On May 4, 2023 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported financial results for the three months ended March 31, 2023, and provided an operating forecast and business updates (Press release, Ligand, MAY 4, 2023, View Source [SID1234631036]). Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time to discuss this announcement and answer questions.

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"2023 is off to a strong start with $44.0 million in first quarter revenues driven by the continued growth of our royalty revenue and the approval milestone from Travere’s FILSPARI for the treatment of IgA nephropathy," said Todd Davis, CEO of Ligand. "We have several partner catalysts this year that have the potential to further accelerate our growth for years to come. In addition to our existing portfolio, our refined corporate strategy is focused on continuing the expansion of our portfolio of late-stage partnered programs. Several initiatives are underway to increase the scale of our business development efforts related to this, with the goal of increasing the pace of investments while remaining disciplined on our capital deployment."

First Quarter 2023 Financial Results

Total revenues for the first quarter of 2023 were $44.0 million, compared with $36.5 million for the same period in 2022. Royalties for the first quarter of 2023 were $17.2 million, compared with $13.4 million for the same period in 2022, with the increase primarily attributable to Kyprolis and the growth in sales of drugs using the Pelican platform. Core Captisol sales were $10.6 million for the first quarter of 2023, compared with $6.2 million for the same period in 2022. The difference in sales was due to the timing of customer orders. There were no Captisol sales related to COVID-19 for the first quarter of 2023, compared with $5.9 million for the same period in 2022. Contract revenue was $16.2 million for the first quarter of 2023, compared with $11.0 million for the same period in 2022. The difference was due to the timing of partner milestone events.

Cost of Captisol was $3.7 million for the first quarter of 2023, compared with $4.7 million for the same period in 2022, with the decrease primarily due to lower total Captisol sales. Amortization of intangibles was $8.5 million, compared with $8.6 million for the same period in 2022. Research and development expense was $6.7 million, compared with $9.2 million for the same period in 2022, with the decrease attributed to lower stock based compensation, employee related expenses and lab supply expenses. General and administrative expense was $10.9 million, compared with $11.9 million for the same period in 2022, with the decrease primarily attributable to lower legal expenses in connection with the OmniAb spin-off.

Net income from continuing operations for the first quarter of 2023 was $43.6 million, or $2.43 per diluted share, compared with net loss from continuing operations of $12.9 million, or $0.77 per share, for the same period in 2022. Net income for the first quarter of 2023 increased due to a gain from short term investments of $39.5 million. Net loss for the first quarter of 2022 was impacted by a loss of $12.9 million from the value of Ligand’s short-term investments. Adjusted net income from continuing operations for the first quarter of 2023 was $39.9 million, or $2.28 per diluted share, compared with $11.0 million, or $0.64 per diluted share, for the same period in 2022 which excluded the impact of gross profit, net of tax, for Captisol sales related to COVID-19. See the table below for a reconciliation of net income (loss) from continuing operations to adjusted net income from continuing operations.

As of March 31, 2023, Ligand had cash, cash equivalents and short-term investments of $282.7 million.

2023 Financial Guidance

Ligand is increasing 2023 revenue and EPS guidance provided on its fourth quarter earnings call held on February 22, 2023. We now expect 2023 royalties of $78 million to $82 million (previously $74 million to $78 million), sales of Captisol of $21 million (unchanged) and contract revenue of $25 million (unchanged).These revenue components result in total revenue of $124 million to $128 million (previously $120 million to $124 million). We now expect 2023 diluted EPS of $4.60 to $4.75 (previously $3.30 to $3.45). The increase in EPS guidance is related to gains from the sale of Viking Therapeutics stock as well as the increased revenue guidance. Due to the unpredictable nature of COVID-19 and related Captisol sales, Ligand excludes Captisol for remdesivir from guidance and will update investors if and when orders are received and shipped each quarter.

First Quarter 2023 and Recent Business Highlights

Travere Therapeutics (Nasdaq: TVTX) received FDA accelerated approval for FILSPARI (sparsentan) for the treatment of IgA nephropathy (IgAN) on February 17, 2023, with commercial availability beginning in the last week of February. A review decision on sparsentan for the treatment of IgAN in Europe by the EMA is expected in the second half of 2023. On April 1, Travere announced publication in The Lancet of the interim analysis of efficacy and safety data from the ongoing pivotal, Phase 3 PROTECT Study evaluating sparsentan in adults with IgAN. The data were simultaneously presented in a late-breaking trials session at the World Congress of Nephrology 2023. On May 1, Travere announced that the pivotal Phase 3 DUPLEX Study evaluating sparsentan in focal segmental glomerulosclerosis (FSGS) did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment compared to the active control irbesartan. Secondary and topline exploratory endpoints trended favorably and a reduction of proteinuria was sustained through 108 weeks of treatment. Travere plans to engage with regulators to explore a potential path forward for sparsentan as a treatment for FSGS in the U.S. and Europe.

