On February 23, 2023 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the fourth quarter and full year ended December 31, 2022 and provided a corporate update (Press release, Arvinas, FEB 23, 2023, View Source [SID1234627597]).

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"2022 was an exciting year for Arvinas as we transitioned into a late-stage development organization and laid the foundation for an important year of data readouts and trial initiations in 2023," said John Houston, Ph.D., president and chief executive officer at Arvinas. "Notably, the initiation of our Phase 3 monotherapy trial with ARV-471 in ER+/HER2- metastatic breast cancer marks our first registrational study and if successful, will lead to our first commercial product bringing an important new treatment option to patients. We are on-track to initiate our second and third Phase 3 trials – one in the first line setting with ARV-471 and one with bavdegalutamide in metastatic castrate resistant prostate cancer – in the second half of this year, further validating our novel PROTAC discovery engine platform."

Recent Developments and 4Q Business Highlights

Gained alignment with FDA on an approach to the planned 1L Phase 3 trial with ARV-471 in combination with palbociclib to enable trial initiation in 2H 2023
The approach includes a Phase 3 lead-in to evaluate the optimal dose of palbociclib (100 mg or 75 mg) in combination with 200 mg ARV-471
The approach follows the recent analysis of data from the ongoing Phase 1b combination study of ARV-471 with palbociclib, in which an increase in palbociclib exposure was observed relative to historical palbociclib pharmacokinetic data
Initiated the VERITAC-2 Phase 3 2L+ clinical trial of ARV-471 as a monotherapy for the treatment of patients with ER+/HER2- metastatic breast cancer
Presented results from the Phase 2 cohort expansion portion (VERITAC) of a Phase 1/2 study with ARV-471 for the treatment of ER+/HER2- metastatic breast cancer
Initiated two arms of a Phase 1b umbrella trial with ARV-471; one in combination with ribociclib and another with abemaciclib (TACTIVE-U)
Initiated a Phase 2 trial with ARV-471 as a monotherapy in the neoadjuvant setting (TACTIVE-N)
Presented new preclinical neuroscience data at Society for Neuroscience’s "Neuroscience 2022" meeting demonstrating cross-species oral bioavailability and biodistribution into deep brain regions of nonhuman primates
Disclosed a BCL6 (B-cell lymphoma 6) PROTAC degrader in oncology and a LRRK2 (leucine-rich repeat kinase 2) PROTAC degrader in neuroscience as the Company’s next IND or CTA submissions
Appointed Everett Cunningham to the Company’s Board of Directors
Anticipated Upcoming Milestones and Expectations

ARV-471
With Pfizer, the companies plan to:

Initiate a Phase 3 trial with ARV-471 + palbociclib as a first-line treatment in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H 2023)
Initiate additional arms of the Phase 1b combination umbrella trial (TACTIVE-U) with other targeted therapies (2023)
Provide an update with preliminary data from the Phase 1b combination trial with palbociclib (1H 2023)
Submit and present data from the Phase 1b combination trial with palbociclib at a medical congress (2H 2023)
AR Franchise (Bavdegalutamide/ARV-110, ARV-766)

Initiate a global Phase 3 trial with confirmed bavdegalutamide dose in metastatic castration-resistant prostate cancer (mCRPC) for patients with AR T878/H875 tumor mutations (2H 2023)
Complete enrollment in the Phase 1b combination study with bavdegalutamide plus abiraterone (2H 2023)
Share Phase 1 dose escalation trial data with ARV-766 in mCRPC (2Q 2023)
Initiate a Phase 1b or Phase 2 trial in patients who have not previously received novel hormonal agents (2H 2023)
Pipeline:

Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology) and LRRK2 (neuroscience) PROTAC protein degraders by year-end 2023
Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of December 31, 2022, is sufficient to fund planned operating expenses and capital expenditure requirements into 2026.

Full Year and Fourth Quarter Financial Results

Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of December 31, 2022, cash, cash equivalents, restricted cash and marketable securities were $1,210.8 million, as compared with $1,507.1 million as of December 31, 2021. The decrease in cash, cash equivalents, restricted cash and marketable securities of $296.3 million for the year was primarily related to cash used in operations of $279.2 million (net of $6.5 million received from two collaborators), unrealized loss on marketable securities of $14.6 million, loss on the sales of securities of $0.4 million and the purchase of lab equipment and leasehold improvements of $6.8 million, partially offset by proceeds from the exercise of stock options of $4.7 million.

