On May 4, 2023 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health" or the "Company" or "we" or "our") reported its first-quarter 2023 financial results (Press release, Bausch Health, MAY 4, 2023, View Source [SID1234631000]).

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"We are encouraged with the top-line improvement in the first quarter, with four out of five segments delivering revenue growth on both a reported revenue and organic basis1 and are pleased that demand for key products has remained resilient in the current macro environment," said Thomas J. Appio, Chief Executive Officer, Bausch Health. "We are progressing our mid- and late-stage pipeline, and we look forward to bringing new products to the patients who can benefit from them," concluded Appio.

Bausch Health (excl. B+L) Pipeline Update
•Amiselimod: Phase 2 trial is progressing and expected to be completed in the second half of 2023.
•RED-C: Investments related to Reduction of Early Decompensation in Cirrhosis (RED-C) program have accelerated. Two global Phase 3 studies are currently underway and enrollment is on-track. The Company held scientific advisory meetings with the Medicines Evaluation Board (MEB) in the Netherlands and with Health Canada, and plans to engage with relevant authorities in Japan and China later this year.
•IDP-126: The FDA accepted the Company’s new drug application and received an October 20, 2023, PDUFA date. If approved by the FDA, IDP-126 would be a first-in-class treatment with a triple combination of benzoyl peroxide, clindamycin phosphate and adapalene. A submission in Canada is planned for the second quarter of this year.
•Solta Medical: We are planning a regulatory submission for Clear and Brilliant Touch in Europe and Canada in 2024 and for Asia Pacific markets in 2025. FDA submission is expected for Next Generation Fraxel in Q4 2023.

First Quarter 2023 Revenue Performance
Total reported revenues were $1.94 billion for the first quarter of 2023, compared with $1.92 billion in the first quarter of 2022, an increase of $26 million, or 1%. Excluding the unfavorable impact of foreign exchange of $40 million and the impact of acquisitions, divestitures, and discontinuations of $7 million, revenue increased by 4% organically1 compared with the first quarter of 2022.

1 This is a non-GAAP measure or a non-GAAP ratio. For further information on non-GAAP measures and non-GAAP ratios, please refer to the "Non-GAAP Information" section of this news release. Please also refer to tables at the end of this news release for a reconciliation of this and other non-GAAP measures to the most directly comparable GAAP measure.

Reported revenues by segment were as follows:

Three Months Ended March 31, Reported Change
Change at Constant Currency1
(Non-GAAP)
Change in Organic Revenue1
(Non-GAAP)
(in millions) 2023 2022 Amount Pct.
Total Bausch Health Revenues $1,944 $1,918 $26 1 % 3 % 4 %
Bausch Health (excl. B+L) $1,013 $1,029 ($16) (2 %) (1 %) — %
Salix segment $496 $464 $32 7 % 7 % 7 %
International segment $247 $244 $3 1 % 4 % 5 %
Solta Medical segment $73 $72 $1 1 % 6 % 6 %
Diversified segment $197 $249 ($52) (21 %) (21 %) (21 %)
Bausch + Lomb segment $931 $889 $42 5 % 8 % 8 %

Salix Segment
Salix segment reported and organic1 revenues were $496 million for the first quarter of 2023, compared with $464 million for the first quarter of 2022, an increase of $32 million, or 7%. Sales growth was driven by Xifaxan, Relistor, and Trulance.

International Segment
International segment reported revenues were $247 million for the first quarter of 2023, compared with $244 million for the first quarter of 2022, an increase of $3 million, or 1%. Excluding the unfavorable impact of foreign exchange of $6 million and the impact of divestitures and discontinuations of $3 million, segment revenues increased organically1 by 5% compared with the first quarter of 2022, led by organic growth in Canada and Europe.

Solta Medical Segment
Solta Medical segment reported revenues were $73 million for the first quarter of 2023, compared with $72 million in the first quarter of 2022, an increase of $1 million, or 1%. Excluding the unfavorable impact of foreign exchange of $3 million, segment revenues increased organically1 by 6% compared with the first quarter of 2022.