Viking Therapeutics (Nasdaq: VKTX) completed enrollment in its Phase 2b clinical trial of VK2809 in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) with topline data on the primary endpoint expected in 1H 2023. Separately, Ligand sold 3.2 million shares of Viking stock during the quarter resulting in $43 million of net proceeds following Viking’s announcement of positive data on their VK2735 obesity program. Ligand does not have any direct economic interest in VK2735. As of March 31, 2023, Ligand owned 3.6 million shares of VKTX stock.

Novan (Nasdaq: NOVN) submitted an NDA to the U.S. FDA seeking marketing approval for berdazimer gel, 10.3% (SB206) for the topical treatment of molluscum contagiosum. The NDA has been accepted and assigned a PDUFA date of January 5, 2024.

Palvella Therapeutics (private) announced positive topline results from its Phase 2 study of QTORIN rapamycin in microcystic lymphatic malformations; 100% of participants were rated by physicians as being "Much Improved" or "Very Much Improved" as measured on the Clinician Global Impression of Change following 12-weeks of dosing with QTORIN rapamycin. Results showed that QTORIN was generally well-tolerated with no drug-related severe adverse events. QTORIN rapamycin has the potential to become the first FDA-approved treatment for this serious, rare genetic skin disease and has been granted Fast Track and Orphan Drug Designation from the FDA for this indication. Pavella anticipates initiation of a pivotal Phase 3 study in the second half of 2023.

Novartis AG (NYSE: NVS) announced that the FDA granted approval for a liquid form of TAFINLAR (dabrafenib) + MEKINIST (trametinib) for the treatment of pediatric patients one year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation and who require systemic therapy. This is the first approval of an oral Captisol-enabled product.

Sermonix (private) announced the initiation of a registrational Phase 3 clinical study comparing targeted lasofoxifene in combination with the CDK 4/6 inhibitor abemaciclib to fulvestrant plus abemaciclib in pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation. Additionally, Sermonix announced that lasofoxifene improved vaginal/vulvar symptoms relative to fulvestrant in a study of postmenopausal women with locally advanced or metastatic estrogen receptor-positive ER+/HER2- breast cancer with an ESR1 mutation.

Anebulo Pharmaceuticals (Nasdaq: ANEB) announced completion of dosing in its randomized, double-blind, placebo-controlled, Phase 2 clinical trial evaluating ANEB-001 as a potential treatment for acute cannabinoid intoxication. The preliminary data showed ANEB-001 reduced effects of a 30 mg dose of THC, and that delayed dosing of ANEB-001 rapidly reversed pre-existing THC effects. Anebulo is targeting an End of Phase 2a meeting with FDA in the second quarter 2023.

Adjusted Financial Measures

Ligand reports adjusted net income and adjusted net income per diluted share in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The Company’s financial measures under GAAP include share-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible assets, changes in contingent liabilities, mark-to-market adjustments for amounts relating to its equity investments in public companies, excess tax benefit from share-based compensation, income tax affect of adjusted reconciling items and others that are listed in the itemized reconciliations between GAAP and adjusted financial measures included at the end of this press release. However, the Company does not provide reconciliations of such forward-looking adjusted measures to GAAP due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation, including adjustments that could be made for changes in contingent liabilities, changes in the market value of its investments in public companies, share-based compensation expense and the effects of any discrete income tax items. Management has excluded the effects of these items in its adjusted measures to assist investors in analyzing and assessing the Company’s past and future core operating performance. Additionally, adjusted earnings per diluted share is a key component of the financial metrics utilized by the Company’s board of directors to measure, in part, management’s performance and determine significant elements of management’s compensation.

Conference Call

Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (888) 350-3452 (U.S. toll-free) or 1 (646) 960-0369 (ex-U.S. toll dial-in number) using the conference ID 6501694. To participate via live or replay webcast, a link is available at www.ligand.com.

About Captisol

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Gilead Sciences’ VEKLURY, Amgen’s KYPROLIS, Baxter International’s NEXTERONE, Acrotech Biopharma L.L.C.’s and CASI Pharmaceuticals’ EVOMELA, Melinta Therapeutics’ BAXDELA and Sage Therapeutics’ ZULRESSO. There are many Captisol-enabled products currently in various stages of development. Ligand maintains a broad global patent portfolio for Captisol with approximately 390 issued patents worldwide relating to the technology (including over 40 in the U.S.) and with the latest expiration date in 2033. Other patent applications covering methods of making Captisol, if issued, extend to 2040.