Research and Development Expenses: Research and development expenses were $315.0 million and $98.3 million for the year and quarter ended December 31, 2022, as compared with $180.4 million and $61.8 million for the year and quarter ended December 31, 2021. The increase in research and development expenses of $134.6 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $77.7 million, our AR program (which includes bavdegalutamide (ARV-110) and ARV-766) of $15.7 million and our ER program of $41.2 million, which is net of the cost sharing of ARV-471 under the global Pfizer collaboration agreement to develop and commercialize ARV-471 that was initiated in July 2021 (ARV-471 Collaboration Agreement). The increase in research and development expenses of $36.5 million for the quarter was primarily due to an increase in expenses associated with our platform and exploratory programs of $24.9 million, our AR program of $5.5 million and our ER program of $6.0 million.

General and Administrative Expenses: General and administrative expenses were $79.6 million and $15.1 million for the year and quarter ended December 31, 2022, as compared with $61.6 million and $18.9 million for the year and quarter ended December 31, 2021. The increase in general and administrative expenses of $18.0 million for the year was primarily due to an increase of personnel related costs of $15.0 million and professional fees of $5.6 million. The decrease in general and administrative expenses of $3.8 million for the quarter was primarily due to a decrease in facility costs attributable to our general and administrative functions.

Revenue: Revenue was $131.4 million and $38.0 million for the year and quarter ended December 31, 2022 as compared with $53.6 million and $28.7 million for the year and quarter ended December 31, 2021. Revenue is related to the ARV-471 Collaboration Agreement with Pfizer that was initiated in July 2021, the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017 and revenue related to our Oerth Bio joint venture which was initiated in July 2019. The increase in revenues of $77.8 million and $9.3 million for the year and quarter was primarily due to revenues from the ARV-471 Collaboration Agreement with Pfizer.

Income Tax Expense: Income tax expense was $20.9 million and $10.8 million for the year and quarter ended December 31, 2022, as compared with zero for the year and quarter ended December 31, 2021 due to taxable income projected for fiscal year 2022 primarily related to revenue recognized in 2022 for tax purposes from the ARV-471 Collaboration Agreement.

Loss from Equity Method Investment: Loss from equity method investment totaled $10.6 million and $3.0 million for the year and quarter ended December 31, 2022, compared with $6.9 million and $2.3 million for the year and quarter ended December 31, 2021 due to increased operating losses incurred by Oerth Bio.

Net Loss: Net loss was $282.5 million and $82.9 million for the year and quarter ended December 31, 2022, as compared with $191.0 million and $52.9 million for the year and quarter ended December 31, 2021. The increase in net loss for the year and quarter was primarily due to increased research and development expenses, general and administrative expenses and losses from equity investment, partially offset by increased revenue.

About bavdegalutamide (ARV-110)
Bavdegalutamide (ARV-110) is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

Bavdegalutamide has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade AR. In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer, and ARV-766 may also have applicability in other AR-driven diseases both in and outside oncology. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.

On February 23, 2023 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the fourth quarter and full year ended December 31, 2022 and reviewed recent business highlights (Press release, Alnylam, FEB 23, 2023, View Source [SID1234627596]).

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"2022 was another year of strong progress at Alnylam, including our continued commercial execution which delivered 35% full-year product revenue growth (43% with constant exchange rate*) compared to 2021. A key factor in these results was the approval and launch of AMVUTTRA, which is off to a great start in its first two full quarters on the market. Further to our leadership in TTR amyloidosis, we’re thrilled to have submitted our sNDA for ONPATTRO for the treatment of the cardiomyopathy of ATTR amyloidosis, which has now been accepted by the FDA, and look forward to potentially bringing this important therapy to patients, if approved," said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. "Looking ahead to 2023, we are excited for a number of important milestones across the pipeline, with 10 clinical readouts from proprietary and partner-led programs, including first-in-human results for an RNAi therapeutic in the CNS from our Phase 1 study of ALN-APP, as well as Phase 2 results from the KARDIA studies of zilebesiran. With the totality of this progress, we believe we are on track to achieve our Alnylam P5x25 goals and position Alnylam as a top-tier biotech company poised to deliver sustainable innovation."