Diversified Segment
Diversified segment reported and organic1 revenues were $197 million for the first quarter of 2023, compared with $249 million for the first quarter of 2022, a decrease of $52 million, or 21%, primarily attributable to decreases in sales across Neurology, Generics and Dermatology, partially offset by an increase in sales in Dentistry.

Bausch + Lomb Segment
Bausch + Lomb segment reported revenues were $931 million for the first quarter of 2023, compared with $889 million for the first quarter of 2022, an increase of $42 million, or 5%. Excluding the unfavorable impact of foreign exchange of $31 million, the impact of acquisitions of $2 million and the impact of divestitures and discontinuations of $2 million, the Bausch + Lomb segment revenue increased organically1 by 8%, compared with the first quarter of 2022, driven by increases across all business units.

Consolidated Operating Income
Consolidated operating income was $175 million for the first quarter of 2023, compared with operating income of $285 million for the first quarter of 2022, a decrease of $110 million. The change is primarily due to higher SG&A expenses, reflecting investments in selling and marketing, and R&D, as well as non-cash charges associated with adjustments to the fair value of acquisition related contingent consideration, offset by lower amortization of intangibles.

Net Loss Attributable to Bausch Health
Net loss attributable to Bausch Health for the first quarter of 2023 was $201 million, compared with a net loss of $69 million for the first quarter of 2022, an unfavorable change of $132 million. This was primarily due to the increase in loss before income taxes of $54 million, and an unfavorable change in income taxes of $89 million.

Adjusted net income attributable to Bausch Health (non-GAAP)1 for the first quarter of 2023 was $191 million, compared with $263 million for the first quarter of 2022, a decrease of $72 million primarily due to higher operating expenses and foreign exchange headwinds.

Loss Per Share Attributable to Bausch Health
GAAP Loss Per Share attributable to Bausch Health for the first quarter of 2023 was $(0.55), compared with $(0.19) for the first quarter of 2022.

Adjusted EBITDA Attributable to Bausch Health (non-GAAP)1
Adjusted EBITDA attributable to Bausch Health (non-GAAP)1 was $588 million for the first quarter of 2023, as compared to $732 million for the first quarter of 2022, a decrease of $144 million.

Cash Provided by (Used in) Operating Activities
The company generated $154 million of cash in the first quarter of 2023 compared with using $63 million of cash in the first quarter of 2022. The increase in cash flow from operations is primarily attributable to: (i) a decrease in payments of accrued legal settlements related to the Glumetza Antitrust Litigation in first quarter 2022 and (ii) a portion of cash interest payments being classified as Cash Flows from Financing activities as a result of the accounting treatment required for the Company’s New Secured Notes issued in September 2022, partially offset by (iii) changes in business performance.

Balance Sheet Highlights as of March 31, 2023:
•Cash and cash equivalents were $531 million.
•Bausch Health (excl. B+L) had availability under its 2027 revolving credit facility of approximately $557 million and Bausch + Lomb had availability of approximately $376 million under its revolving credit facility.

2023 Financial Outlook
The Company confirmed its full year guidance for Bausch Health (excl. B+L) and is providing full year consolidated guidance as follows:
•Full year revenue range of $8.35 – $8.55 billion
•Full year Adjusted EBITDA (non-GAAP)1 range of $3.00 – $3.15 billion

Other than with respect to GAAP revenues, the Company only provides guidance on a non-GAAP basis. The Company does not provide a reconciliation of forward-looking Adjusted EBITDA (non-GAAP)1 to GAAP net income (loss), due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation. Because deductions (such as restructuring, gain or loss on extinguishment of debt and litigation and other matters) used to calculate projected net income (loss) vary dramatically based on actual events, the Company is not able to forecast on a GAAP basis with reasonable certainty all deductions needed in order to provide a GAAP calculation of projected net income (loss) at this time. The amount of these deductions may be material and, therefore, could result in projected GAAP net income (loss) being materially less than projected Adjusted EBITDA (non-GAAP)1. These statements represent forward-looking information and may represent a financial outlook, and actual results may vary. Please see the risks and assumptions referred to in the Forward-looking Statements section of this news release. The guidance in this news release is only effective as of the date it is given, and will not be updated or affirmed unless and until the Company publicly announces updated or affirmed guidance.