About the Pelican Expression Technology Platform

Pelican is a validated, cost-effective and scalable platform for recombinant protein production that is especially well-suited for complex, large-scale protein production where traditional systems are not. Multiple global manufacturers have demonstrated consistent success with the platform and the technology is currently out-licensed for numerous commercial and development-stage programs. The versatility of the platform has been demonstrated in the production of enzymes, peptides, antibody derivatives and engineered non-natural proteins. Partners seek the platform as it can contribute significant value to biopharmaceutical development programs by reducing development timelines and costs for manufacturing therapeutics and vaccines. Given pharmaceutical industry trends toward large molecules with increasing structural complexities, Pelican is well positioned to meet these growing needs as one of the most comprehensive broadly available protein production platforms in the industry.

On May 4, 2023 Keros Therapeutics, Inc. ("Keros" or the "Company") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological, pulmonary and cardiovascular disorders with high unmet medical need, reported a business update and announced financial results for the quarter ended March 31, 2023 (Press release, Keros Therapeutics, MAY 4, 2023, View Source [SID1234631035]).

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"We are on track to report additional data from multiple clinical trials this year, including our two Phase 2 clinical trials of KER-050, one in patients with myelodysplastic syndromes ("MDS") and one in patients with myelofibrosis," said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer. "We believe these data readouts, combined with the planned commencement of our Phase 2 clinical trial of KER-012 in patients with pulmonary arterial hypertension in the first half of this year, position Keros for a year of important clinical milestones."

Recent Corporate Highlights

•Cash position strengthened: The Company has utilized its existing at the market offering to sell additional shares of common stock, which strengthened its cash position. The Company expects that its cash and cash equivalents as of March 31, 2023 will enable the Company to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025.
•Strengthened leadership with board appointment: In May 2023, Keros appointed Dr. Alpna Seth, Ph.D., to its board of directors.

Recent Program Highlights

•KER-012 for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders
◦Keros will present three poster abstracts from its KER-012 program at the American Thoracic Society ("ATS") 2023 International Conference, to be held from May 19 through May 24, 2023. The following abstracts were posted to the ATS conference website on March 2, 2023:
▪Clinical Presentation: "Administration of KER-012, a Modified Activin Receptor IIB Ligand Trap, Led to Changes in Biomarkers of Cardiovascular Health in a Ph1 Study Conducted in Healthy Post-Menopausal Women"
•Session Name: A26: Precision-Based Approaches to Pulmonary Vascular Disease
•Date and Presentation Time: May 21, 2023; 9:00 a.m. – 11:00 a.m. Eastern time
▪Preclinical Presentation: "RKER-012, a Novel Modified ActRII Ligand Trap, Attenuated Cardiac Remodeling and Fibrosis in a Transverse Aortic Constriction Model of Heart Failure"
•Session Name: A71: Matters of the Heart: Studies on Cardiopulmonary Vascular Disease
•Date and Presentation Time: May 21, 2023; 11:30 a.m. – 1:15 p.m. Eastern time
▪Preclinical Presentation: "RKER-012, a Novel Activin Receptor Type IIB (ActRIIB) Ligand Trap, Inhibited Mediators of Dysregulated Vascular Remodeling in Pulmonary Endothelial and Smooth Muscle Cells"
•Session Name: B59: Breaking Bad: New Drugs and Formulations for Pulmonary Hypertension and RV Failure
•Date and Presentation Time: May 22, 2023; 11:30 a.m. – 1:15 p.m. Eastern time

First Quarter 2023 Financial Results

Keros reported a net loss of $35.8 million in the first quarter of 2023 as compared to a net loss of $24.2 million in the first quarter of 2022. The increase of $11.6 million for the first quarter was largely due to

increased research and development efforts as well as additional investments to support the achievement of Keros’ clinical and corporate goals.

Research and development expenses were $31.1 million for the first quarter of 2023 as compared to $18.1 million for the same period in 2022. The increase of $13.0 million was primarily due to additional research and development efforts, manufacturing activities and personnel expenses to support the advancement of Keros’ pipeline.

General and administrative expenses were $7.8 million for the first quarter of 2023 as compared to $6.0 million for the same period in 2022. The increase of $1.7 million was primarily due to increase in personnel expenses and other external expenses to support Keros’ organizational growth.

Keros’ cash and cash equivalents as of March 31, 2023 was $351.4 million compared to $279.0 million as of December 31, 2022. Keros expects that the cash and cash equivalents it had on hand at March 31, 2023 will enable Keros to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025.