Fourth Quarter 2022 and Recent Significant Corporate Highlights

Commercial Performance

Total TTR: ONPATTRO (patisiran) & AMVUTTRA (vutrisiran)

Achieved global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter of $122 million and $69 million, respectively, representing 12% total TTR quarterly growth compared to Q3 2022, and full year 2022 revenues of $558 million and $94 million, respectively, representing 37% total TTR annual growth compared to full year 2021.
Attained over 2,975 hATTR amyloidosis patients with polyneuropathy worldwide on commercial treatment with ONPATTRO or AMVUTTRA as of December 31, 2022, up from over 2,580 commercial patients as of September 30, 2022, representing 15% total TTR quarterly growth and 46% total TTR annual growth vs. 2021.
Received 760 Start Forms in the U.S. for AMVUTTRA from launch through December 31, 2022, with ~53% representing new patients and ~47% representing patients switching from ONPATTRO.
GIVLAARI (givosiran)

Achieved global net product revenues for the fourth quarter and full year 2022 of $47 million and $173 million, respectively, representing quarterly and annual growth of 3% and 35% compared to Q3 2022 and full year 2021, respectively.
Attained over 520 patients worldwide on commercial GIVLAARI treatment as of December 31, 2022, up from over 460 commercial patients as of September 30, 2022, representing 13% quarterly growth and 47% annual growth vs. 2021.
OXLUMO (lumasiran)

Achieved global net product revenues for the fourth quarter and full year 2022 of $24 million and $70 million, respectively, representing quarterly and annual growth of 45% and 17% compared to Q3 2022 and full year 2021, respectively.
Attained over 280 patients worldwide on commercial OXLUMO treatment as of December 31, 2022, up from over 230 commercial patients as of September 30, 2022, representing 22% quarterly growth and 101% annual growth vs. 2021.
Leqvio (inclisiran)

Launch is ongoing, with focus on patient on-boarding, removing access hurdles and enhancing medical education.
R&D Highlights

Patisiran (the non-proprietary name for ONPATTRO), in development for the treatment of ATTR amyloidosis.

Submitted and received acceptance of the sNDA for ONPATTRO (patisiran) for the treatment of the cardiomyopathy of ATTR amyloidosis. The FDA has set an action date of October 8, 2023 under the Prescription Drug User Fee Act (PDUFA).
In their file acceptance letter, the FDA stated that they have not identified any review issues. The Agency also noted that they are planning to hold an advisory committee meeting to discuss the application.
Vutrisiran (the non-proprietary name for AMVUTTRA), in development for the treatment of ATTR amyloidosis.

Announced topline results from the Randomized Treatment Extension (RTE) of the HELIOS-A Phase 3 study evaluating a biannual dosing regimen of vutrisiran.
Non-inferiority of 50 mg biannual (vs. 25 mg quarterly) was established, as measured by TTR lowering through nine months in the RTE, along with an acceptable safety profile.
However, the Company announces its strategic decision not to proceed with regulatory submissions for a biannual dosing regimen of vutrisiran and instead will focus on advancing ALN-TTRsc04, which has now entered the clinic and offers the potential for more durable and potent TTR silencing via annual dosing.
Received approval from the Brazilian Health Regulatory Agency (ANVISA) for AMVUTTRA for the treatment of hATTR amyloidosis in adults.
Lumasiran (the non-proprietary name for OXLUMO), for the treatment of primary hyperoxaluria type 1 (PH1).

Based on the successful outcome of the ILLUMINATE-C study in children and adults with advanced PH1, received approval from the U.S. FDA of an sNDA for OXLUMO, expanding the indication for the treatment of PH1 to lower urinary oxalate and plasma oxalate levels in pediatric and adult patients, and received approval from the European Medicines Agency (EMA) of a Type II variation to include the ILLUMINATE-C data in the label.
Inclisiran (the non-proprietary name for Leqvio), for the treatment of hypercholesterolemia or mixed dyslipidemia, in collaboration with Novartis.

New long-term data from the ORION-3 open-label study demonstrated effective and sustained reductions in LDL cholesterol over four years of treatment. At any time throughout the trial, approximately 80% of patients reached an LDL-C level of <70mg/dL. Data presented at AHA 2022.
Early- and mid-stage investigational RNAi therapeutic pipeline programs and RNAi platform.

Completed enrollment in the KARDIA-1 Phase 2 monotherapy study of zilebesiran in patients with mild-to-moderate hypertension.
Submitted Clinical Trial Authorization (CTA) filings for ALN-KHK for the treatment of type 2 diabetes, and ALN-PNP for the treatment of NASH in collaboration with Regeneron. Regeneron announced that dosing in a Phase 1 study of ALN-PNP has been initiated.
Submitted a CTA application for ALN-TTRsc04, in development for the treatment of ATTR amyloidosis. The Company announces today that dosing in a Phase 1 study has been initiated.
Announced pipeline prioritization decisions at 2022 R&D Day, including discontinuation of ALN-XDH in gout and lumasiran in recurrent renal stones, and pausing development of cemdisiran in IgA nephropathy.
Additional Business Updates