Conference Call Details
Date:
Thursday, May 4, 2023
Time: 8:00 a.m. ET
Webcast: View Source

A replay of the conference call will be available on the investor relations website.

On May 4, 2023 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases, reported first quarter 2023 financial results and provided a corporate update (Press release, Arbutus Biopharma, MAY 4, 2023, View Source [SID1234630999]).

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"In the first quarter of 2023, we made meaningful progress advancing our pipeline of HBV and coronavirus assets to address large global market opportunities," said William Collier, Arbutus’ President and Chief Executive Officer. "We reported data from our lead HBV-focused RNAi therapeutic, AB-729, showing low levels of HBsAg and HBV DNA in most patients persisting for at least a year and a half after their last dose of AB-729. In addition, we dosed the first healthy subject in our Phase 1 clinical trial with AB-161, our oral RNA destabilizer, for which we expect data in the second half of this year. We continue to advance our coronavirus programs and expect to initiate a Phase 1 clinical trial with our Mpro inhibitor candidate, AB-343, as well as IND-enabling studies for an nsp12 inhibitor candidate in the second half of this year."

Pipeline Updates and Key Milestones

AB-729 (RNAi Therapeutic)

At the Global Hepatitis Summit in April, we reported in an oral presentation additional off-treatment data from the patients in our Phase 1b clinical trial (AB-729-001) who have discontinued both AB-729 and nucleos(t)ide analogue (NA) therapy. These seven remaining patients continue to maintain low HBV DNA levels off all therapy, and HBsAg levels remain below baseline (-0.8 to -1.6 log10) up to one and a half years after the last dose of AB-729.
We are continuing to evaluate the safety and tolerability of AB-729 in combination with ongoing NA therapy and short courses of PEG-IFNα-2a (IFN) in 43 patients with chronic hepatitis B virus (cHBV) infection in a Phase 2a clinical trial (AB-729-201). Preliminary data from the lead-in phase of the trial further validated AB-729’s capacity to reduce HBsAg. We expect to announce preliminary data from patients receiving the combination of AB-729, NA therapy and IFN in the second quarter of 2023.
We are continuing to evaluate AB-729, NA therapy and Vaccitech’s HBV antigen-specific immunotherapeutic, VTP-300, in a Phase 2a clinical trial (AB-729-202). Once enrollment is complete in the initial portion of this trial, we will begin enrolling 20 patients in an additional arm of the trial. These patients will receive AB-729 (60mg every 8 weeks) plus NA therapy for 24 weeks, followed by VTP-300 plus one to two low doses of nivolumab (Opdivo). We expect preliminary data from patients who receive AB-729, NA therapy and VTP-300 in the second half of 2023, and we expect to dose the first patient in the additional arm receiving AB-729, NA therapy, VTP-300 and nivolumab in the second quarter of 2023.
AB-161 (Oral RNA destabilizer)

In March, we dosed the first healthy subject in our Phase 1 clinical trial with AB-161. The single-ascending dose data is expected in the second half of 2023. AB-161 is our next-generation oral HBV-specific RNA destabilizer, which is being developed as part of a potential all-oral treatment regimen to functionally cure HBV.
At the Global Hepatitis Summit in April, we presented preclinical data showing that AB-161 provides robust anti-HBV activity including suppression of HBV RNA and HBsAg production in vitro and in vivo. The differentiated anti-HBV mode of action of AB-161 compared to other classes of HBV inhibitors, suggest that AB-161 may be an important component in combination to provide a functional cure for cHBV.
AB-101 (Oral PD-L1 Inhibitor)

In April, we received verbal communication from the U.S. Food and Drug Administration (FDA) that the AB-101 Investigational New Drug (IND) application has been placed on clinical hold. For purposes of clarity, the Phase 1 clinical trial had not been initiated and we had not dosed any patients with AB-101. The FDA indicated they will provide an official clinical hold letter to Arbutus within 30 days of the verbal communication. Based on this communication, we no longer intend to report initial data from the single-ascending dose portion of a Phase 1 clinical trial in the second half of 2023. We are developing AB-101, our oral PD-L1 inhibitor, to reawaken and boost the immune system of patients with cHBV. Preclinical data generated thus far indicates that AB-101 is highly potent and mediates activation and reinvigoration of HBV-specific T-cells from cHBV patients.
COVID-19 and Pan-Coronavirus Programs

