Aligos Therapeutics Inc

Previous wording

We are a clinical-stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver diseases and viral infections, including in the areas of metabolic dysfunction associated steatohepatitis (MASH), chronic hepatitis B (CHB) and coronavirus infections (e.g., SARS-CoV-2, SARS, MERS, and other related infections). The Aligos team has a demonstrated track record of success in drug development and medicinal chemistry in liver and viral diseases, resulting in three potential best-in-class drug candidates, all of which are currently in clinical studies.

Current wording

We are a clinical-stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver diseases and viral infections, including in the areas of metabolic dysfunction associated steatohepatitis (MASH), chronic hepatitis B (CHB) and coronavirus infections (e.g., SARS-CoV-2, SARS-CoV, MERS-CoV, and other related infections). The Aligos team has a demonstrated track record of success in drug development and medicinal chemistry in liver and viral diseases, resulting in three potential best-in-class drug candidates, all of which are currently in clinical studies.

Previous wording

Our pipeline of drug candidates includes ALG-055009 for MASH, ALG-000184 for CHB, ALG‑097558 for coronavirus, and we also have a portfolio of preclinical programs. ALG-055009 is our potential best-in-class thyroid hormone receptor beta (THR-β) agonist for MASH with enhanced pharmacologic properties vs. competitor THR-β agonists. Phase 1 data demonstrated linear PK with low variability, a well-tolerated safety profile, and expected thyromimetic effects. Phase 2a dosing with ALG-055009 began in April 2024 and topline data are expected in the fourth quarter of 2024. ALG-000184 is our potential best-/first-in-class CAM-E for CHB with enhanced pharmacologic properties vs. competitor CAM-E drugs and has demonstrated greater DNA suppression compared to the standard of care, nucleoside analogs (NAs), as well as multi-log reductions in viral antigens. Dosing with ALG-000184 is ongoing in 96-week Phase 1b cohorts with interim readouts expected throughout the year at upcoming scientific conferences.

Current wording

Our pipeline of drug candidates includes ALG-055009 for MASH, ALG-000184 for CHB, ALG‑097558 for coronavirus infections, and we also have a portfolio of preclinical programs. ALG-055009 is our potential best-in-class thyroid hormone receptor beta (THR-β) agonist for MASH with enhanced pharmacologic properties vs. competitor THR-β agonists. Phase 1 data demonstrated linear pharmacokinetics (PK) with low variability, a well-tolerated safety profile, and expected thyromimetic effects. Phase 2a enrollment was completed in May 2024 and topline data are expected in the early fourth quarter of 2024. ALG-000184 is our potential best-/first-in-class CAM-E for CHB with enhanced pharmacologic properties vs. competitor CAM-E drugs and has demonstrated greater HBV DNA suppression compared to the standard of care, nucleos(t)ide analogs (NAs), as well as multi-log 10 reductions in viral antigens. Dosing with ALG‑000184 is ongoing in 96-week Phase 1b cohorts with interim readouts expected throughout the year that will be presented at upcoming scientific conferences.

Previous wording

Our primary area of focus is MASH, a complex, chronic liver disease which is a leading cause of liver-related morbidity including cirrhosis, hepatocellular carcinoma, liver transplant, and end-stage liver disease. The FDA recently approved the first drug for MASH, resmetirom, a THR-β agonist, but a need remains for better therapies due to resmetirom’s sub-optimal risk-benefit profile, particularly its likely sub-maximal efficacy. To achieve this, we have purpose-built ALG-055009 to have increased potency (~50-fold greater vs. resmetirom in head-to-head in vitro studies) and ß selectivity as well as enhanced pharmacologic properties to deliver a better PK profile; all of these advantages make ALG-055009 well positioned to be a best-in-class THR-β agonist.

Current wording

Our primary area of focus is MASH, a complex, chronic liver disease which is a leading cause of liver-related morbidity including cirrhosis, hepatocellular carcinoma, liver transplant, and end-stage liver disease. The FDA recently approved the first drug for the treatment of MASH, resmetirom, a THR-β agonist, but a need remains for better therapies due to resmetirom’s sub-optimal risk-benefit profile, particularly its likely sub-maximal efficacy. To achieve this, we have purpose-built ALG-055009 to have increased potency (~50-fold greater vs. resmetirom in head-to-head in vitro studies) and ß selectivity as well as enhanced pharmacologic properties to deliver a better PK profile; we believe all of these advantages make ALG-055009 well positioned to be a potential best-in-class THR-β agonist.