Appointed Carolyn Bertozzi, Ph.D. to its Board of Directors. Also, Amy W. Schulman, previously the Lead Independent Director, assumed the role of Chair of the Board from Michael W. Bonney, who has continued on the Board as a non-independent director. Mr. Bonney stepped down from his interim role as Executive Chair.
Ranked #1 on The Boston Globe’s 2022 list of Great Places to Work in the "Largest Employer category.
Ranked #2 in Science Magazine’s 2022 Top Employer survey, marking the fourth year Alnylam was featured as one of the top three companies.
Recognized on Newsweek’s 2023 list of America’s Most Responsible Companies.
Upcoming Events

In early 2023:

Alnylam intends to complete enrollment in the KARDIA-2 Phase 2 study of zilebesiran.
Alnylam intends to report preliminary topline results from the Phase 1 study of ALN-APP in patients with early onset Alzheimer’s Disease.
Alnylam intends to initiate a Phase 1 study of ALN-KHK in normal healthy volunteers.
Vir intends to report additional results from Part A of the MARCH trial evaluating the combination of ALN-HBV02 (VIR-2218) and VIR-3434, an anti-HBV monoclonal antibody, for the treatment of patients with chronic HBV infection in the first half of 2023.
Vir also plans to report additional results from a Phase 2 study evaluating the combination of ALN-HBV02 (VIR-2218) and PEG-IFN alpha in the first half of 2023.
Regeneron plans to initiate a Phase 2 study of ALN-HSD in patients with NASH.
Financial Results for the Quarter and Year Ended December 31, 2022

Financial Highlights

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(In thousands, except per share amounts)

2022

2021

2022

2021

Net product revenues

$

261,675

$

198,514

$

894,329

$

662,138

Net revenue from collaborations

$

70,645

$

59,625

$

134,912

$

180,953

Royalty revenue

$

2,715

$

396

$

8,177

$

1,196

GAAP Operating loss

$

(188,614

)

$

(194,561

)

$

(785,072

)

$

(708,652

)

Non-GAAP Operating loss

$

(145,847

)

$

(149,979

)

$

(554,423

)

$

(542,935

)

GAAP Other expense, net

$

(18,407

)

$

(65,741

)

$

(341,921

)

$

(143,492

)

Non-GAAP Other expense, net

$

(25,203

)

$

(60,163

)

$

(232,023

)

$

(199,187

)

GAAP Net loss

$

(207,493

)

$

(258,460

)

$

(1,131,156

)

$

(852,824

)

Non-GAAP Net loss

$

(171,522

)

$

(208,300

)

$

(790,609

)

$

(742,802

)

GAAP Net loss per common share – basic and diluted

$

(1.68

)

$

(2.16

)

$

(9.30

)

$

(7.20

)

Non-GAAP Net loss per common share – basic and diluted

$

(1.39

)

$

(1.74

)

$

(6.50

)

$

(6.27

)

Net Product Revenues

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(In thousands)

2022

2021

2022

2021

ONPATTRO net product revenues

$

122,221

$

138,630

$

557,608

$

474,737

AMVUTTRA net product revenues

68,566

93,795

Total TTR net product revenues

190,787

138,630

651,403

474,737

GIVLAARI net product revenues

47,058

40,679

173,144

127,815

OXLUMO net product revenues

23,830

19,205

69,782

59,586

Total net product revenues

$

261,675

$

198,514

$

894,329

$

662,138

Year over Year % Growth

Three Months Ended
December 31,

Twelve Months Ended
December 31,

As
Reported

At CER*

As
Reported

At CER*

Total TTR net product revenues

38%

48%

37%

46%

GIVLAARI net product revenues

16%

22%

35%

41%

OXLUMO net product revenues

24%

33%

17%

25%

Total net product revenues

32%

41%

35%

43%

* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the three and twelve months ended December 31, 2021. CER is a Non-GAAP measure.

