accruals of $21.0 million which were not deferrable expenses, and as such, do not align with current period revenues due to revenue deferral accounting standards.

Other Income, Net: Other income, net for the three months ended December 31, 2021 was $0.2 million, compared to other income, net of $6.9 million for the same period in 2020. The variance was primarily related to changes in the value of marketable equity securities for the applicable periods.

Net Income/(Loss) Attributable to Lineage: The net loss attributable to Lineage for the three months ended December 31, 2021 was ($29.0) million, or ($0.17) per share (basic and diluted), compared to a net income attributable to Lineage of $2.0 million, or $0.01 per share (basic and diluted), for the same period in 2020. The large year-over-year change was principally due to the collaboration-related expense accruals amounting to ($0.12) per share which were not deferrable expenses, and as such, do not align with current period revenues due to revenue deferral accounting standards.

Full Year Operating Results

Revenues: Lineage’s revenue is generated primarily from research grants, royalties, and licensing fees. Total revenues for the year ended December 31, 2021 were $4.3 million, an increase of $2.5 million as compared to $1.8 million for the same period in 2020. The increase was primarily related to a $2.0 million increase in royalty revenues, and a $1.1 million increase in licensing revenues in connection with collaboration agreements, partially offset by a $0.6 million decrease in grant revenues.

Operating Expenses: Operating expenses are comprised of R&D expenses and G&A expenses. Total operating expenses for the year ended December 31, 2021 were $52.1 million, an increase of $24.2 million as compared to $27.9 million for the same period in 2020. The overall increase was substantially driven by $19.9 million in higher OpRegen-related expenses, mainly due to accruals for future financial obligations payable to IIA and Hadasit, related to the receipt of the $50.0 million upfront payment under the Roche Collaboration.

R&D Expenses: R&D expenses for the year ended December 31, 2021 were $33.9 million, an increase of $21.6 million as compared to $12.3 million for the same period in 2020. The increase was substantially driven by the $21.0 million accrual for future financial obligations payable to the IIA and Hadasit. Other drivers of the net increase variance were $2.2 million in higher manufacturing and device development costs to support the OPC1 program, offset by $0.3 million in lower VAC program expenses.

G&A Expenses: G&A expenses for the year ended December 31, 2021 were $18.2 million, an increase of approximately $2.6 million as compared to $15.6 million for the same period in 2020. The increase was primarily related to increases of $1.3 million in legal, litigation and patent expenses, $0.9 million in share-based compensation expenses, and $0.3 million in payroll and related benefits expense.

Loss from Operations: Loss from operations for the year ended December 31, 2021 was $49.2 million, an increase of $22.8 million as compared to $26.4 million for the same period in 2020, principally owing to collaboration-related expense accruals of $21.0 million which were not deferrable expenses, and as such, do not align with current period revenues due to revenue deferral accounting standards.

Other Income, Net: Other income, net for the year ended December 31, 2021 was $5.9 million, compared to other income, net of $4.5 million for the same period in 2020. The net variance was primarily related to the changes in the value of marketable equity securities for the applicable periods.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the year ended December 31, 2021 was $43.0 million, or $0.26 per share (basic and diluted), compared to a net loss attributable to Lineage of $20.6 million, or $0.14 per share (basic and diluted), for 2020. The large year-over-year change is principally due to collaboration-related expense accruals amounting to $0.13 per share which were not deferrable expenses, and as such, do not align with current period revenues due to revenue deferral accounting standards.

Conference Call and Webcast

Interested parties may access the conference call by dialing (866) 888-8633 from the U.S. and Canada and (636) 812-6629 from elsewhere outside the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through March 18, 2022, by dialing (855) 859-2056 from the U.S. and Canada and (404) 537-3406 from elsewhere outside the U.S. and Canada and entering conference ID number 7718167.