On May 4, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended March 31, 2023 (Press release, Karyopharm, MAY 4, 2023, View Source [SID1234631034]). In addition, Karyopharm highlighted select corporate milestones and provided an overview of its key clinical development programs.

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"We are very excited to continue advancing our pipeline in areas of high unmet need, including the rapid advancement of our myelofibrosis program. We are encouraged by the growing body of data that demonstrates the potential importance of XPO1 inhibition in patients with hard-to-treat cancers," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "In patients with treatment-naïve myelofibrosis, the combination of selinexor plus ruxolitinib produced rapid, deep and sustained spleen responses and robust symptom improvement, with response rates well above what is typically achieved with the current standard of care. Likewise, in patients with myelodysplastic neoplasms, we are encouraged with the median overall survival of 8.7 months observed with eltanexor, which is a meaningful improvement compared to the four-to-six months that is traditionally seen in patients with higher-risk relapsed or refractory MDS. Finally, in multiple myeloma, during the first quarter of 2023, we are encouraged by the year-over-year uptake of XPOVIO despite increased competition and expanded use of our patient assistance program as we continue to help additional patients gain access to treatment."

First Quarter 2023 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue for the first quarter of 2023 of $28.3 million, consistent with U.S. net product revenue in the first quarter of 2022.
Total demand1 growth driven by sales growth in the community compared to the first quarter of 2022, which contributed to about 70% of revenues in the first quarter of 2023. Sustained business in academics despite increased competition from novel bispecific and CAR-Ts.
U.S. net product revenue in the first quarter of 2023 was adversely impacted by a significant increase in utilization of the KaryForward Patient Assistance Program (free drug) due to foundations that provide financial support to patients, including Medicare patients with multiple myeloma, not having sufficient funding, and higher gross to net driven by increased Medicare rebates and 340B discounts year over year.
Continued shift of XPOVIO into earlier lines of therapy, with new patient share in second to fourth lines of therapy approaching 60% as compared to approximately 45% in the first quarter of 20222.
License agreement with the Menarini Group (Menarini) to commercialize selinexor in Europe, Latin America and other key territories expanded to include selected Middle East and Africa regions.
R&D Highlights

Myelofibrosis (MF)

Updated results from the Phase 1 study evaluating the safety and efficacy of once-weekly selinexor in combination with ruxolitinib in patients with treatment-naïve MF (NCT04562389) were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023. As of the February 24, 2023 data cut-off date, 24 patients had been assigned to either a 40mg or 60mg once weekly dose of selinexor, combined with ruxolitinib. All patients initiated treatment > 24 weeks prior to the data cut-off date. The efficacy and safety data support the 60mg dose of selinexor as the recommended dose for the Phase 3 study in combination with ruxolitinib.
Efficacy of 60mg of selinexor
83.3% and 91.7% of patients in the efficacy evaluable population demonstrated ≥35% reduction in spleen volume (SVR35) at week 12 and at week 24, respectively. In the intent to treat population, 71.4% and 78.6% of patients demonstrated an SVR35 at week 12 and at week 24, respectively.
80% and 77.8% of patients in the efficacy evaluable population evidenced a ≥50% reduction in total symptom score (TSS50) at week 12 and at week 24, respectively. In the intent to treat population, 66.7% and 58.3% of patients evidenced a TSS50 at week 12 and at week 24, respectively.
SVR35 responses were observed in 100% of evaluable patients at any time and rates were consistent regardless of subgroups, including males and patients treated with low dose ruxolitinib.
Safety of 60mg of selinexor
Selinexor was generally well tolerated and manageable, allowing most patients to remain on therapy, up to 68 weeks, as of the data cut-off date.
The most common treatment emergent adverse events (TEAEs), regardless of grade, experienced with the 60mg selinexor dose in combination with ruxolitinib were nausea (78.6%), anemia (64.3%) and fatigue (57.1%), most of which were grades 1-2.
The most common grade ≥3 TEAEs experienced with the 60mg selinexor dose in combination with ruxolitinib were anemia (42.9%), thrombocytopenia (28.6%) and neutropenia (7.1%).
Myelodysplastic Neoplasms (MDS)

Reported interim data from the Phase 2 study of single-agent eltanexor in high risk relapsed/refractory MDS (NCT02649790). As of the February 8, 2023 data cut-off date, 30 patients had been treated with 10mg eltanexor, oral, on Days 1-5 of each week. Eltanexor demonstrated a 27% overall response rate (ORR) in the intent-to-treat population and a 31% ORR in the efficacy evaluable population. Median overall survival was 8.7 months in both populations. The transfusion independence rate for red blood cells and/or platelets was 29%. The prognosis of higher risk relapsed/refractory disease is currently poor, with a median overall survival of four to six months.3,4
Eltanexor was generally well-tolerated and manageable. The most common adverse events (AEs) were asthenia (47%), diarrhea (43%), and nausea (33%), the majority of which were Grade 1-2. The most common Grade ≥3 treatment-emergent AEs were neutropenia (30%), thrombocytopenia (26.7%), and asthenia (16.7%).
Multiple Myeloma