Net product revenues increased 32% and 35% at actual currency during the three and twelve months ended December 31, 2022, respectively, compared to the same periods in 2021, and 41% and 43% at CER, respectively. The increases are primarily due to increased patients on our commercial TTR products as well as increased patients on GIVLAARI and OXLUMO.
Net Revenues from Collaborations

Net revenues from collaborations increased 18% during the fourth quarter 2022, as compared to the prior year, primarily due to increased revenue from our collaboration with Regeneron from increased manufacturing activities.
Net revenues from collaborations decreased 25% for the twelve months ended December 31, 2022, as compared to the prior year, primarily due to a decrease in revenue recognized in connection with our collaboration agreements with Regeneron and Vir, attributed to reduced research and manufacturing activities and timing of reimbursable activities.
Operating Expenses

Three Months Ended
December 31,

Twelve Months Ended
December 31,

(in thousands)

2022

2021

2022

2021

GAAP research and development expenses

$

262,039

$

229,050

$

883,015

$

792,156

Non-GAAP research and development expenses

$

245,095

$

210,513

$

790,854

$

723,741

GAAP selling, general and administrative expenses

$

210,344

$

186,382

$

770,658

$

620,639

Non-GAAP selling, general and administrative expenses

$

184,521

$

160,337

$

632,170

$

523,337

Research & Development (R&D) Expenses

GAAP and non-GAAP R&D expenses increased during the three and twelve months ended December 31, 2022, compared to the same periods in 2021, primarily due to increases in headcount to support our R&D pipeline, development expenses associated with the KARDIA-1 and KARDIA-2 zilebesiran Phase 2 studies, and manufacturing and research related expenses associated with our pre-clinical and developmental activities. GAAP R&D expenses further increased during the twelve month period due to increased stock-based compensation expense related to the accounting for certain performance-based awards that vested during the period.
Selling, General & Administrative (SG&A) Expenses

GAAP and non-GAAP SG&A expenses increased during the three and twelve months ended December 31, 2022, compared to the same periods in 2021, primarily due to increased headcount and other strategic investments in support of the global launch of AMVUTTRA and other expenses to support our strategic growth. GAAP SG&A expenses further increased during the twelve month period due to stock-based compensation expense related to the accounting for certain performance-based awards that vested during the period.
Other Financial Highlights

GAAP other expense, net, decreased during the fourth quarter 2022, as compared to the prior year, primarily due to foreign currency gains as a result of the U.S. Dollar weakening against key global currencies, increased interest income, and unrealized gains on marketable equity securities.
GAAP other expense, net, increased during the twelve months ended December 31, 2022, compared to the same period in 2021, primarily due to a loss on the extinguishment of the Blackstone credit agreement, increased realized and unrealized losses on our marketable equity securities, and an increased loss from the fair value adjustment on the development derivative liability, offset by an increase in interest income.
Cash, cash equivalents and marketable securities were $2.19 billion as of December 31, 2022 compared to $2.44 billion as of December 31, 2021 with the decrease primarily due to our year-to-date operating loss in 2022. This decrease was largely offset by approximately $265 million received from employee option award exercises and approximately $135 million received from the issuance of convertible debt, net of repayment borrowings, inclusive of prepayment premiums under the credit facility, the purchase of capped call transactions, and underwriter fees.
The adjustments to the non-GAAP measures provided in the financial results above and in the financial guidance below are described under "Use of Non-GAAP Financial Measures" later in this press release. A reconciliation of our GAAP to non-GAAP results presented in this release is included in the tables of this press release.

2023 Financial Guidance1

Full year December 31, 2023 financial guidance consists of the following:

Combined net product revenues for ONPATTRO, AMVUTTRA, GIVLAARI and OXLUMO1,2

$1,200 million – $1,285 million

Net Product Revenue Growth vs. 2022 at reported Fx rates1

34% to 44%

Net Product Revenue Growth vs. 2022 at constant exchange rates*

34% to 44%

Net revenues from collaborations and royalties

$100 million – $175 million

GAAP R&D and SG&A expenses

$1,790 million – $1,885 million

Non-GAAP R&D and SG&A expenses3

$1,575 million – $1,650 million

1 Uses December 31, 2022 Fx rates including: 1 EUR = 1.07 USD and 1 USD = 131 JPY

2 Assumes U.S. sNDA approval of patisiran for ATTR amyloidosis with cardiomyopathy by the PDUFA date on October 8, 2023

3 Excludes $215-$235 million of stock-based compensation expense from estimated GAAP R&D and SG&A expenses

* CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in the twelve months ended December 31, 2022. CER is a Non-GAAP measure.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses and non-recurring gains and expenses outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses, realized and unrealized (gains) losses on marketable equity securities and loss on the extinguishment of debt. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the realized and unrealized (gains) losses on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company’s ongoing operations for the period in which such gains or losses are reported, as their sole purpose is to adjust amounts on the balance sheet. The Company has excluded the loss on the extinguishment of debt because the Company believes the item is a non-recurring transaction outside the ordinary course of the Company’s business.

Percentage changes in revenue growth at CER, also a non-GAAP financial measure, are presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. The current period’s foreign currency revenue values are converted into U.S. dollars using the average exchange rates from the prior period.