At the 36th International Conference on Antiviral Research in March, we presented pre-clinical data for AB-343, our lead coronavirus drug candidate that inhibits the main protease (Mpro). The antiviral potency, selectivity and favorable pharmacokinetic data support the further development of AB-343 as a potential ritonavir-free oral treatment for COVID-19 and other human coronaviruses. We are currently conducting IND-enabling studies with AB-343, and on completion, we expect to initiate a Phase 1 clinical trial in the second half of 2023.
We are continuing to direct our research efforts to identifying an nsp12 viral polymerase clinical candidate. Such a candidate could potentially be combined with AB-343 to achieve better patient treatment outcomes and for use in prophylactic settings. We expect to nominate an nsp12 clinical candidate and initiate IND-enabling studies in the second half of 2023.
Financial Results

Cash, Cash Equivalents and Investments

As of March 31, 2023, we had cash, cash equivalents and investments in marketable securities of $178.5 million compared to $184.3 million as of December 31, 2022. During the three months ended March 31, 2023, we used $27.3 million in operating activities, which was partially offset by $19.9 million of net proceeds from the issuance of common shares under our "at-the-market" offering program. Based on AB-101’s IND being placed on clinical hold by the FDA and a resulting shift in the timing of our AB-101 Phase 1 clinical trial, we are reducing our 2023 cash burn guidance from between $95 to $100 million to between $90 to $95 million. We believe our cash runway will be sufficient to fund our operations into the first quarter of 2025.

Revenue

Total revenue was $6.7 million for the three months ended March 31, 2023 compared to $12.6 million for the same period in 2022. The decrease of $5.9 million was due primarily to less revenue recognition from our license agreement with Qilu compared to last year based on employee labor hours expended by us to perform our manufacturing obligations under the license agreement.

Operating Expenses

Research and development expenses were $18.3 million for the three months ended March 31, 2023 compared to $18.5 million for the same period in 2022. The decrease of $0.2 million was due primarily to a decrease in expenses for our AB-836 Phase 1a/1b clinical trial, which was discontinued in the fourth quarter of 2022, partially offset by an increase in expenses for our coronavirus program and other early-stage development programs.

Net Loss

For the three months ended March 31, 2023, our net loss was $16.3 million, or a loss of $0.10 per basic and diluted common share, as compared to a net loss of $15.8 million, or a loss of $0.11 per basic and diluted common share, for the three months ended March 31, 2022. Net loss for the three months ended March 31, 2022 included $4.4 million of income tax expense for withholding taxes paid to the Chinese taxing authority by Qilu on our behalf in connection with the upfront license fee Qilu paid us.

Outstanding Shares

As of March 31, 2023, we had approximately 165.1 million common shares issued and outstanding, as well as approximately 19.7 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 23% of our outstanding common shares as of March 31, 2023.

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(in thousands, except share and per share data)

Three Months Ended March 31,
2023 2022
Revenue
Collaborations and licenses $ 5,509 $ 11,218
Non-cash royalty revenue 1,178 1,363
Total revenue 6,687 12,581
Operating expenses
Research and development 18,275 18,462
General and administrative 5,552 4,892
Change in fair value of contingent consideration 273 201
Total operating expenses 24,100 23,555
Loss from operations (17,413 ) (10,974 )
Other income (loss)
Interest income 1,268 159
Interest expense (198 ) (506 )
Foreign exchange gain 4 —
Total other income (loss) 1,074 (347 )
Loss before income taxes (16,339 ) (11,321 )
Income tax expense — (4,444 )
Net loss $ (16,339 ) $ (15,765 )
Net loss per common share
Basic and diluted $ (0.10 ) $ (0.11 )
Weighted average number of common shares
Basic and diluted 161,643,404 148,428,326

UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands)

