Trevi Therapeutics Inc

Previous wording

Haduvio is an oral extended-release formulation of nalbuphine. Nalbuphine is a mixed κ-opioid receptor agonist and μ-opioid receptor antagonist that has been approved and marketed as an injectable for pain indications for more than 30 years in the United States, or the U.S., and Europe. The κ- and μ-opioid receptors are known to be critical mediators of cough. Nalbuphine’s mechanism of action also mitigates the risk of abuse associated with μ-opioid agonists because it antagonizes, or blocks, the μ-opioid receptor. Parenteral nalbuphine is not scheduled as a controlled substance in the U.S. and most of Europe.

Current wording

We are a clinical-stage biopharmaceutical company focused on the development and commercialization of the investigational therapy Haduvio (oral nalbuphine ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis, or IPF, and refractory chronic cough, or RCC. Haduvio is an oral extended-release formulation of nalbuphine. Haduvio acts on the cough reflex arc both centrally and peripherally as a kappa agonist and a mu antagonist (KAMA). Kappa and mu are opioid receptors that play a key role in controlling cough hypersensitivity. Nalbuphine is a mixed kappa-opioid receptor agonist and mu-opioid receptor antagonist that has been approved and marketed as an injectable for pain indications for more than 30 years in the United States, or the U.S., and Europe. Nalbuphine’s mechanism of action also mitigates the risk of abuse associated with mu-opioid agonists because it antagonizes, or blocks, the mu-opioid receptor. Parenteral nalbuphine is not scheduled as a controlled substance in the U.S. and most of Europe.

Previous wording

In December 2023, we initiated our Phase 2b CORAL clinical trial, which is a dose-ranging study evaluating the efficacy, safety and tolerability of Haduvio for chronic cough in IPF. This trial is expected to be conducted at multiple sites in up to 11 countries and uses a randomized, double-blind, placebo-controlled, parallel-arm design, which evaluates three doses of Haduvio over six weeks as compared to placebo. The primary efficacy endpoint for the trial is the relative change in 24-hour cough frequency at the end of week six versus baseline for Haduvio compared to placebo, as measured via an objective cough monitor. We expect the trial to enroll approximately 160 patients. The protocol for the Phase 2b CORAL clinical trial provides for a sample size re-estimation, or SSRE, analysis once approximately 50% of the patients in the trial are evaluable for the primary endpoint. The SSRE is expected to occur in the fourth quarter of 2024, and topline data from the full trial are expected to be available in the first half of 2025 assuming there are no adjustments made to the sample size.

Current wording

We are conducting our Phase 2b CORAL clinical trial, which is a dose-ranging study evaluating the efficacy, safety and tolerability of Haduvio for chronic cough in IPF. This trial is being conducted at multiple sites in ten countries and uses a randomized, double-blind, placebo-controlled, parallel-arm design, which evaluates three doses of Haduvio over six weeks as compared to placebo. The primary efficacy endpoint for the trial is the relative change in 24-hour cough frequency at the end of week six versus baseline for Haduvio compared to placebo, as measured via an objective cough monitor. We expect the trial to enroll approximately 160 patients. The protocol for the Phase 2b CORAL clinical trial provides for a sample size re-estimation, or SSRE, analysis once approximately 50% of the patients in the trial are evaluable for the primary endpoint. In October 2024, we reached 50% of the targeted study enrollment. As a result, we expect the SSRE analysis will be performed once the last of these patients completes the six weeks of treatment and is evaluable for the primary endpoint. The outcome of the SSRE analysis is expected in December 2024 and is expected to result in the recommendation to: maintain the current targeted sample size of 160 patients, upsize the targeted sample size within a pre-specified range, or evaluate for futility. Assuming no adjustments are made to the sample size, we expect to report topline results in the first half of 2025.

Previous wording

We are conducting our Phase 1b respiratory physiology study, which we refer to as TIDAL, in the United Kingdom and U.S. and we have initiated screening. The study will evaluate the effect of Haduvio on respiratory physiology in patients with IPF of varying disease severity. TIDAL is a randomized, single-blind, placebo-controlled study. We expect to enroll approximately 25 patients who will be in-patient for 10 days. The primary endpoint of the study is the effect of escalating doses of Haduvio on respiratory function, as measured by minute ventilation. Secondary endpoints of additional respiratory functions will also be measured. The goal of this study is to define the patient population for any Phase 3 studies that we may conduct in chronic cough in IPF.

Current wording

We are also conducting a Phase 1b respiratory physiology study, which we refer to as TIDAL, in the United Kingdom and U.S. and we have initiated screening. The study will evaluate the effect of Haduvio on respiratory physiology in patients with IPF of varying disease severity. TIDAL is a randomized, single-blind, placebo-controlled study. We expect to enroll up to approximately 25 patients who will be in-patient for ten days. The primary endpoint of the study is the effect of escalating doses of Haduvio on respiratory function, as measured by minute ventilation. Secondary endpoints of additional respiratory functions will also be measured. The goal of this study is to define the patient population for any Phase 3 studies that we may conduct in chronic cough in IPF.