The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between historical GAAP and non-GAAP measures presented in this release is provided later in this press release.

Conference Call Information

Management will provide an update on the Company and discuss fourth quarter and year-end 2022 results as well as expectations for the future via conference call on Thursday, February 23, 2023 at 8:30 am ET. To access the call, please register online at https://register.vevent.com/register/BI050ad56309204f0a836ec037dd396473. Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months.

A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events. An archived webcast will be available on the Alnylam website approximately two hours after the event.

On February 23, 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 fourth quarter and year ended Dec. 31, 2022 (Press release, Agios Pharmaceuticals, FEB 23, 2023, View Source [SID1234627595]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"Over the past year, Agios has made significant progress toward our vision of transforming the lives of patients with rare diseases as we build a hematology franchise focused on diseases that share a common underlying pathophysiology, limited treatment options and profound unmet need," said Brian Goff, chief executive officer at Agios. "In 2022, we received regulatory approvals in the U.S., EU and Great Britain for PYRUKYND as the first and only disease-modifying treatment for adults with pyruvate kinase (PK) deficiency. We achieved our ambitious enrollment targets for our pivotal trials in thalassemia and sickle cell disease. We strengthened our company leadership with the appointments of new management team and Board members with deep expertise in rare diseases and global commercial strategy. We are poised for significant near- and long-term growth and look forward to a productive 2023, anticipating the readout of our Phase 2 sickle cell disease study and the completion of enrollment in our Phase 3 thalassemia studies, driving toward two additional PYRUKYND indications by 2026."

Fourth Quarter 2022 & Recent Highlights

PYRUKYND U.S. Launch: Continued to execute launch, generating $4.3 million in U.S. net revenue for the fourth quarter of 2022, the third full quarter following FDA approval. A total of 105 unique patients have completed prescription enrollment forms, representing an increase of 25 percent over the third quarter. A total of 78 patients are on PYRUKYND therapy, representing a 39 percent increase over the third quarter.
PYRUKYND Global Approvals: Received marketing authorization for adults with PK deficiency in the EU and Great Britain.
Sickle Cell Disease: Completed enrollment in the Phase 2 portion of the RISE UP study of PYRUKYND in adults with sickle cell disease.
Thalassemia: Enrolled more than half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively.
Data Presentations: Presented broad set of clinical and translational data at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, including long-term PYRUKYND data in adults with non-transfusion-dependent thalassemia and in adults with PK deficiency.
Leadership: Appointed Tsveta Milanova to the role of chief commercial officer, bringing two decades of experience in rare disease commercial strategy and global market access.
Anticipated 2023 Milestones

Thalassemia: Complete enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND by mid-year.
Sickle Cell Disease: Announce data readout from the Phase 2 portion of the RISE UP study of PYRUKUND 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.
Fourth Quarter 2022 Financial Results

The financial results discussion compares Agios’ continuing operations. All periods have been adjusted to exclude discontinued operations related to the divested oncology business.

Revenue: Net U.S. product revenue from sales of PYRUKYND was $4.3 million for the fourth quarter of 2022, and $11.7 million for the full year ended Dec. 31, 2022. PYRUKYND was approved by the FDA on February 17, 2022.

Cost of Sales: Cost of sales was $0.4 million for the fourth quarter of 2022 and $1.7 million for the full year ended Dec. 31, 2022.

Non-Operating Income: Non-operating income included $127.9 million as gain on sale of contingent payments from the sale of TIBSOVO royalty rights to Sagard Healthcare Partners. Non-operating income also included approximately $9.9 million from TIBSOVO royalties for the full year ended Dec. 31, 2022, with royalty income ceasing after the third quarter of 2022 due to the sale of these rights to Sagard.

Research and Development (R&D) Expenses: R&D expenses were $70.3 million for the fourth quarter of 2022 compared to $73.3 million for the fourth quarter of 2021, and $279.9 million for the year ended Dec. 31, 2022 compared to $257.0 million for the year ended Dec. 31, 2021. The year-over-year increase in R&D expense was primarily driven by increased costs for PYRUKYND and AG-946 studies and increased workforce spend across R&D.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $32.8 million for the fourth quarter of 2022 compared to $31.5 million for the fourth quarter of 2021, and $121.7 million for the year ended Dec. 31, 2022 compared to $121.4 million for the year ended Dec. 31, 2021.