The United Kingdom’s (UK) Medicines & Healthcare Products Regulatory Agency granted full marketing authorization for NEXPOVIO (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Stemline Therapeutics B.V., a wholly owned subsidiary of Menarini, will be responsible for all commercialization activities in the UK.
First Quarter 2023 Financial Results

Total Revenues: Total revenue for the first quarter of 2023 was $38.7 million, compared to $47.7 million for the first quarter of 2022. The decrease was due to a decline in license and other revenue.

Net product revenue: Net product revenue for the first quarter of 2023 was $28.3 million, consistent with the first quarter of 2022.

License and other revenue: License and other revenue for the first quarter of 2023 was $10.4 million, compared to $19.4 million for the first quarter of 2022. The decrease in license and other revenue in the first quarter of 2023 compared to the first quarter of 2022 was primarily due to the recognition of $7.8 million of milestone-related revenue from Antengene in the first quarter of 2022, partially offset by the recognition of $3.5 million of license- related revenue from Menarini in the first quarter of 2023. There was also a $2.3 million decrease in revenue for the reimbursement of development-related expenses from Menarini, due to a corresponding decrease in the underlying expenses.

Cost of sales: Cost of sales for the first quarter of 2023 was $1.4 million, consistent with the first quarter of 2022. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

Research and development (R&D) expenses: R&D expenses for the first quarter of 2023 were $32.3 million, compared to $42.1 million for the first quarter of 2022. The decrease in R&D expenses in the first quarter of 2023 compared to the first quarter of 2022 was primarily attributable to a decrease in clinical trial costs resulting from the prioritization of the Company’s core programs in its clinical pipeline.

Selling, general and administrative (SG&A) expenses: SG&A expenses for the first quarter of 2023 were $35.9 million, compared to $38.8 million for the first quarter of 2022.

Interest income: Interest income for the first quarter of 2023 was $2.8 million, compared to $0.1 million for the first quarter of 2022 due to higher average interest rates on investments.

Interest expense: Interest expense for the first quarter of 2023 was $5.8 million, compared to $6.7 million for the first quarter of 2022.

Net loss: Karyopharm reported a net loss of $34.1 million, or $0.30 per share, for the first quarter of 2023, compared to a net loss of $41.4 million, or $0.53 per share, for the first quarter of 2022.

Cash position: Cash, cash equivalents, restricted cash and investments as of March 31, 2023 totaled $261.9 million, compared to $279.7 million as of December 31, 2022.

2023 Financial Outlook

Based on its current operating plans, Karyopharm is updating its guidance for full year 2023:

Total revenue to be in the range of $145 million to $160 million versus previous guidance of $160 million to $175 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.
U.S. XPOVIO net product revenue to be in the range of $110 million to $125 million versus previous guidance of $125 million to $140 million, driven by the expectation that the increased use of PAP will continue in 2023, including a cumulative effect from refills.
Non-GAAP R&D and SG&A expenses*, which exclude stock-based compensation expense, to be in the range of $245 million to $260 million versus previous guidance of $260 million to $280 million, driven by accelerated closure of non-priority programs and ongoing disciplined execution.
The Company continues to expect that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into late 2025.
* Karyopharm has not reconciled the full year 2023 outlook for non-GAAP R&D and SG&A expenses to full year 2023 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2023 outlook for non-GAAP R&D and SG&A expenses.

Non-GAAP Financial Information

Karyopharm uses a non-GAAP financial measure, non-GAAP R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.

Conference Call Information

Karyopharm will host a conference call today, May 4, 2023, at 8:00 a.m. Eastern Time, to discuss the first quarter 2023 financial results and financial outlook for 2023 and to provide other business highlights. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch.

On May 4, 2023 Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, reported its financial results for the first quarter ended March 31, 2023 and provided a corporate update (Press release, Intra-Cellular Therapies, MAY 4, 2023, View Source [SID1234631033]).

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"We are pleased with the progress we have made in the first quarter and we are confident in the continued growth of CAPLYTA," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. "We are excited about our recent positive results in our clinical study in patients with mixed features in MDD and mixed features in bipolar depression. We are also encouraged by the progress we have made with our pipeline programs."