Previous wording

ALG-055009 recently completed evaluation in a Phase 1 study in healthy volunteers (HVs) (oral single ascending doses (SAD)) and in subjects with hyperlipidemia (14 oral daily doses). Clinical data after single doses up to 4 mg and multiple doses up to 1 mg showed that ALG‑055009 was well tolerated, had dose proportional pharmacokinetics (PK) with low intersubject variability, and demonstrated expected thyromimetic effects (i.e., generally dose proportional increases in sex hormone binding globulin and decreases in various atherogenic lipids and thyroid hormones). In this same study, we have also evaluated relative bioavailability where we have shown the soft gelatin capsules being used in upcoming studies deliver similar exposures compared to the solution used in Phase 1 studies; we observed low intersubject PK variability and there was no evidence of a meaningful food effect. Based on these promising Phase 1 data, we have initiated the Phase 2a HERALD study (NCT06342947) at sites across the United States. The study is a 12-week randomized, placebo-controlled trial evaluating 4 doses (0.3 mg, 0.5 mg, 0.7 mg, and 0.9 mg) of ALG-055009 vs. placebo in approximately 100 subjects with presumed liver fibrosis at stages 1-3 (F1-F3) with MASH. In addition to collecting safety and PK data, this study is also designed to assess multiple efficacy biomarkers, which include MRI-PDFF and other non-invasive tests previously shown to be impacted by treatment with THR‑ß agonists. We anticipate sharing topline safety and 12 week MRI-PDFF data from this study in the fourth quarter of 2024.

Current wording

ALG-055009 completed evaluation in a Phase 1 study in healthy volunteers (HVs) (oral single ascending doses (SAD)) and in subjects with hyperlipidemia (14 oral daily doses). Clinical data after single doses up to 4 mg and multiple doses up to 1 mg showed that ALG‑055009 was well tolerated, had dose proportional PK with low intersubject variability, and demonstrated expected thyromimetic effects (i.e., generally dose proportional increases in sex hormone binding globulin and decreases in various atherogenic lipids and thyroid hormones). In this same study, we also evaluated relative bioavailability where we showed the soft gelatin capsules being used in current studies deliver similar exposures compared to the solution used in Phase 1 studies; we observed low intersubject PK variability and there was no evidence of a meaningful food effect. Based on these promising Phase 1 data, we initiated the Phase 2a HERALD study (NCT06342947) at sites across the United States. The study is a 12-week randomized, placebo-controlled trial evaluating 4 doses (0.3 mg, 0.5 mg, 0.7 mg, and 0.9 mg) of ALG-055009 vs. placebo in approximately 100 subjects with presumed liver fibrosis at stages 1-3 (F1-F3) with MASH. In addition to collecting safety and PK data, this study is also designed to assess multiple efficacy biomarkers, which include MRI-PDFF and other non-invasive tests previously shown to be impacted by treatment with THR‑ß agonists. We anticipate announcing topline safety and 12-week MRI-PDFF data from this study in the early fourth quarter of 2024.

Previous wording

In addition to our small molecule THR‑ß program, we are also progressing an oligonucleotide project for MASH through a collaboration with Merck. This program is currently progressing through preclinical activities.

Current wording

In addition to our small molecule THR‑ß program, we also have an oligonucleotide program for MASH, which is currently in the preclinical stage of development.