Previous wording

RCC Program. We are also developing Haduvio for the treatment of RCC. In November 2023, we initiated our Phase 2a clinical trial of Haduvio for RCC, which we refer to as the Phase 2a RIVER trial. The Phase 2a RIVER trial is a randomized, double-blind, placebo-controlled, two-treatment, two-period, crossover study that is designed to evaluate the efficacy, safety, tolerability and dosing of Haduvio for the treatment of RCC. We are conducting this trial at multiple sites in the United Kingdom and Canada. The trial was designed to enroll approximately 60 adult patients. The primary endpoint of the trial is a mean change in 24-hour cough frequency in the overall population as determined using an objective cough monitor. Patients are randomized with a 1:1 stratification between those with 10-19 coughs/hour (moderate 24-hour cough frequency) and those with at least 20 coughs/hour (high 24-hour cough frequency). The trial will also explore secondary endpoints, including patient reported outcome measures for cough frequency and severity. The study is now approximately 80% enrolled and we expect to report topline efficacy and safety data in the fourth quarter of 2024.

Current wording

RCC Program. We are also developing Haduvio for the treatment of RCC. We are conducting a Phase 2a clinical trial of Haduvio for RCC, which we refer to as the Phase 2a RIVER trial. The Phase 2a RIVER trial is a randomized, double-blind, placebo-controlled, two-treatment, two-period, crossover study that is designed to evaluate the efficacy, safety, tolerability and dosing of Haduvio for the treatment of RCC. We are conducting this trial at multiple sites in the United Kingdom and Canada. The primary endpoint of the trial is a mean change in 24-hour cough frequency in the overall population as determined using an objective cough monitor. Based on the screening results, the trial enrolled patients into one of two subgroups: 10-19 coughs/hour (moderate 24-hour cough frequency) and ≥20 coughs/hour (high 24-hour cough frequency). The trial will explore secondary endpoints, including patient reported outcome measures for cough frequency and severity. The trial was designed to enroll approximately 60 adult patients. In October 2024, we announced that we had completed enrollment of this trial. We expect to report topline efficacy and safety data in the first quarter of 2025.

Previous wording

Human Abuse Potential. We initiated a human abuse potential, or HAP, study in the fourth quarter of 2022 to compare the abuse potential of oral nalbuphine to intravenous, or IV, butorphanol. The parenteral version of nalbuphine is currently unscheduled in the U.S. by the Drug Enforcement Agency. The study is a randomized, double-blind, active and placebo-controlled five-way crossover study. The study is being conducted in two parts. The first part of the study characterized various IV butorphanol doses in order to select a dose to be studied and has been completed. The U.S. Food and Drug Administration, or FDA, requested that we submit the data from the first part of the study in support of our IV butorphanol dose selection for review and comment prior to commencing the second part of the study. We submitted the data to the FDA and the FDA agreed to the selected dose of IV butorphanol. In the second part of the study, we are comparing the likeability of oral nalbuphine with the selected dose of IV butorphanol using various drug-liking scales, including the primary endpoint, which measures the peak effect for drug liking assessed using a visual analog scale. We are also evaluating safety and physiological measures, pharmacokinetic data, and abuse-related adverse events. We initiated dosing in the second part of the study in January 2024 and the study is approximately 95% enrolled. We expect to complete enrollment in the third quarter of 2024 and report topline data from the study in the fourth quarter of 2024.

Current wording

Human Abuse Potential. We are conducting a human abuse potential, or HAP, study to compare the abuse potential of oral nalbuphine to intravenous, or IV, butorphanol. The parenteral version of nalbuphine is currently unscheduled in the U.S. by the Drug Enforcement Agency. The study is a randomized, double-blind, active and placebo-controlled five-way crossover study. The study is being conducted in two parts. The first part of the study characterized various IV butorphanol doses in order to select a dose to be studied and has been completed. The U.S. Food and Drug Administration, or FDA, requested that we submit the data from the first part of the study in support of our IV butorphanol dose selection for review and comment prior to commencing the second part of the study. We submitted the data to the FDA and the FDA agreed to the selected dose of IV butorphanol. In the second part of the study, we are comparing the likeability of oral nalbuphine with the selected dose of IV butorphanol using various drug-liking scales, including the primary endpoint, which measures the peak effect for drug liking assessed using a visual analog scale. We are also evaluating safety and physiological measures, pharmacokinetic data, and abuse-related adverse events. The second part of the study is fully enrolled and dosing is complete. We expect to report topline data from the study in December 2024.