First Quarter Financial Highlights:

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Total revenues were $95.3 million for the first quarter of 2023, compared to $35.0 million for the same period in 2022. Net product sales of CAPLYTA were $94.7 million for the first quarter of 2023, compared to $34.8 million for the same period in 2022, representing a year-over-year increase of 173% and an 8% increase over the fourth quarter of 2022. First quarter CAPLYTA total prescriptions increased sequentially by 16% versus the fourth quarter of 2022.

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Net loss for the first quarter of 2023 was $44.1 million compared to a net loss of $72.1 million for the same period in 2022.

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Cost of product sales was $6.8 million in the first quarter of 2023 compared to $3.2 million for the same period in 2022.

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Selling, general and administrative (SG&A) expenses were $98.9 million for the first quarter of 2023, compared to $75.5 million for the same period in 2022. This increase is primarily due to an increase in marketing and advertising costs.

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Research and development (R&D) expenses were $38.0 million for the first quarter of 2023, compared to $29.0 million for the same period in 2022. This increase is primarily due to higher lumateperone project costs and non-lumateperone project costs.

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Cash, cash equivalents, restricted cash and investment securities totaled $540.5 million at March 31, 2023, compared to $593.7 million at December 31, 2022.

Reiterating Fiscal 2023 Financial Outlook:

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Reiterating our financial guidance for FY 2023 including CAPLYTA net product sales of $430 to $455 million.

COMMERCIAL HIGHLIGHTS

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CAPLYTA’s strong uptake continued in the first quarter of 2023 with total prescriptions increasing by 159% compared to the first quarter of 2022. First quarter CAPLYTA total prescriptions increased sequentially by 16% versus the fourth quarter of 2022.

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CAPLYTA maintained broad coverage in the Medicare Part D and Medicaid channels, with greater than 98% of lives covered and increased Commercial coverage to approximately 90% of lives covered by the end of the first quarter of 2023.

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Our LytaLink patient and prescriber support program continues to be very effective in supporting patient access to CAPLYTA.

CLINICAL HIGHLIGHTS

Lumateperone:

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Mixed Features program: Announced robust positive results from Study 403 evaluating lumateperone 42mg as monotherapy in the treatment of major depressive episodes in patients with MDD with mixed features and in patients with bipolar depression with mixed features.

In this study, lumateperone 42mg met the primary endpoint by demonstrating a statistically significant reduction in the Montgomery Asberg Depression Rating Scale (MADRS) total score compared to placebo at Week 6 in the combined patient population of MDD with mixed features and bipolar depression with mixed features (5.7 point reduction v. placebo; p<0.0001; Cohen’s d effect size (ES) of 0.64). Robust results were also seen in the individual patient population of MDD with mixed features (5.9 point reduction v. placebo; p<0.0001; ES= 0.67), and in the individual patient population of bipolar depression with mixed features (5.7 point reduction v. placebo; p<0.0001; ES= 0.64).

Lumateperone 42mg also met the key secondary endpoint in the study by demonstrating a statistically significant and clinically meaningful reduction in the clinician’s assessment of improvement in the overall severity on the Global Impression of Severity Scale (CGI-S) score compared to placebo at Week 6 in the combined patient population of MDD with mixed features and bipolar depression with mixed features (p<0.0001; ES= 0.59) and in the individual patient population of MDD with mixed features (p=0.0003; ES= 0.57), as well as the individual patient population of bipolar depression with mixed features p<0.0001; ES=0.61). Lumateperone was generally safe and well tolerated, with a side effect profile consistent with prior lumateperone trials.

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Adjunctive MDD program: Lumateperone is in Phase 3 clinical development as a novel treatment for MDD. Patient enrollment in Study 501 and Study 502, global Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD, is ongoing. In addition, we recently initiated a third global Phase 3 trial, Study 505, also evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD. Subject to the results of Studies 501 and 502, we expect to file a supplemental New Drug Application with the FDA in 2024 for approval of lumateperone as an adjunctive therapy to antidepressants for the treatment of MDD.

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Lumateperone Long Acting Injectable (LAI) formulation: The goal of our program is to develop LAI formulations that are effective, safe and well-tolerated with treatment durations of one month or longer. We are undertaking Phase 1 single ascending dose studies with several formulations in 2023 and next year.

Other pipeline programs:

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ITI-1284-ODT-SL program: ITI-1284 is a deuterated form of lumateperone, a new chemical entity formulated as an oral disintegrating tablet for sublingual administration. We plan to initiate Phase 2 programs in agitation in patients with Alzheimer’s disease (AD), in psychosis in patients with AD and in generalized anxiety disorder in 2023.