March 31, 2023 December 31, 2022
Cash, cash equivalents and marketable securities, current $ 146,728 $ 146,913
Accounts receivable and other current assets 6,126 4,226
Total current assets 152,854 151,139
Property and equipment, net of accumulated depreciation 4,853 5,070
Investments in marketable securities, non-current 31,790 37,363
Right of use asset 1,665 1,744
Other non-current assets 62 103
Total assets $ 191,224 $ 195,419
Accounts payable and accrued liabilities $ 9,653 $ 16,029
Deferred license revenue, current 15,055 16,456
Lease liability, current 446 372
Total current liabilities 25,154 32,857
Liability related to sale of future royalties 9,384 10,365
Deferred license revenue, non-current 3,296 5,999
Contingent consideration 7,804 7,531
Lease liability, non-current 1,671 1,815
Total stockholders’ equity 143,915 136,852
Total liabilities and stockholders’ equity $ 191,224 $ 195,419

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)

Three Months Ended March 31,
2023 2022
Net loss $ (16,339 ) $ (15,765 )
Non-cash items 1,372 1,642
Change in deferred license revenue (4,104 ) 38,840
Other changes in working capital (8,230 ) (4,098 )
Net cash (used in) provided by operating activities (27,301 ) 20,619
Net cash provided by (used in) investing activities 16,678 (60,056 )
Issuance of common shares pursuant to Share Purchase Agreement — 10,973
Issuance of common shares pursuant to the Open Market Sale Agreement 19,862 268
Cash provided by other financing activities 555 244
Net cash provided by financing activities 20,417 11,485
Effect of foreign exchange rate changes on cash and cash equivalents 4 -
Increase (decrease) in cash and cash equivalents 9,798 (27,952 )
Cash and cash equivalents, beginning of period 30,776 109,282
Cash and cash equivalents, end of period 40,574 81,330
Investments in marketable securities 137,944 153,500
Cash, cash equivalents and marketable securities, end of period $ 178,518 $ 234,830

Conference Call and Webcast Today

Arbutus will hold a conference call and webcast today, Thursday, May 4, 2023, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus’ website at www.arbutusbio.com.

An archived webcast will be available on the Arbutus website after the event.

About AB-729

AB-729 is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. AB-729 targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. AB-729 is currently in multiple Phase 2a clinical trials.

About AB-101

AB-101 is our lead oral PD-L1 inhibitor candidate that we believe will allow for controlled checkpoint blockade and enable oral dosing, while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates activation and reinvigoration of HBV-specific T-cells from cHBV patients. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in HBV chronically infected patients. We are also exploring oncology applications for our internal PD-L1 portfolio.

About AB-161

AB-161 is our next generation oral small molecule RNA destabilizer, specifically designed to target the liver. Mechanistically, RNA destabilizers target the host proteins PAPD5/7, which are involved in regulating the stability of HBV RNA transcripts. In doing so, RNA destabilizers lead to the selective degradation of HBV RNAs, thus reducing HBsAg levels and inhibiting viral replication. To provide a proprietary all-oral treatment regimen for patients with cHBV, we believe inclusion of a small molecule RNA destabilizer is key.

About AB-343

AB-343 is our lead coronavirus drug candidate that inhibits the SARS-CoV-2 main protease (Mpro), a validated target for the treatment of COVID-19 and potential future coronavirus outbreaks. In our pre-clinical research conducted to date, AB-343 has shown pan-coronavirus antiviral activity, no reduction in potency against known SARS-CoV-2 variants, robust activity against SARS-CoV-2 Mpro resistant strains, and a favorable drug-drug interaction profile with no need for ritonavir boosting. We see an opportunity to pursue a potential combination therapeutic strategy focusing on Mpro and nsp12 viral polymerase targets to reduce hospitalizations, achieve better patient treatment outcomes and provide pre-exposure prophylactic therapy.

About HBV

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 290 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options. 

On May 4, 2023 Amphista Therapeutics, a leader in next generation targeted protein degradation (TPD) approaches, reported the delivery of the first discovery milestone under its collaboration and license agreement with Bristol Myers Squibb, triggering a payment for achieving the milestone (Press release, Amphista Therapeutics, MAY 4, 2023, View Source [SID1234630998]).