Previous wording

We expect that we will need to conduct an additional Phase 3 clinical trial to support the submission of a new drug application to the FDA, a marketing authorization application, or MAA, to the European Medicines Agency and an MAA to the Medicines and Healthcare Products Regulatory Agency in the United Kingdom for Haduvio for the treatment of prurigo nodularis, and we plan to request an end of Phase 2 meeting with the FDA. Following discussions with the FDA and other regulatory authorities, we plan to determine next steps with respect to our prurigo nodularis program, including with respect to the conduct of any future Phase 3 clinical trial. We do not intend to complete the development of Haduvio for this indication ourselves, and may seek to enter into a strategic collaboration for the continued development of this program.

Current wording

We expect that we will need to conduct an additional Phase 3 clinical trial to support the submission of a new drug application to the FDA, a marketing authorization application, or MAA, to the European Medicines Agency and an MAA to the Medicines and Healthcare Products Regulatory Agency in the United Kingdom for Haduvio for the treatment of prurigo nodularis. Following discussions with the FDA and other regulatory authorities, we plan to determine next steps with respect to our prurigo nodularis program, including with respect to the conduct of any future Phase 3 clinical trial. We do not intend to complete the development of Haduvio for this indication ourselves, and may seek to enter into a strategic collaboration for the continued development of this program.

Previous wording

Since commencing operations in 2011, we have devoted substantially all of our efforts and financial resources to the clinical development of Haduvio. We have not generated any revenue from product sales and, as a result, we have never been profitable and have incurred net losses in each year since commencement of our operations. As of June 30, 2024, we had an accumulated deficit of $262.4 million, primarily as a result of research and development and general and administrative expenses. We do not expect to generate product revenue unless and until we obtain marketing approval for and commercialize Haduvio for the treatment of chronic cough in IPF and RCC or for the treatment of prurigo nodularis and we can provide no assurance that we will ever generate significant revenue or profits.

Current wording

Since commencing operations in 2011, we have devoted substantially all of our efforts and financial resources to the clinical development of Haduvio. We have not generated any revenue from product sales and, as a result, we have never been profitable and have incurred net losses in each year since commencement of our operations. As of September 30, 2024, we had an accumulated deficit of $275.6 million, primarily as a result of research and development and general and administrative expenses. We do not expect to generate product revenue unless and until we obtain marketing approval for and commercialize Haduvio for the treatment of chronic cough in IPF and RCC or for the treatment of prurigo nodularis and we can provide no assurance that we will ever generate significant revenue or profits.

Previous wording

In June 2023, we filed with the SEC a universal shelf registration statement on Form S-3, or the Shelf Registration Statement, which allows us to offer and sell up to $200.0 million of common stock, preferred stock, debt securities, units and/or warrants from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale. The Shelf Registration Statement was filed to replace our prior universal shelf registration statement on Form S-3 and was declared effective on August 15, 2023. Further, in June 2023, we entered into a new sales agreement with Leerink Partners, LLC (formerly SVB Securities), or Leerink Partners, which we refer to as the 2023 ATM Sales Agreement, under which we may issue and sell shares of common stock, from time to time by any method that is deemed an “at-the-market” offering as defined in Rule 415(a)(4) under the Securities Act. We are not obligated to make any sales of our common stock under the 2023 ATM Sales Agreement. We filed a prospectus under the Shelf Registration Statement for the offer and sale of shares of our common stock having an aggregate offering price of up to $75.0 million pursuant to the 2023 ATM Sales Agreement. In accordance with the terms of the 2023 ATM Sales Agreement, the ATM Sales Agreement terminated upon effectiveness of the Shelf Registration Statement, at which point we were no longer able to issue and sell shares of our common stock under the ATM Sales Agreement. As of June 30, 2024, we had issued and sold 1,474,926 shares of common stock for gross proceeds of $5.0 million, before deducting estimated commissions and allocated fees of $0.2 million under the 2023 ATM Sales Agreement.

Current wording

In June 2023, we filed with the SEC a universal shelf registration statement on Form S-3, or the Shelf Registration Statement, which allows us to offer and sell up to $200.0 million of common stock, preferred stock, debt securities, units and/or warrants from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale. The Shelf Registration Statement was filed to replace our prior universal shelf registration statement on Form S-3 and was declared effective on August 15, 2023. Further, in June 2023, we entered into a new sales agreement with Leerink Partners, LLC (formerly SVB Securities), or Leerink Partners, which we refer to as the 2023 ATM Sales Agreement, under which we may issue and sell shares of common stock, from time to time by any method that is deemed an “at-the-market” offering as defined in Rule 415(a)(4) under the Securities Act. We are not obligated to make any sales of our common stock under the 2023 ATM Sales Agreement. We filed a prospectus under the Shelf Registration Statement for the offer and sale of shares of our common stock having an aggregate offering price of up to $75.0 million pursuant to the 2023 ATM Sales Agreement. In accordance with the terms of the 2023 ATM Sales Agreement, the ATM Sales Agreement terminated upon effectiveness of the Shelf Registration Statement, at which point we were no longer able to issue and sell shares of our common stock under the ATM Sales Agreement. As of September 30, 2024, we had issued and sold 3,086,729 shares of common stock for gross proceeds of $10.0 million, before deducting estimated commissions and allocated fees of $0.3 million under the 2023 ATM Sales Agreement. Subsequent to September 30, 2024, and through October 31, 2024, we issued and sold 1,411,336 shares of common stock for gross proceeds of $4.6 million, before deducting estimated commissions and allocated fees of $0.1 million under the 2023 ATM Sales Agreement.