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Phosphodiesterase type I inhibitor (PDE1) program: Our portfolio of PDE1 inhibitors is being developed to treat diseases in which PDE1 activity is over active.

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Lenrispodun (ITI-214) is our lead PDE1 inhibitor compound. Patient enrollment in a Phase 2 clinical trial in Parkinson’s disease (PD) commenced in the first quarter of 2023. The objective of this proof-of-concept study is to evaluate improvements in motor symptoms in patients with PD. Changes in cognition and inflammatory biomarkers will also be assessed.

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ITI-1020 is our second drug candidate in our PDE1 inhibitor program. We have an active Investigational New Drug application to evaluate ITI-1020 as a novel cancer immunotherapy. We have commenced a Phase 1 program in healthy volunteers.

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ITI-333 program: ITI-333, a 5-HT2A receptor antagonist and µ-opioid receptor partial agonist, provides potential utility in the treatment of opioid use disorder, pain and mood disorders. We have two ongoing studies: a multiple ascending dose study in healthy volunteers evaluating pharmacokinetics, safety and tolerability and a neuroimaging study.

Conference Call and Webcast Details

The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. To attend the live conference call by phone please use this registration link (View Source). All participants must use the link to complete the online registration process in advance of the conference call.

The live and archived webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.intracellulartherapies.com. Please log in approximately 5-10 minutes prior to the event to register and to download and install any necessary software.

CAPLYTA (lumateperone) is indicated in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.

Important Safety Information

Boxed Warnings:

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Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

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Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.

Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

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Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.

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Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.

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Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.

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Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.

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Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.

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Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.

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Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.

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Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

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Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.

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Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.

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Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.

Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors.

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Dose reduction is recommended for patients with moderate or severe hepatic impairment.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.

CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules.

Please click here to see full Prescribing Information including Boxed Warning.

About CAPLYTA (lumateperone)

CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Lumateperone is being studied for the treatment of major depressive disorder, and other neuropsychiatric and neurological disorders. Lumateperone is not FDA-approved for these disorders.

On May 4, 2023 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, reported operational highlights and financial results for the first quarter ended March 31, 2023 (Press release, Intellia, MAY 4, 2023, View Source [SID1234631032]).

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"We’ve had a productive start to the year with the successful clearance of our first IND application for an investigational in vivo CRISPR-based therapy alongside broad pipeline and platform progress," said Intellia President and Chief Executive Officer John Leonard, M.D. "Today, we are pleased to announce dosing has begun in the Phase 2 study of NTLA-2002, and based on strong interest from investigators and patients, we expect to complete enrollment in the second half of this year. Our rapid progression of the clinical development of NTLA-2002 supports our goal to bring forth a potential functional cure for the treatment of hereditary angioedema. Simultaneously, we are working toward submitting our second in vivo IND application and initiating a global pivotal trial for NTLA-2001. We look forward to sharing new interim data from both the NTLA-2001 and NTLA-2002 first-in-human studies in the months to come."

First Quarter 2023 and Recent Operational Highlights

In Vivo Program Updates

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is an in vivo, systemically delivered, investigational CRISPR-based therapy designed to inactivate the TTR gene in liver cells and thereby prevent the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. NTLA-2001 is subject to a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc.
ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
Intellia plans to submit a U.S. Investigational New Drug (IND) application in mid-2023. Subject to regulatory feedback, the Company anticipates initiating a global pivotal trial for ATTR-CM by year-end 2023.
The Company expects to present additional data from the ATTR-CM arm of the Phase 1 study in 2023, including longer-term safety and durability data, as well as emerging clinical endpoints.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
As previously announced, during the first quarter of 2023, the planned enrollment of the dose-expansion portion of the ATTRv-PN arm in the Phase 1 study was completed to inform a pivotal study. The Company is actively preparing for a global pivotal study, which includes discussions with regulatory authorities.
Intellia recently began redosing patients in the 0.1 mg/kg cohort (n=3), the initial cohort and lowest dose tested in the dose-escalation portion of the Phase 1 study, with the 55 mg dose selected for the dose-expansion cohort.
The Company plans to present additional clinical data from the ATTRv-PN arm of the Phase 1 study in 2023.
Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 is a wholly owned, in vivo, systemically delivered investigational CRISPR-based therapy. NTLA-2002 is designed to knock out the KLKB1 gene in the liver, with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous reduction of plasma kallikrein activity, following a single dose. It also aims to eliminate the significant treatment burden associated with currently available HAE therapies. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE.
Intellia announced today that the first patient has been dosed in the global Phase 2 portion of its Phase 1/2 clinical trial of NTLA-2002. Based on encouraging study interest from both investigators and patients, the Company expects to complete enrollment (n=25) in 2H 2023.
The Company announced in March that the U.S. Food and Drug Administration (FDA) cleared the NTLA-2002 Phase 2 IND application. Additionally, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to NTLA-2002 for the treatment of HAE.
In January 2023, Intellia was awarded the Innovation Passport for NTLA-2002 by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA). The Innovation Passport is the point of entry into the U.K.’s Innovative Licensing and Access Pathway (ILAP), which is designed to accelerate time to market and facilitate patient access to innovative medicines.
The Company plans to present additional clinical data from the Phase 1 portion of the first-in-human study in 2023. Data expected to be presented include updated safety, durability of pharmacodynamic effect and attack-rate measures from all three patient cohorts.
Alpha-1 Antitrypsin Deficiency (AATD)