Net Income (Loss) from Continuing Operations: Net income was $36.5 million for the fourth quarter of 2022 compared to a net loss of $98.6 million for the fourth quarter of 2021, and net loss was $231.8 million for the year ended Dec. 31, 2022 compared to $356.5 million for the year ended Dec. 31, 2021.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of Dec. 31, 2022, were $1.1 billion compared to $1.3 billion as of Dec. 31, 2021. This cash position includes the receipt of a one-time payment of $131.8 million associated with the sale of our rights to 5% royalties on U.S. net sales of Servier’s TIBSOVO. 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, to cash-flow positivity without the need to raise additional equity.

Conference Call Information
Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and year end 2022 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.

On February 23, 2023 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the fourth quarter and full year of 2022 and provided a corporate update (Press release, Aclaris Therapeutics, FEB 23, 2023, View Source [SID1234627594]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"The past year for Aclaris was marked by tremendous execution across our organization notably highlighted by our clinical development programs and our proprietary kinase-focused drug discovery platform," stated Doug Manion, M.D., Chief Executive Officer of Aclaris. "We enter 2023 well positioned to capitalize on that momentum with multiple data read-outs expected, beginning with top line data from the Phase 2a trial of zunsemetinib in hidradenitis suppurativa next month."

Continued Dr. Manion, "In addition to the enthusiasm related to our upcoming development-stage milestones, we also continue to benefit from the output of our KINect discovery engine, and the ability to identify novel development candidates, which we believe will not only position us to continue to build long-term shareholder value, but also enable us to further fulfill our mission of delivering new therapeutic options for patients."

Research and Development Highlights:

Clinical Development Programs:

• Zunsemetinib, an investigational oral small molecule MK2 inhibitor:
Currently being developed as a potential treatment for immuno-inflammatory diseases

Rheumatoid Arthritis (ATI-450-RA-202): This Phase 2b dose ranging trial to investigate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses (20 mg and 50 mg twice daily) of zunsemetinib in combination with methotrexate in subjects with moderate to severe rheumatoid arthritis (RA) is ongoing. Aclaris expects topline data in the second half of 2023.

Hidradenitis Suppurativa (ATI-450-HS-201): This Phase 2a trial to investigate the efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg twice daily) over 12 weeks in subjects with moderate to severe hidradenitis suppurativa (HS) has completed enrollment with 95 patients randomized and is ongoing. Aclaris expects topline data in March of 2023.

Psoriatic Arthritis (ATI-450-PsA-201): This Phase 2a trial to investigate the efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg twice daily) in subjects with moderate to severe psoriatic arthritis (PsA) is ongoing. Aclaris expects topline data by year end 2023.

• ATI-1777, an investigational topical "soft" Janus kinase (JAK) 1/3 inhibitor:
Currently being developing as a potential treatment for moderate to severe atopic dermatitis (AD)

Atopic Dermatitis (ATI-1777-AD-202): This Phase 2b trial to determine the efficacy, safety, tolerability, and PK of multiple doses and application regimens of ATI-1777 in subjects with moderate to severe AD is ongoing. Aclaris expects topline data mid-year 2023.
• ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor:
Currently being developed as a potential treatment for T cell-mediated autoimmune diseases

Aclaris has selected ulcerative colitis as the intended first clinical development target for ATI-2138. Aclaris is also exploring additional indications that are relevant to the mechanism of action.

Aclaris initiated a Phase 1 MAD (multiple ascending dose) trial of ATI-2138 in healthy volunteers in December of 2022. Aclaris expects topline data from the MAD trial in the second half of 2023.
Preclinical Development Program

• ATI-2231, an investigational oral MK2 inhibitor compound:
Currently being explored as a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer

Second MK2 inhibitor generated from Aclaris’ proprietary KINect drug discovery platform and designed to have a long plasma half-life.

Aclaris expects clinical development activities to be initiated in 2023, which is expected to advance as a collaboration with an academic third party.
Financial Highlights:

Liquidity and Capital Resources

As of December 31, 2022, Aclaris had aggregate cash, cash equivalents and marketable securities of $229.8 million compared to $225.7 million as of December 31, 2021. Aggregate cash, cash equivalents and marketable securities as of December 31, 2022 included proceeds received during the fourth quarter under a license agreement with Pediatrix Therapeutics, Inc. (Pediatrix).

Aclaris continues to anticipate that its cash, cash equivalents and marketable securities as of December 31, 2022 will be sufficient to fund its operations through the end of 2025, without giving effect to any potential business development transactions or financing activities.

Financial Results

Fourth Quarter 2022

Net loss was $27.6 million for the fourth quarter of 2022 compared to $22.8 million for the fourth quarter of 2021.