Previous wording

On October 5, 2021 and October 18, 2021, we issued and sold in two private placements, or the October 2021 Private Placements, in the aggregate (i) 4,225,053 shares of our common stock and accompanying warrants to purchase an aggregate of 8,450,106 shares of our common stock, and (ii) pre-funded warrants to purchase up to an aggregate of 4,926,069 shares of our common stock and accompanying warrants to purchase an aggregate of 9,852,138 shares of our common stock. Each share of our common stock and accompanying common stock warrants were sold together at a combined price of $1.62, and each pre-funded warrant and accompanying common stock warrants were sold together at a combined price of $1.619, for gross proceeds of approximately $14.8 million. Each pre-funded warrant had an exercise price of $0.001 per share, became exercisable immediately upon issuance and continued to be exercisable until exercised in full. The accompanying common stock warrants have an exercise price of $1.37 per share and became exercisable immediately upon issuance. Of the accompanying common stock warrants, warrants to purchase an aggregate of 7,299,270 shares had an expiration date of April 5, 2025, warrants to purchase an aggregate of 1,851,852 shares had an expiration date of April 18, 2025, warrants to purchase an aggregate of 7,299,270 shares had an expiration date of October 5, 2028, and warrants to purchase an aggregate of 1,851,852 shares had an expiration date of October 18, 2028. As of July 31, 2024, all of the pre-funded warrants have been exercised, all of the accompanying common stock warrants expiring on April 5, 2025 have been exercised, and accompanying common stock warrants to purchase 1,299,270 shares expiring on October 5, 2028 have been exercised. Warrants to purchase 1,851,852 shares of common stock that are to expire on April 18, 2025, warrants to purchase 6,000,000 shares of common stock that are to expire on October 5, 2028 and warrants to purchase 1,851,852 shares of common stock that are to expire on October 18, 2028 remained outstanding.

Current wording

On October 5, 2021 and October 18, 2021, we issued and sold in two private placements, or the October 2021 Private Placements, in the aggregate (i) 4,225,053 shares of our common stock and accompanying warrants to purchase an aggregate of 8,450,106 shares of our common stock, and (ii) pre-funded warrants to purchase up to an aggregate of 4,926,069 shares of our common stock and accompanying warrants to purchase an aggregate of 9,852,138 shares of our common stock. Each share of our common stock and accompanying common stock warrants were sold together at a combined price of $1.62, and each pre-funded warrant and accompanying common stock warrants were sold together at a combined price of $1.619, for gross proceeds of approximately $14.8 million. Each pre-funded warrant had an exercise price of $0.001 per share, became exercisable immediately upon issuance and continued to be exercisable until exercised in full. The accompanying common stock warrants have an exercise price of $1.37 per share and became exercisable immediately upon issuance. Of the accompanying common stock warrants, warrants to purchase an aggregate of 7,299,270 shares had an expiration date of April 5, 2025, warrants to purchase an aggregate of 1,851,852 shares had an expiration date of April 18, 2025, warrants to purchase an aggregate of 7,299,270 shares had an expiration date of October 5, 2028, and warrants to purchase an aggregate of 1,851,852 shares had an expiration date of October 18, 2028. As of October 31, 2024, all of the pre-funded warrants have been exercised, all of the accompanying common stock warrants expiring on April 5, 2025 have been exercised, and accompanying common stock warrants to purchase 1,299,270 shares expiring on October 5, 2028 have been exercised. Warrants to purchase 1,851,852 shares of common stock that are to expire on April 18, 2025, warrants to purchase

Previous wording

On April 11, 2022, we issued and sold in a private placement, or the April 2022 Private Placement, (i) an aggregate of 4,580,526 shares of our common stock, and (ii) pre-funded warrants to purchase up to an aggregate of 24,379,673 shares of our common stock. Each share of our common stock was sold at a price of $1.90, and each pre-funded warrant was sold at a price of $1.899 per warrant share, for gross proceeds of approximately $55.0 million. Each pre-funded warrant has an exercise price of $0.001 per share, became exercisable immediately upon issuance and will be exercisable until the pre-funded warrant is exercised in full. As of July 31, 2024 pre-funded warrants to purchase 15,282,760 shares of common stock that we issued and sold in the April 2022 Private Placement remained outstanding.