NTLA-3001 for Associated Lung Disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to improve patient outcomes, including eliminating the need for weekly intravenous infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia is conducting IND-enabling activities for NTLA-3001 and plans to submit an IND or IND-equivalent filing in 2H 2023.
NTLA-2003 for Associated Liver Disease: NTLA-2003 is a wholly owned, in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.
Intellia is conducting IND-enabling activities for NTLA-2003, with the expectation of completing these activities by year-end 2023.
Ex Vivo Program Updates

Immuno-oncology and Autoimmune Diseases

Intellia is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.
Board of Directors Update: In April, Intellia announced the appointment of Bill Chase to its board of directors. Mr. Chase will be a member of the audit committee and will succeed Caroline Dorsa as chair of the audit committee upon her retirement from the board on June 15, 2023.
Corporate Responsibility Report: In May, Intellia published its 2023 Corporate Responsibility Report. The report highlights the Company’s Environmental, Social and Governance (ESG) principles and practices as part of its objective to build a sustainable company while delivering on its commitments to patients, employees and shareholders.
Upcoming Events

The Company will participate in the following events during the second quarter of 2023:

Bank of America Securities 2023 Health Care Conference, May 9, Las Vegas
2023 RBC Capital Markets Global Healthcare Conference, May 16, New York City
Barclays Gene Editing & Therapy Summit, May 24, New York City
Stifel Genetic Medicines Day, May 30, virtual
Upcoming Milestones

The Company has set forth the following expected milestones for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Submit an IND application in mid-2023 to enable inclusion of U.S. sites in a pivotal study of NTLA-2001 for patients with ATTR-CM.
Present additional clinical data from the ongoing Phase 1 study of NTLA-2001 in 2023.
Initiate a global pivotal NTLA-2001 trial for ATTR-CM by year-end 2023, subject to regulatory feedback.
Prepare for a Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN, including discussions with regulatory authorities.
NTLA-2002 for HAE:
Present additional clinical data from the ongoing first-in-human study of NTLA-2002 in 2023.
Complete enrollment in the Phase 2 portion of the Phase 1/2 study in 2H 2023.
AATD Franchise:
Submit an IND or IND-equivalent application for NTLA-3001 for AATD-associated lung disease in 2H 2023.
Complete IND-enabling activities for NTLA-2003 for AATD-associated liver disease by year-end 2023.
Platform Innovation:
Advance novel gene editing technologies, including DNA writing and delivery to other tissues outside of the liver.
First Quarter 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.2 billion as of March 31, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of approximately $120.9 million. The decrease was offset in part by $12.0 million of interest income, $3.4 million of reimbursement from its collaborators, $1.5 million of net equity proceeds from the Company’s "At the Market" (ATM) program and $0.8 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue increased by $1.3 million to $12.6 million during the first quarter of 2023, compared to $11.3 million during the first quarter of 2022.
R&D Expenses: Research and development expenses decreased by approximately $36.0 million to $97.1 million during the first quarter of 2023, compared to $133.1 million during the first quarter of 2022. This decrease was primarily driven by $56.0 million of expense related to the acquisition of Rewrite Therapeutics, Inc. during the first quarter of 2022. The decrease related to the acquisition of Rewrite Therapeutics, Inc. was offset by an increase in expenses of $20.0 million primarily driven by the advancement of its lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $16.9 million for the first quarter of 2023.
G&A Expenses: General and administrative expenses increased by $5.0 million to $27.4 million during the first quarter of 2023, compared to $22.4 million during the first quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $2.1 million. Stock-based compensation expense included in general and administrative expenses was $10.3 million for the first quarter of 2023.
Net Loss: The Company’s net loss was $103.1 million for the first quarter of 2023, compared to $146.9 million during the first quarter of 2022.
Conference Call to Discuss First Quarter 2023 Results

The Company will discuss these results on a conference call today, Thursday, May 4, at 8 a.m. ET.
To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on May 4, at 12 p.m. ET.