Previous wording

We have completed the initial Phase 1a study in healthy volunteers (HVs) for our CAM-E, ALG‑000184, and a Phase 1b dose ranging study evaluating the safety, PK and antiviral activity of 10-300 mg doses of ALG‑000184 for 28 days among untreated HBV e-antigen (HBeAg) positive/negative CHB subjects. For these studies, ALG‑000184 was found to be well tolerated with a favorable PK profile and demonstrated potentially best-in-class multi-log HBV DNA and RNA reductions at all doses tested, as well as HBV surface antigen (HBsAg) reductions in a subset of HBeAg positive subjects receiving 300 mg ALG‑000184 (Hou et. al, AASLD 2022). Based on the favorable profile after dosing up to 300 mg ALG‑000184 x 28 days, additional Phase 1b cohorts are currently ongoing and evaluating the risk-benefit profile of up to 300 mg doses of ALG‑000184 with or without entecavir (ETV) therapy for up to 96 weeks in HBeAg positive/negative CHB subjects. Preliminary data have been presented for several of these cohorts (Hou et al., APASL 2024, Yuen et al., APASL 2024) and indicate that ALG‑000184 dosed for up to 64 weeks was well tolerated with a favorable PK profile and potentially best-in-class antiviral activity. Specifically, antiviral activity data in subjects dosed with 300 mg ALG‑000184 + ETV for up to 64 weeks are available in 2 cohorts of HBeAg positive subjects with normal/elevated baseline ALT. In these cohorts, we observed mean DNA reductions of ~7 log 10 IU/mL. Notably, subjects in these cohorts who initially received ETV monotherapy x 12 weeks had more modest reductions in HBV DNA as compared to subjects receiving ALG‑000184 + ETV over the same time period. In addition, subjects initially receiving ETV only then experienced further reductions in HBV DNA levels once they started receiving the combination of ETV and ALG‑000184, and their HBV DNA levels also reached levels exceeding 6 log 10 IU/mL, indicating an additive antiviral effect of ALG-000184 with ETV. Further, subjects receiving 300 mg ALG‑000184 monotherapy had similar DNA reductions as subjects receiving 300 mg ALG‑000184 + ETV and no subject has experienced viral breakthrough. These observations indicate ETV is not meaningfully contributing to observed antiviral activity and there is no evidence of emergence of resistance after dosing with ALG‑000184 monotherapy for up to 64 weeks, the last time point studied to date. We have also observed in subjects dosed with either 100 or 300 mg of ALG-000184 + ETV that mean blood levels of all the three major viral antigens (HBsAg, HBeAg, and HBV core-related antigen (HBcrAg)) all declined by ~1-2 log 10 units and these declines were dose related. By comparison, no meaningful change in any of these antigen levels was observed in subjects dosed with ETV alone. Compared to earlier studies with the current standard of care NA, tenofovir (Buti et al., Lancet Gastro, 2016), these Phase 1b data indicate our CAM‑E ALG‑000184 may achieve a substantially higher proportion of …

Excerpt shortened here; the source contains the full paragraph.

Current wording

We have completed the initial Phase 1a study in HVs for our CAM-E, ALG‑000184, and a Phase 1b dose ranging study evaluating the safety, PK and antiviral activity of 10-300 mg doses of ALG‑000184 for 28 days among untreated HBV e-antigen

Previous wording

We are also exploring ways to boost immune responses via small molecule inhibitors of the Programmed Cell Death Ligand 1 (PD-L1) transmembrane protein and its interaction with Programmed Cell Death Protein 1 (PD-1). We have rationally designed these T cell activating drug candidates to partition preferentially to the liver and thereby potentially mitigate systemic toxicity in an effort to develop better tolerated PD-1/PD-L1 inhibitors for CHB patients. Lead molecules developed to date show similar in vivo efficacy in tumor models to approved PD-1/PD-L1 antibodies. Our small molecule lead compounds also demonstrate greater PD-L1 target occupancy at a lower dose in a humanized PD-L1 subcutaneous tumor model compared to competitor small molecule PD-L1 inhibitors. We have recently selected two lead molecules and have completed scale-up to enable further advancement towards clinical development.

Current wording

We are also exploring ways to boost immune responses via small molecule inhibitors of the Programmed Cell Death Ligand 1 (PD-L1) transmembrane protein and its interaction with Programmed Cell Death Protein 1 (PD-1). We have rationally designed these T cell activating drug candidates to partition preferentially to the liver and thereby potentially mitigate systemic toxicity with the goal to develop better tolerated PD-1/PD-L1 inhibitors for CHB patients. Lead molecules developed to date show similar in vivo efficacy in tumor models to approved PD-1/PD-L1 antibodies. Our small molecule lead compounds also demonstrate greater PD-L1 target occupancy at a lower dose in a humanized PD-L1 subcutaneous tumor model compared to competitor small molecule PD-L1 inhibitors. We have recently selected two lead molecules and have completed scale-up to enable further advancement towards clinical development.

Previous wording

ALG‑097558 has been shown to be at least 6-fold more potent than nirmatrelvir and other PIs in clinical development against a panel of SARS-CoV-2 variants (including Omicron). It also has demonstrated broad pan-coronavirus activity, including against SARS and MERS. Single doses up to 2000 mg and multiple doses up to 800 mg Q12 for 7 days have been well tolerated with an acceptable PK profile that indicates ritonavir boosting is not required. Based on these Phase 1 data (Wilkes et al, ESCMID, 2024), the projected efficacious dose range to treat SARS-CoV-2 is 200-600 mg ALG-097558 Q12 x 5 days. Future development of ALG-097558, including ongoing Phase 2 enabling activities, will be funded by external sources, including public funding sources as described below.