Current wording

On April 11, 2022, we issued and sold in a private placement, or the April 2022 Private Placement, (i) an aggregate of 4,580,526 shares of our common stock, and (ii) pre-funded warrants to purchase up to an aggregate of 24,379,673 shares of our common stock. Each share of our common stock was sold at a price of $1.90, and each pre-funded warrant was sold at a price of $1.899 per warrant share, for gross proceeds of approximately $55.0 million. Each pre-funded warrant has an exercise price of $0.001 per share, became exercisable immediately upon issuance and will be exercisable until the pre-funded warrant is exercised in full. As of October 31, 2024 pre-funded warrants to purchase 14,145,522 shares of common stock that we issued and sold in the April 2022 Private Placement remained outstanding.

Previous wording

On May 9, 2023, we paid the remaining amount due under the loan and security agreement, or the SVB Loan Agreement, that we originally entered into with Silicon Valley Bank, or SVB, in August 2020, resulting in the full extinguishment of the term loan thereunder, or the SVB Term Loan. The total payoff amount was $6.5 million, consisting of the remaining principal amount due of $5.2 million, the final payment fee of $1.2 million, and $0.1 million of accrued interest and prepayment premium. In August 2020, we entered into the SVB Loan Agreement with SVB, pursuant to which SVB provided the SVB Term Loan to us in the original principal amount of $14.0 million. On the first business day of each month commencing on March 1, 2022, we were required to repay the SVB Term Loan in 24 consecutive installments of principal plus monthly payments of accrued interest. All outstanding principal and accrued and unpaid interest under the SVB Term Loan and all other outstanding obligations with respect to the SVB Term Loan were due and payable in full on February 1, 2024. The SVB Loan Agreement permitted voluntary prepayment of all, but not less than all, of the SVB Term Loan, subject to a prepayment premium. For further discussion of the SVB Term Loan, see “—Liquidity and Capital Resources.”

Current wording

On May 9, 2023, we paid the remaining amount due under the loan and security agreement, or the SVB Loan Agreement, that we originally entered into with Silicon Valley Bank, or SVB, in August 2020, resulting in the full extinguishment of the term loan thereunder, or the SVB Term Loan. The total payoff amount was $6.5 million, consisting of the remaining principal amount due of $5.2 million, the final payment fee of $1.2 million, and $0.1 million of accrued interest and prepayment premium. For further discussion of the SVB Term Loan, see “—Liquidity and Capital Resources.”

Previous wording

As of June 30, 2024, we had cash, cash equivalents and marketable securities of $69.5 million. We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of issuance of the Condensed Consolidated Financial Statements included in this Quarterly Report on Form 10-Q.

Current wording

As of September 30, 2024, we had cash, cash equivalents and marketable securities of $65.5 million. We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements for at least 12 months from the date of issuance of the Condensed Consolidated Financial Statements included in this Quarterly Report on Form 10-Q.

Previous wording

We expect our research and development expenses to increase over the next few years as we pursue our development program, pursue regulatory approval of Haduvio in the U.S., Europe and other jurisdictions outside the U.S. and prepare for a possible commercial launch of Haduvio. Predicting the timing or the cost to conduct our Haduvio development program and prepare for a possible commercial launch of Haduvio is difficult and delays may occur because of many factors including factors outside of our control. For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on our development program. Furthermore, we are unable to predict when or if Haduvio will receive regulatory approval in the U.S. or elsewhere with any certainty.

Current wording

We expect our research and development expenses to increase as we pursue our development program, pursue regulatory approval of Haduvio in the U.S., Europe and other jurisdictions outside the U.S. and prepare for a possible commercial launch of Haduvio. Predicting the timing or the cost to conduct our Haduvio development program and prepare for a possible commercial launch of Haduvio is difficult and delays may occur because of many factors including factors outside of our control. For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on our development program. Furthermore, we are unable to predict when or if Haduvio will receive regulatory approval in the U.S. or elsewhere with any certainty.

Previous wording

Other income, net consists of income consists of foreign currency transaction gains and losses as well as employee retention tax credit under the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act.

Current wording

Other income, net consists of foreign currency transaction gains and losses as well as employee retention tax credit under the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act as well as an immaterial effect from the early extinguishment of debt in connection with us paying the remaining amounts due under the SVB Loan Agreement..

Previous wording

The SVB Term Loan required interest-only payments until March 2022. Commencing on March 1, 2022, we were required to repay the SVB Term Loan in 24 consecutive installments of principal plus monthly payments of accrued interest. On May 9, 2023, we paid the remaining amount due under the SVB Loan Agreement, resulting in the full extinguishment of the SVB Term Loan. The total payoff amount was $6.5 million, consisting of the remaining principal amount due of $5.2 million, the final payment fee of $1.2 million, and $0.1 million of accrued interest and prepayment premium.

Current wording

On May 9, 2023, we paid the remaining amount due under the SVB Loan Agreement, resulting in the full extinguishment of the SVB Term Loan. The total payoff amount was $6.5 million, consisting of the remaining principal amount due of $5.2 million, the final payment fee of $1.2 million, and $0.1 million of accrued interest and prepayment premium.