Total revenue was $7.8 million for the fourth quarter of 2022 compared to $1.5 million for the fourth quarter of 2021. The increase was driven by $6.7 million of licensing revenue in the quarter, including $5 million from the license agreement with Pediatrix.

Research and development (R&D) expenses were $21.1 million for the quarter ended December 31, 2022 compared to $14.1 million for the prior year period.
The $7.0 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS, and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and costs associated with a Phase 2b clinical trial for AD.
ATI-2138 development expenses, including costs associated with a Phase 1 SAD trial, a Phase 1 MAD trial, and other preclinical activities.
Compensation-related expenses due to an increase in headcount.
General and administrative (G&A) expenses were $7.1 million for the quarter ended December 31, 2022 compared to $6.9 million for the prior year period.

Licensing expenses were $0.6 million for the quarter ended December 31, 2022 resulting primarily from obligations to the former Confluence equity holders from revenue generated from the Pediatrix license agreement. There were no licensing expenses for the quarter ended December 31, 2021.

Revaluation of contingent consideration was $7.1 million for the quarter ended December 31, 2022, compared to a revaluation of contingent consideration expense of $2.2 million for the prior year period.
Full Year 2022

Net loss was $86.9 million for the year ended December 31, 2022 compared to $90.9 million for the year ended December 31, 2021.

Total revenue was $29.8 million for the year ended December 31, 2022 compared to $6.8 million for the year ended December 31, 2021.
The $23.0 million increase was driven by a $24.3 million increase in licensing revenue during 2022, which included $17.6 million of upfront and milestone payments received under the non-exclusive patent license agreement with Eli Lilly and a $5.0 million upfront payment received under the Pediatrix license agreement. The increase in licensing revenue was offset by a decrease in contract research revenues.
R&D expenses were $77.8 million for the year ended December 31, 2022 compared to $43.8 million for the prior year period.
The $34.0 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS, and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and costs associated with a Phase 2b clinical trial for AD.
ATI-2138 development expenses, including costs associated with a Phase 1 SAD trial, a Phase 1 MAD trial, and other preclinical activities.
ATI-2231 preclinical development expenses associated with preclinical activities and IND-enabling studies.
Compensation-related expenses due to an increase in headcount.

Licensing expenses were $7.9 million for the year ended December 31, 2022 resulting from separate third-party contractual obligations primarily related to the non-exclusive patent license agreement with Eli Lilly. There were no licensing expenses for the year ended December 31, 2021.

G&A expenses were $25.1 million for the year ended December 31, 2022 compared to $23.6 million for the prior year period.
The $1.5 million increase was primarily the result of higher stock-based compensation and personnel costs due to an increase in headcount.
Revaluation of contingent consideration charges related to the Confluence acquisition was $4.7 million for the year ended December 31, 2022 compared to $24.3 million for the prior year period.

On February 23, 2023 AbbVie (NYSE: ABBV) and Capsida Biotherapeutics Inc. ("Capsida") reported an expanded strategic collaboration to develop genetic medicines for eye diseases with high unmet need (Press release, AbbVie, FEB 23, 2023, View Source [SID1234627593]). AbbVie’s extensive capabilities will be paired with Capsida’s novel adeno-associated virus (AAV) engineering platform and manufacturing capability to identify and advance three programs. The collaboration builds upon the neurodegenerative disease partnership announced in 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"This expanded collaboration with Capsida has the potential to develop transformative therapies for patients with serious eye diseases," said Jonathon Sedgwick, Ph.D., vice president and global head of discovery research, AbbVie. "In pursuing the promise of genetic medicine-based therapeutics, AbbVie continues to expand our capabilities, and we are pleased to have Capsida as a partner."

"AbbVie has been an excellent partner, and we are excited to expand our collaboration into ophthalmology with the world leader in this therapeutic area," said Peter Anastasiou, chief executive officer of Capsida. "Combining AbbVie’s expertise in eye disease drug development and commercialization with Capsida’s fully integrated next-generation AAV engineering platform and manufacturing capabilities offers the potential to provide novel therapies enabling unprecedented benefit to patients with serious eye diseases."

Under the terms of the expanded agreement, Capsida will receive $70 million, consisting of upfront payments and a potential equity investment. For the three programs, Capsida may be eligible to receive up to $595 million in option fees and research and development milestones, with potential for further commercial milestones. Capsida is also eligible to receive mid-to-high single-digit royalty payments on future product sales. Capsida will lead capsid discovery efforts for all programs using its high throughput AAV engineering platform and will be responsible for process development and early clinical manufacturing. AbbVie will lead innovative therapeutic cargo approaches and be responsible for development and commercialization.