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Nicola Thompson, CEO of Amphista, said, "we are absolutely delighted with the progress and success of our collaboration with BMS. Our ability to deliver our first milestone within the first year of our collaboration exemplifies the strength of our Eclipsys TM platform and our ambition to be a world-leading, next generation protein degradation company."

The collaboration and license agreement with Bristol Myers Squibb was announced on May 4, 2022 and included a $30 million upfront payment, the potential for up to $1.25 billion in performance-based milestone payments and payment for a limited expansion of the collaboration, as well as royalties on global net sales of products. Amphista is responsible for the discovery and development of small molecule protein degraders using Eclipsys TM, its next-generation TPD platform. Bristol Myers Squibb is granted a global exclusive license to the resulting degraders and will be responsible for further development and commercialization activities.

Amphista’s next generation bifunctional molecules use a novel approach that makes use of a wider range of the body’s own innate protein degrading mechanisms than those used by most other TPD companies. This proprietary approach offers the potential to overcome many of the limitations seen with current TPD approaches, providing the opportunity to treat a wider range of diseases. Amphista is focused on biological targets with a high level of clinical or genetic validation.

On May 4, 2023 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to discovering and developing innovative therapies designed to treat immune-mediated diseases, reported recent corporate highlights and financial results for the quarter ended March 31, 2023 (Press release, Aldeyra Therapeutics, MAY 4, 2023, View Source [SID1234630997]).

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"Aldeyra continues to build a robust pipeline of novel drug candidates for the treatment of immune-mediated diseases," stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. "Multiple regulatory and clinical catalysts are planned for the coming quarters, including PDUFA dates for ADX-2191 and reproxalap, top-line results from our Phase 2 clinical trials in retinitis pigmentosa and chronic cough, and top-line results from our Phase 3 INVIGORATE-2 trial in allergic conjunctivitis."

Recent Corporate Highlights

Enrollment Completed in the Phase 2 Clinical Trial of ADX‑2191 in Retinitis Pigmentosa: The open-label, single-center Phase 2 clinical trial enrolled a total of eight retinitis pigmentosa patients with rhodopsin gene mutations, including the P23H gene mutation. Patients receive either monthly or twice-monthly intravitreal doses of ADX‑2191 for three months. The primary endpoint of the trial is safety. Secondary endpoints include change from baseline in visual acuity; retinal function, as assessed by foveal microperimetry, electroretinography, and dark adaptation; and retinal morphology, as assessed by optical coherence tomography. ADX-2191, an investigational drug candidate, is a novel intravitreal formulation of methotrexate, which in preclinical models of retinitis pigmentosa facilitates the clearance of misfolded rhodopsin, a critical visual cycle protein susceptible to genetic mutation.1 Top-line results from the Phase 2 clinical trial are expected in the second quarter of 2023.
Enrollment Completed in the Phase 2 Clinical Trial of ADX-629 in Chronic Cough: The multicenter, randomized, double-blind, placebo-controlled, two-period Phase 2 crossover trial enrolled 51 patients with refractory or unexplained chronic cough, which is often defined as a cough that persists for more than eight weeks. Patients were randomized to receive ADX-629 or placebo twice daily for two weeks, followed by a two-week washout period prior to crossing over to two weeks of treatment with ADX-629 or placebo, whichever was not received in the first period. The primary endpoint of the trial is safety. Secondary endpoints include awake cough frequency, 24-hour cough frequency, patient-reported cough severity, quality of life, and patient and clinician global impression of change. ADX-629, an investigational new drug candidate, is a novel, orally administered RASP (reactive aldehyde species) modulator for the potential treatment of systemic immune-mediated diseases. RASP were observed in a preliminary observational study to be elevated in the bronchioalveolar lavage fluid of patients with chronic cough,2 and may contribute to neurosensory dysfunction as well as inflammation. Top-line results from the Phase 2 clinical trial are expected in the second quarter of 2023.
First Patient Enrolled in the Phase 2 Clinical Trial of ADX-629 in Atopic Dermatitis: The multicenter, adaptive, two-part Phase 2 clinical trial will evaluate the safety and efficacy of ADX‑629 alone and in combination with standard of care in adults with mild, moderate, or severe atopic dermatitis. In Part 1, approximately 10 patients will receive open-label ADX‑629 twice daily for three months. Outcomes will include improvement in Investigator Global Assessment and Eczema Area and Severity Index scores. In patients with atopic dermatitis, the pro-inflammatory RASP malondialdehyde is elevated compared to levels observed in healthy controls.3 Top-line results from Part 1 are expected in the second half of 2023. Pending the results of Part 1, Part 2 will randomize patients to receive either ADX‑629 or placebo treatment twice daily for three months.
Enrollment Completed in the Phase 3 INVIGORATE-2 Clinical Trial of Reproxalap in Allergic Conjunctivitis: The randomized, double-masked, crossover, vehicle-controlled Phase 3 clinical trial enrolled 131 seasonal allergic conjunctivitis patients who were evaluated for 3.5 hours in an allergen chamber designed to simulate real-world pollen exposure. Consistent with pivotal trials of approved allergic conjunctivitis products, the primary endpoint of INVIGORATE-2 is patient-reported ocular itching. The protocol of INVIGORATE-2 is substantially identical to that of the Phase 3 INVIGORATE clinical trial and a Phase 2 clinical trial,4 both of which achieved the ocular itching endpoint (P<0.001). Reproxalap, an investigational new drug candidate, is a first-in-class small-molecule modulator of RASP, which are elevated in ocular and systemic inflammatory disease. Top-line results from the Phase 3 INVIGORATE-2 clinical trial are expected in second quarter of 2023.
Additional Planned Clinical and Regulatory Milestones