Previous wording

Research and development expenses for the three months ended June 30, 2024 increased to $10.0 million from $5.8 million for the corresponding period in 2023, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial, our HAP study and our recently initiated Phase 1b TIDAL study, as well as increases in personnel and related expenses and stock-based compensation expense. These increases were partially offset by decreased clinical development expenses for our Phase 2b/3 PRISM trial.

Current wording

Research and development expenses for the three months ended September 30, 2024 increased to $11.2 million from $6.3 million for the corresponding period in 2023, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial, and our HAP study as well as an increase in personnel related expenses.

Previous wording

Other income, net for the three months ended June 30, 2024 was $0.9 million compared to other income, net of $1.2 million for the corresponding period in 2023. The change was primarily due to a decrease in interest income due to lower cash equivalent and marketable securities balances.

Current wording

Other income, net for the three months ended September 30, 2024 was $0.8 million compared to other income, net of $1.3 million for the corresponding period in 2023. The change was primarily due to a decrease in interest income due to lower cash equivalent and marketable securities balances.

Previous wording

Comparison of the Six Months Ended June 30, 2024 and 2023

Current wording

Comparison of the Nine Months Ended September 30, 2024 and 2023

Previous wording

Research and development expenses for the six months ended June 30, 2024 increased to $18.8 million from $10.8 million for the corresponding period in 2023, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial, our HAP study and our recently initiated Phase 1b TIDAL study. These increases were partially offset by decreased clinical development expenses for our Phase 2b/3 PRISM trial.

Current wording

Research and development expenses for the nine months ended September 30, 2024 increased to $30.0 million from $17.2 million for the corresponding period in 2023, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial, our HAP study, and our Phase 1b TIDAL study. These increases were partially offset by decreased clinical development expenses for our Phase 2b/3 PRISM trial.

Previous wording

General and administrative expenses for the three months ended June 30, 2024 increased to $3.3 million from $2.5 million for the corresponding period in 2023, primarily due to increases in personnel and related expenses, stock-based compensation expense, market research costs as well as information technology services.

Current wording

General and administrative expenses for the nine months ended September 30, 2024 increased to $9.2 million from $7.8 million for the corresponding period in 2023, primarily due to increases in personnel related expenses, stock-based compensation expense, information technology services and market research costs.

Previous wording

Other income, net for the six months ended June 30, 2024 was $1.9 million compared to other income, net of $2.4 million for the corresponding period in 2023. The change was primarily due to a decrease in interest income of $0.5 million due to lower cash equivalent and marketable securities balances.

Current wording

Other income, net for nine months ended September 30, 2024 was $2.7 million compared to other income, net of $3.7 million for the corresponding period in 2023. The change was primarily due to a decrease in interest income of $0.9 million due to lower cash equivalent and marketable securities balances.

Previous wording

In June 2023, we filed with the SEC the Shelf Registration Statement, which allows us to offer and sell up to $200.0 million of common stock, preferred stock, debt securities, units and/or warrants from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale. The Shelf Registration Statement was filed to replace our prior universal shelf registration statement on Form S-3 and was declared effective on August 15, 2023. Further, in June 2023, we entered into the 2023 ATM Sales Agreement with Leerink Partners, under which we may issue and sell shares of common stock, from time to time by any method that is deemed an “at-the-market” offering as defined in Rule 415(a)(4) under the Securities Act. We are not obligated to make any sales of our common stock under the 2023 ATM Sales Agreement. We filed a prospectus under the Shelf Registration Statement for the offer and sale of shares of our common stock having an aggregate offering price of up to $75.0 million pursuant to the 2023 ATM Sales Agreement. In accordance with the terms of the 2023 ATM Sales Agreement, the ATM Sales Agreement terminated upon effectiveness of the Shelf Registration Statement, at which point we were no longer able to issue and sell shares of our common stock under the ATM Sales Agreement. As of June 30, 2024, we had issued and sold 1,474,926 shares of common stock for gross proceeds of $5.0 million, before deducting estimated commissions and allocated fees of $0.2 million under the 2023 ATM Sales Agreement.