Current wording

ALG‑097558 has been shown to be at least 6-fold more potent than nirmatrelvir and other PIs in clinical development against a panel of SARS-CoV-2 variants (including Omicron). It also has demonstrated broad pan-coronavirus activity, including against SARS-CoV and MERS-CoV. Single doses up to 2000 mg and multiple doses up to 800 mg Q12 for 7 days have been well tolerated with an acceptable PK profile that indicates ritonavir boosting is not required. Based on these Phase 1 data (Wilkes et al, ESCMID, 2024), the projected efficacious dose range to treat SARS-CoV-2 is 200-600 mg ALG-097558 Q12 x 5 days. Future development of ALG-097558, including ongoing Phase 2 enabling activities, will be funded by external sources, including public funding sources as described below.

Previous wording

Preclinical activities for our coronavirus program were partially funded through a grant from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern program through the Metropolitan AntiViral Drug Accelerator (MAVDA) consortium. Specific clinical and nonclinical studies for the ALG-097558 program and the follow up compound, are now also being funded with federal funds from the NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93023C00052. We plan to conduct the clinical pharmacology studies in the second half of 2024 through the end of 2025 as part of this NIAID contract. We expect to receive approximately $12.3 million in funds across these two NIH awards and contracts to support these activities. We are also presently seeking additional external funding (e.g., from governmental agencies) to support future studies (e.g., Phase 2) as we advance ALG-097558 for the treatment of COVID-19 and future coronavirus pandemics.

Current wording

Preclinical activities for our coronavirus program were partially funded through a grant from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern program through the Metropolitan AntiViral Drug Accelerator (MAVDA) consortium. Specific clinical and nonclinical studies for the ALG-097558 program and the follow up compound, are now also being funded with federal funds from the NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93023C00052. We filed an IND in the third quarter of 2024 and clinical studies in special populations are planned to be initiated in the second half of 2024 through the end of 2025 as part of this NIAID contract. We expect to receive approximately $13.8 million in funds across these two NIH awards and contracts to support these activities. We are also presently seeking additional external funding (e.g., from governmental agencies) to support future studies (e.g., Phase 2) as we advance ALG-097558 for the treatment of COVID-19 and future coronavirus pandemics.

Previous wording

We have incurred net losses and negative cash flows from operations in each year since our formation in February 2018. Our net losses were $34.9 million and $23.0 million for the three months ended March 31, 2024 and 2023, respectively, and our net losses were $87.7 million for the year ended December 31, 2023. We have had no revenue from product sales. As of March 31, 2024, we had an accumulated deficit of $521.7 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses over at least the next several years. Our net operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of our clinical trials and nonclinical studies and our other research and development expenses. We have no internal manufacturing capabilities or sales force and outsource a substantial portion of our clinical trial work to third parties.

Current wording

We have incurred net losses and negative cash flows from operations in each year since our formation in February 2018. Our net losses were $29.8 million and $41.7 million for the six months ended June 30, 2024 and 2023, respectively, and our net losses were $87.7 million for the year ended December 31, 2023. We have had no revenue from product sales. As of June 30, 2024, we had an accumulated deficit of $516.6 million. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant expenses and increasing operating losses over at least the next several years. Our net operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of our clinical trials and nonclinical studies and our other research and development expenses. We have no internal manufacturing capabilities or sales force and outsource a substantial portion of our clinical trial work to third parties.

Previous wording

Interest and other income (expense), net comprises interest income, net and other income (expense), net. Interest income, net primarily consists of interest earned on our cash, cash equivalents, and investments. Other income (expense), net consists primarily of the change in fair value of our investments, common warrant liability and foreign currency gains/losses.

Current wording

Interest and other income, net comprises interest income, net and other income, net. Interest income, net primarily consists of interest earned on our cash, cash equivalents, and investments. Other income, net consists primarily of the change in fair value of our common warrant liability, investments and foreign currency gains/losses.

Previous wording

Comparison of the three months ended March 31, 2024 and 2023

Current wording

Comparison of the three and six months ended June 30, 2024 and 2023

Previous wording

The following table summarizes our operating expenses for the three months ended March 31, 2024 and 2023 (in thousands):

Current wording

The following table summarizes our operating expenses for the three and six months ended June 30, 2024 and 2023 (in thousands):

Previous wording

Revenue from collaborations decreased by $2.3 million during the three months ended March 31, 2024, compared to the same period in 2023. The decrease was primarily due to the completion of the Amended Agreement with Merck in the first quarter of 2024.