Results from Phase 2 Clinical Trials of ADX-629: Top-line results from Phase 2 clinical trials of ADX‑629 in idiopathic nephrotic syndrome (Part 1) and Sjögren-Larsson Syndrome are expected in the second half of 2023. Idiopathic nephrotic syndrome is a rare inflammatory kidney disease characterized by inflammation. Sjögren-Larsson Syndrome is an inborn error of metabolism characterized by mutations in an enzyme that metabolizes RASP.
Type C Meeting with the FDA for ADX-2191 in Proliferative Vitreoretinopathy: Aldeyra plans to conduct a Type C meeting with the U.S. Food and Drug Administration in the second half of 2023 to discuss the completion of clinical development of ADX‑2191 for the prevention of proliferative vitreoretinopathy, a rare sight-threatening disease that occurs following retinal detachment.
Initiation of Clinical Trials of Next-Generation RASP-Modulator Drug Candidates for Systemic Immune-Mediated Diseases and Geographic Atrophy: Pending completion of Investigational New Drug requirements, a Phase 1 clinical trial of orally administered ADX‑246 for the treatment of systemic immune-mediated diseases, and a Phase 1/2 clinical trial of intravitreally injected ADX‑248 for the treatment of geographic atrophy, a sight-threatening retinal disease, are expected to initiate in the second half of 2023 or early 2024.
First-Quarter 2023 Financial Results

Cash and cash equivalents as of March 31, 2023 were $165.0 million. Based on its current operating plan, Aldeyra believes that existing cash and cash equivalents will be sufficient to fund currently projected operating expenses into the second half of 2024, including the initial commercialization and launch plans for reproxalap and ADX-2191, if approved, and continued early and late-stage development of Aldeyra’s product candidates in ocular and systemic immune-mediated diseases.

Net loss for the three months ended March 31, 2023 was $15.6 million, or $0.27 per share, compared with a net loss of $16.8 million, or $0.29 per share, for the comparable period of 2022.

Research and development expenses for the three months ended March 31, 2023 were $11.2 million, compared with $12.2 million for the same period in 2022. The decrease of $1.0 million was primarily related to a decrease in external clinical development costs, offset by an increase in personnel costs, drug product manufacturing expenditures, external preclinical development costs, and consulting expenditures.

General and administrative expenses for the three months ended March 31, 2023 were $5.6 million, compared with $4.2 million for the same period in 2022. The increase of $1.4 million was primarily related to higher personnel costs and legal expenditures, offset by a decrease in consulting expenditures.

Total operating expenses for the three months ended March 31, 2023 were $16.8 million, compared with total operating expenses of $16.5 million for the same period in 2022.