Current wording

In June 2023, we filed with the SEC the Shelf Registration Statement, which allows us to offer and sell up to $200.0 million of common stock, preferred stock, debt securities, units and/or warrants from time to time pursuant to one or more offerings at prices and terms to be determined at the time of sale. The Shelf Registration Statement was filed to replace our prior universal shelf registration statement on Form S-3 and was declared effective on August 15, 2023. Further, in June 2023, we entered into the 2023 ATM Sales Agreement with Leerink Partners, under which we may issue and sell shares of common stock, from time to time by any method that is deemed an “at-the-market” offering as defined in Rule 415(a)(4) under the Securities Act. We are not obligated to make any sales of our common stock under the 2023 ATM Sales Agreement. We filed a prospectus under the Shelf Registration Statement for the offer and sale of shares of our common stock having an aggregate offering price of up to $75.0 million pursuant to the 2023 ATM Sales Agreement. In accordance with the terms of the 2023 ATM Sales Agreement, the ATM Sales Agreement terminated upon effectiveness of the Shelf Registration Statement, at which point we were no longer able to issue and sell shares of our common stock under the ATM Sales Agreement. As of September 30, 2024, we had issued and sold 3,086,729 shares of common stock for gross proceeds of $10.0 million, before deducting estimated commissions and allocated fees of $0.3 million under the 2023 ATM Sales Agreement. Subsequent to September 30, 2024, and through October 31, 2024, we issued and sold 1,411,336 shares of common stock under the 2023 ATM Sales Agreement for gross proceeds of $4.6 million, before deducting estimated commissions and allocated fees of $0.1 million.

Previous wording

During the six months ended June 30, 2024, operating activities used $19.2 million of net cash, resulting from our net loss of $23.3 million partially offset by net changes in our operating assets and liabilities of $2.7 million and net non-cash charges of $1.4 million. Changes in our operating assets and liabilities consisted of a $1.9 million decrease in prepaid expenses and other current assets and a $1.1 million increase in accrued expenses and other liabilities partially offset by a $0.3 million decrease in accounts payable. The decrease in prepaid expenses and other current assets was primarily due to a decrease in prepayments related to our clinical trial work performed by our CROs. The increase in accrued expenses and other liabilities was primarily due to an increase in accruals for clinical development and clinical trial work performed by our CROs. The decrease in accounts payable was primarily due to the timing of vendor invoices. The non-cash charges consisted primarily of stock-based compensation expense of $1.9 million, $0.2 million change in value of our operating lease right-of-use assets and liabilities and $0.1 million of depreciation and amortization, partially offset by $0.7 million of accretion of our available-for-sale marketable securities.

Current wording

During the nine months ended September 30, 2024, operating activities used $28.7 million of net cash, resulting from our net loss of $36.5 million partially offset by net changes in our operating assets and liabilities of $5.8 million and net non-cash charges of $2.0 million. Changes in our operating assets and liabilities consisted of a $3.3 million increase in accrued expenses and other liabilities and a $2.7 million decrease in prepaid expenses and other current assets partially offset by a $0.2 million decrease in accounts payable. The increase in accrued expenses and other liabilities was primarily due to an increase in accruals for clinical development and clinical trial work performed by our CROs. The decrease in prepaid expenses and other current assets was primarily due to a decrease in prepayments related to our clinical trial work performed by our CROs. The decrease in accounts payable was primarily due to the timing of vendor invoices. The non-cash charges consisted primarily of stock-based compensation expense of $2.7 million, $0.3 million change in value of our operating lease right-of-use assets and liabilities and $0.1 million of depreciation and amortization, partially offset by $1.1 million of accretion of our available-for-sale marketable securities.

Previous wording

During the six months ended June 30, 2023, operating activities used $18.1 million of net cash, principally resulting from our net loss of $13.5 million and net changes in our operating assets and liabilities of $4.8 million. Changes in our operating assets and liabilities consisted of a $2.5 million increase in prepaid expenses and other current assets, a $1.5 million decrease in accounts payable and a $0.8 million decrease in accrued expenses and other liabilities. The increase in prepaid expenses and other current assets was primarily due to an increase in prepayments related to our clinical trial work performed by our CROs as well as an increase in prepayments of our corporate insurance policies. The decrease in accounts payable was primarily due to the timing of vendor invoices. The decrease in accrued expenses and other liabilities was primarily due to a decrease in accrued compensation and benefits and interest payable partially offset by an increase in accruals for research, development and clinical trial work performed by our CROs and consultants. Net cash used in operating activities for the six months ended June 30, 2023 also included non-cash charges that consisted primarily of stock-based compensation expense of $1.2 million and $0.2 million of accretion/accrual of term loan discounts and debt issuance costs, which were partially offset by $1.3 million of accretion of our available-for-sale marketable securities.

Current wording

During the nine months ended September 30, 2023, operating activities used $25.4 million of net cash, principally resulting from our net loss of $21.2 million and net changes in our operating assets and liabilities of $4.6 million. Changes in our operating assets and liabilities consisted of a $2.9 million increase in prepaid expenses and other current assets, a $1.7 million decrease in accounts payable and a slight increase in accrued expenses and other liabilities. The increase in prepaid expenses and other current assets was primarily due to an increase in prepayments related to our clinical trial work performed by our CROs as well as an increase in prepayments of our corporate insurance policies. The decrease in accounts payable was primarily due to the timing of vendor invoices. The increase in accrued expenses and other liabilities was primarily due to a decrease in accrued compensation and benefits and interest payable partially offset by an increase in accruals for research, development and clinical trial work performed by our CROs and consultants. Net cash used in operating activities for the nine months ended September 30, 2023, also included non-cash charges that consisted primarily of stock-based compensation expense of $1.7 million, a $0.3 million change in value of our operating lease right-of-use assets and $0.2 million of accretion/accrual of term loan discounts and debt issuance costs, which were partially offset by $1.8 million of accretion of our available-for-sale marketable securities.