Current wording

Revenue from collaborations decreased by $2.6 million and $4.9 million, respectively, for the three and six months ended June 30, 2024, when compared to the same period in 2023. The decrease was primarily due to the completion of the Amended Agreement with Merck in the first quarter of 2024.

Previous wording

Research and development expenses decreased by $1.8 million during the three months ended March 31, 2024, compared to the same period in 2023. The decrease in the three-month period was primarily due to a $2.0 million decrease in employee-related costs including a $0.8 million decrease in stock-based compensation, and a $0.1 million decrease in depreciation. This was partially offset by a $0.1 million increase in third party expenses and an increase of $0.2 million in facility and other expenses.

Current wording

Research and development expenses increased by $2.5 million during the six months ended June 30, 2024, compared to the same period in 2023. The increase in the six-month period was primarily due to a $6.5 million increase in third party expenses due to increased clinical study costs. This was partially offset by a $2.8 million decrease in employee-related costs including a $1.1 million decrease in stock-based compensation, a $0.1 million decrease in depreciation, and a decrease of $1.0 million in facility and other expenses.

Previous wording

General and administrative expenses decreased by $1.8 million during the three months ended March 31, 2024, compared to the same period in 2023. This was primarily due to a $1.3 million decrease in third party expenses due to reduced legal and IP spend, a $0.3 million decrease in facility and other expenses, and a $0.2 million decrease in employee-related costs.

Current wording

General and administrative expenses decreased by $2.9 million during the three months ended June 30, 2024, compared to the same period in 2023. This was primarily due to a $1.6 million decrease in third party expenses due to reduced legal and IP spend, a $0.2 million decrease in facility and other expenses, and a $1.0 million decrease in employee-related costs.

Previous wording

The following table summarizes our interest and other income (expense), net for the three months ended March 31, 2024 and 2023 (in thousands):

Current wording

The following table summarizes our interest and other income, net for the three and six months ended June 30, 2024 and 2023 (in thousands):

Previous wording

Interest income, net decreased by $0.2 million for the three months ended March 31, 2024 compared to the three months ended March 31, 2023, primarily due to a general decrease in market interest rates.

Current wording

Interest income, net decreased by $0.6 million and $0.8 million for the three and six months ended June 30, 2024 when compared to the same periods ended June 30, 2023, primarily due to a general decrease in market interest rates.

Previous wording

Other income (expense), net decreased for the three months ended March 31, 2024 compared to the three months ended March 31, 2023, due primarily to the change in fair value of the Common Warrants associated with the Securities Purchase Agreement.

Current wording

Other income, net increased by $31.2 million and $17.6 million, respectively, for the three and six months ended June 30, 2024 compared to the same periods ended June 30, 2023, due to the change in fair value of the Common Warrants associated with the Securities Purchase Agreement which are remeasured at the end of each reporting period.

Previous wording

We have incurred net losses since inception. We have not generated any revenue from product sales or any other sources and have incurred significant operating losses. We have not yet commercialized any products and we do not expect to generate revenue from sales of any drug candidates for at least several years, if ever.

Current wording

We have incurred net losses in each year since inception. We have not generated any revenue from product sales or any other sources and have incurred significant operating losses. We have not yet commercialized any products and we do not expect to generate revenue from sales of any drug candidates for at least several years, if ever.

Previous wording

Our operations have been financed primarily by net proceeds from the sale and issuance of our convertible preferred stock, net proceeds from our IPO, proceeds from public offerings, and proceeds from private placements of our common stock, warrants and pre-funded warrants, and the issuance of convertible debt.

Current wording

Our operations have been financed primarily by net proceeds from the sale and issuance of our convertible preferred stock, proceeds from public offerings, revenue from customer and collaboration agreements, and proceeds from private placements of our common stock, warrants and pre-funded warrants, and the issuance of convertible debt.

Previous wording

As of March 31, 2024, we had cash, cash equivalents and investments of $112.7 million. This includes the net proceeds of $86.2 million from our private placement in October 2023.

Current wording

As of June 30, 2024, we had cash, cash equivalents and investments of $94.5 million.