Beginning with this announcement of first quarter 2023 financial results, Aldeyra will no longer conduct quarterly conference calls to discuss financial results. Aldeyra plans to continue hosting conference calls, as appropriate, to report the results of certain clinical trials and other material information concerning regulatory and clinical developments.

On May 4, 2023 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported business highlights and financial results for the first quarter ended March 31, 2023 (Press release, Agios Pharmaceuticals, MAY 4, 2023, View Source [SID1234630996]).

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"In the first quarter of the year, Agios made significant progress executing across our industry-leading pipeline of PK activators, with clinical studies spanning thalassemia, sickle cell disease, lower-risk MDS and pediatric PK deficiency," said Brian Goff, chief executive officer at Agios. "We closed screening of the Phase 3 studies of PYRUKYND in thalassemia with enrollment expected to be complete later this month, and look forward to the data readout of the Phase 2 portion of the RISE UP study of PYRUKYND in sickle cell disease in the middle of this year."

First Quarter 2023 & Recent Highlights

PYRUKYND U.S. Launch: Generated $5.6 million in U.S. net revenue for the first quarter of 2023, the fourth full quarter following FDA approval. A total of 127 unique patients have completed prescription enrollment forms, representing an increase of 21 percent over the fourth quarter of 2022. A total of 89 patients are on PYRUKYND therapy, representing a 14 percent increase over the fourth quarter of 2022.
Thalassemia: Closed screening of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively.
Leadership: Appointed Jeffrey Capello to the board of directors. Paul Clancy will step down from the board of directors at the end of his term, effective June 13, 2023.
Environmental, Social, and Governance (ESG): Published 2023 ESG Report, which provides corporate sustainability disclosures for the period January 1, 2022 to December 31, 2022.
Other: Servier’s Phase 3 trial of vorasidenib in patients with residual or recurrent IDH mutant low-grade glioma met both its primary endpoint and key secondary endpoints. As part of the divestiture of Agios’ oncology business to Servier, Agios retains rights to a potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales.
Key Upcoming Milestones & Priorities

Agios expects to execute on the following additional key milestones and priorities by the end of 2023:

Thalassemia: Complete enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively, by mid-year.
Sickle Cell Disease: Announce data readout from the Phase 2 portion of the RISE UP study of PYRUKYND and go/no-go to Phase 3 decision by mid-year.
Pediatric PK Deficiency: Enroll more than half of patients in the Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND by year-end.
Lower-risk Myelodysplastic Syndromes (LR-MDS): Complete enrollment of the Phase 2a study of novel PK activator AG-946 by year-end.
Pipeline: File investigational new drug (IND) application for phenylalanine hydroxylase (PAH) stabilizer for the treatment of phenylketonuria (PKU) by year-end.
First Quarter 2023 Financial Results

Revenue: Net U.S. product revenue from sales of PYRUKYND for the first quarter of 2023 was $5.6 million. This revenue reflects the fourth full quarter of PYRUKYND launch, following FDA approval on February 17, 2022.

Cost of Sales: Cost of sales for the first quarter of 2023 was $0.6 million.

Research and Development (R&D) Expenses: R&D expenses were $67.3 million for the first quarter of 2023 compared to $70.1 million for the first quarter of 2022. The year-over-year decrease was primarily driven by the $1.5 million of reimbursable transition-related expenses provided to Servier in the first quarter of 2022 related to the sale of the oncology business.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $28.4 million for the first quarter of 2023 compared to $31.5 million for the first quarter of 2022. The year-over-year decrease was primarily attributable to a reduction in workforce-related expenses.

Net Loss: Net loss was $81.0 million for the first quarter of 2023 compared to $94.8 million for the first quarter of 2022.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of March 31, 2023, were $1.0 billion compared to $1.1 billion as of December 31, 2022. Agios expects that its cash, cash equivalents and marketable securities together with anticipated product revenue and interest income will enable the company to execute its operating plan, including funding the currently planned development programs for mitapivat, AG-946 and PAH stabilization and commercializing mitapivat outside of the U.S. through one or more partnerships.

Conference Call Information
Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss first quarter 2023 financial results and recent business activities. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.