Previous wording

During the six months ended June 30, 2024, net cash used in investing activities was $5.3 million, primarily related to $40.2 million of purchases of available-for-sale marketable securities, partially offset by $34.9 million of proceeds from maturities of available-for-sale marketable securities.

Current wording

During the nine months ended September 30, 2024, net cash provided by investing activities was $2.3 million, primarily related to $55.6 million of proceeds from maturities of available-for-sale marketable securities partially offset by $53.3 million of purchases of available-for-sale marketable securities.

Previous wording

During the six months ended June 30, 2023, net cash provided by investing activities was $28.6 million, consisting primarily of $37.7 million of proceeds from maturities of available-for-sale marketable securities partially offset by $9.0 million of purchases of available-for-sale marketable securities.

Current wording

During the nine months ended September 30, 2023, net cash provided by investing activities was $46.6 million, consisting primarily of $55.7 million of proceeds from maturities of available-for-sale marketable securities partially offset by $9.0 million of purchases of available-for-sale marketable securities and $0.1 million of purchases property, equipment and leasehold improvements.

Previous wording

During the six months ended June 30, 2024, net cash provided by financing activities was $5.0 million, primarily consisting of gross cash proceeds of $5.0 million, net of commissions from sales of our common stock under the 2023 ATM Sales Agreement, and $0.2 million of cash proceeds from the exercise of stock options, partially offset by $0.1 million of payments on our finance lease.

Current wording

During the nine months ended September 30, 2024, net cash provided by financing activities was $10.0 million, primarily consisting of cash proceeds of $9.7 million, net of commissions, from sales of our common stock under the 2023 ATM Sales Agreement, and $0.4 million of cash proceeds from the exercise of stock options, partially offset by $0.1 million of payments on our finance lease.

Previous wording

During the six months ended June 30, 2023, net cash used in financing activities was $9.4 million, consisting of repayments of $9.4 million on the SVB Term Loan including payment of the final payment fee and prepayment premium, both associated with the payoff of the SVB Term Loan.

Current wording

During the nine months ended September 30, 2023, net cash used in financing activities was $7.9 million, consisting primarily of repayments of $9.4 million on the SVB Term Loan including payment of the final payment fee and prepayment premium, both associated with the payoff of the SVB Term Loan, and payments of offering costs of $0.2 million. These cash outflows were partially offset by cash proceeds of $1.7 million, net of commissions, from sales of our common stock under the ATM Sales Agreement and $0.1 million of cash proceeds from the exercise of stock options and sales under our 2019 Employee Stock Purchase Plan.

Previous wording

the scope, progress, timing, costs and results of clinical trials of Haduvio, including our Phase 2b CORAL clinical trial of Haduvio for the treatment of chronic cough in IPF, our Phase 2a RIVER clinical trial in RCC, our HAP study, and our Phase 1b TIDAL study to evaluate the effect of Haduvio on respiratory physiology in patients with IPF of varying disease severity, as well as trials for any future product candidates;

Current wording

the scope, progress, timing, costs and results of clinical trials of Haduvio, including our Phase 2b CORAL clinical trial of Haduvio for the treatment of chronic cough in IPF, our Phase 2a RIVER clinical trial in RCC, our HAP study, and our

Previous wording

the costs associated with the manufacture of necessary quantities of Haduvio or any future product candidate for clinical development in connection with regulatory submissions;

Current wording

the costs to manufacture necessary quantities of Haduvio or any future product candidate for clinical development in connection with regulatory submissions;

Previous wording

We believe that our existing cash, cash equivalents and marketable securities, will enable us to fund our operating expenses and capital expenditure requirements into 2026. Our current plans do not take into account the cost of any additional clinical trials for the treatment of prurigo nodularis.

Current wording

We believe that our existing cash, cash equivalents and marketable securities, will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2026. Our current plans do not take into account the cost of any additional clinical trials of Haduvio.

Previous wording

While our significant accounting policies are described in the Notes to our financial statements, we believe that the critical accounting policy related to research and development expenses that is described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Use of Estimates” in our Annual Report on Form 10-K for the year ended December 31, 2023, is the most important to understanding and evaluating our reported financial results. During the six months ended June 30, 2024, there were no material changes to our critical accounting policies.

Current wording

While our significant accounting policies are described in the Notes to our financial statements, we believe that the critical accounting policy related to research and development expenses that is described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Use of Estimates” in our Annual Report on Form 10-K for the year ended December 31, 2023, is the most important to understanding and evaluating our reported financial results. During the nine months ended September 30, 2024, there were no material changes to our critical accounting policies.