Previous wording

During the three months ended March 31, 2024, operating activities utilized $22.7 million of cash, primarily resulting from our net loss of $34.9 million and net changes in operating assets and liabilities of $5.5 million, partially offset by non-cash charges of $17.6 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $5.5 million, consisting of a decrease of $4.8 million in accrued liabilities, a decrease of $0.6 million in operating lease liabilities, a decrease of $0.1 million in deferred revenue from collaborations, and a decrease of $0.5 million in deferred revenue from customers, partially offset by a decrease in other assets of $0.2 million and an increase of $0.3 million in accounts payable. The decrease in deferred revenue from collaborations was due to the recognition of revenue from collaborations due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to the bonus payment that occurred in the first quarter of 2024. The decrease in accounts payable is due to the timing of payments to vendors.

Current wording

During the six months ended June 30, 2024, operating activities utilized $42.2 million of cash, primarily resulting from our net loss of $29.8 million and net changes in operating assets and liabilities of $1.4 million, partially offset by non-cash charges of $11.1 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $1.4 million, consisting of a decrease of $4.8 million in accrued liabilities, a decrease of $1.3 million in operating lease liabilities, a decrease of $0.1 million in deferred revenue from collaborations, an increase of $0.1 million in deferred revenue from customers, and a decrease in other assets of $0.3 million, partially offset by an increase of $4.3 million in accounts payable. The decrease in deferred revenue from collaborations was due to the recognition of revenue from collaborations due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to the bonus payments that occurred in the first quarter of 2024. The decrease in accounts payable is due to the timing of payments to vendors.

Previous wording

During the three months ended March 31, 2023, operating activities utilized $22.4 million of cash, primarily resulting from our net loss of $23.0 million and net changes in operating assets and liabilities of $3.7 million, partially offset by non-cash charges of $4.2 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $3.7 million, consisting of a decrease of $1.9 million in accounts payable, a decrease of $0.9 million in accrued liabilities, a decrease of $0.7 million in operating lease liabilities, and a decrease of $2.3 million in deferred revenue from collaborations and customer, partially offset by a decrease in other assets of $2.1 million. The decrease in deferred revenue from collaborations and customers was due to the recognition of revenue from collaborations and customers due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to charges related to the discontinuation of our ASO and STOPs drug candidates. The decrease in accounts payable is due to the timing of payments to vendors.

Current wording

During the six months ended June 30, 2023, operating activities utilized $36.0 million of cash, primarily resulting from our net loss of $41.7 million and net changes in operating assets and liabilities of $3.0 million, partially offset by non-cash charges of $8.8 million. Net cash used in operating activities resulted in changes in our operating assets and liabilities of $3.0 million, consisting of a decrease of $1.5 million in accounts payable, a decrease of $2.2 million in accrued liabilities, a decrease of $1.2 million in operating lease liabilities, and a decrease of $4.6 million in deferred revenue from collaborations, partially offset by a decrease in other assets of $4.3 million and an increase of $2.2 million in deferred revenue from customers. The decrease in deferred revenue from collaborations was due to the recognition of revenue from collaborations due to progress towards the completion of the projects. The decrease in accrued liabilities was largely due to charges related to the discontinuation of our ASO and STOPs drug candidates. The decrease in accounts payable is due to the timing of payments to vendors.

Previous wording

During the three months ended March 31, 2024, investing activities provided $88.6 million of cash, primarily due to $88.6 million of purchase of short-term investments.

Current wording

During the six months ended June 30, 2024, investing activities used $48.6 million of cash, primarily due to $88.6 million of purchase of short-term investments partially offset by $40.0 million related to maturities of short-term investments.

Previous wording

During the three months ended March 31, 2023, investing activities provided $20.0 million of cash, primarily due to $20.0 million of investment maturities.

Current wording

During the six months ended June 30, 2023, investing activities provided $45.0 million of cash, primarily due to $45.0 million of investment maturities.

Previous wording

During the three months ended March 31, 2024, net cash used in financing activities was $19 thousand, consisting primarily due to payments of our finance leases.

Current wording

During the six months ended June 30, 2024, net cash provided by financing activities was $262.0 thousand, consisting primarily due to proceeds from the ESPP purchase.

Previous wording

During the three months ended March 31, 2023, net cash utilized by financing activities was $1 thousand, consisting primarily of payments of our finance leases, partially offset by proceeds from the exercise of stock option.

Current wording

During the six months ended June 30, 2023, net cash provided by financing activities was $413.0 thousand, consisting primarily of proceeds from the ESPP purchase and from the exercise of stock options, partially offset by payments of our finance leases.