On August 3, 2023 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) [("Merrimack" or the "Company")] reported its second quarter 2023 financial results for the period ended June 30, 2023 (Press release, Merrimack, AUG 3, 2023, View Source [SID1234633754]).

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"We were excited to see the announcement from Ipsen that the U.S. Food and Drug Administration (FDA) had accepted its supplemental new drug application (sNDA) Onivyde (irinotecan liposome injection) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX regimen) as a potential first-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC) and that the FDA had provided a Prescription Drug User Fee Act goal date of 13 February 2024 for review of the application" said Gary Crocker, Chairman of Merrimack’s Board of Directors. "We will continue to monitor the progress of this program which, if approved, would entitle Merrimack to a $225 million milestone payment from Ipsen."

Second Quarter 2023 Financial Results

Merrimack reported a net loss of $391 thousand for the second quarter ended June 30, 2023, or $0.03 per basic and diluted share on a fully diluted basis, compared to a net loss of $478 thousand, or $0.04 per basic and diluted share on a fully diluted basis, for the same period in 2022.

Interest income in the second quarter ended June 30, 2023, was $178 thousand compared to $8 thousand for the same period in 2022.

General and administrative expenses for the second quarter ended June 30, 2023, were $569 thousand, compared to $486 thousand for the same period in 2022.

As of June 30, 2023, Merrimack had cash, cash equivalents and short term investments of $19.0 million, compared to $19.4 million as of December 31, 2022.

As of June 30, 2023, Merrimack had 14.3 million shares of common stock outstanding.

Updates on Programs Underlying Potential Milestone Payments

Ipsen

Metastatic Pancreatic Ductal Adenocarcinoma

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In November 2022, Ipsen announced the Phase III NAPOLI 3 trial of Onivyde (irinotecan liposome injection) plus 5-fluorouracil/leucovorin and oxaliplatin (the "NALIRIFOX regimen") met its primary endpoint demonstrating clinically meaningful and statistically significant improvement in overall survival compared to nab-paclitaxel plus gemcitabine in 770 previously untreated patients with mPDAC and key secondary efficacy outcome of progression-free survival (PFS) also showed significant improvement over the comparator arm. Ipsen also announced that the safety profile of Onivyde in the NAPOLI 3 trial was consistent with those observed in the previous phase I/II mPDAC study.

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In January 2023, Ipsen presented clinical trial results at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.

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In June 2023, Ipsen announced that the U.S. Food and Drug Administration (FDA) had accepted its supplemental new drug application (sNDA) Onivyde (irinotecan liposome injection) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX regimen) as a potential first-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC) and that the FDA had provided a Prescription Drug User Fee Act goal date of 13 February 2024 for review of the application.

Small Cell Lung Cancer

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In August 2022, Ipsen announced that the Phase III RESILIENT trial did not meet its primary endpoint of overall survival compared to topotecan. The trial is evaluating Onivyde versus topotecan in patients with small cell lung cancer, who have progressed on or after platinum-based first-line therapy treatment. In the announcement, Ipsen indicated that detailed results from the RESILIENT trial would be presented at an upcoming medical conference. The analysis concluded that the primary endpoint overall survival was not met in patients treated with Onivyde versus topotecan. However, a doubling of the secondary endpoint of objective response rate in favor of Onivyde was observed. In the August 2022 announcement, Ipsen reported that the clinical study results would be communicated with the regulatory agency. Ipsen indicated that while the results from the analysis of the RESILIENT trial have not demonstrated an overall survival benefit with Onivyde in patients in second-line small cell lung cancer, Ipsen intends to analyze the data further before decisions regarding next steps are made.

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To date, there have been no further announcements by Ipsen regarding these matters and it remains unclear as to whether Ipsen will continue to seek approval for the use of Onivyde in the small cell lung cancer application. If Ipsen elects not to proceed with seeking regulatory approval, or if regulatory approval is not obtained, Merrimack would not be entitled to the $150 million milestone payment tied to FDA approval of Onivyde for treatment of small cell lung cancer.

Elevation Oncology

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In January 2023, Elevation announced it is pausing further investment in the clinical development of seribantumab and intends to pursue further development only in collaboration with a partner. If Elevation elects not to proceed with seeking regulatory approval, or if regulatory approval is not obtained, Merrimack would not be entitled to the $54.5 million in additional potential development, regulatory approval and commercial-based milestone payments.

On August 3, 2023 Pharma major Lupin Limited [BSE: 500257 | NSE: LUPIN] reported its financial performance for the quarter ending June 30, 2023 (Press release, Lupin, AUG 3, 2023, View Source [SID1234633753]). These unaudited results were taken on record by the Board of Directors at a meeting held today.

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Financial Highlights – Consolidated IND-AS

Amt in INR mn

Particulars Quarter
Q1 FY2024 Q4 FY2023 QoQ Growth % Q1 FY2023 YoY Growth %
Sales 47,421 43,303 ↑9.5% 36,040 ↑31.6%
EBITDA 8,791 6,150 ↑ 42.9% 2,379 ↑ 269.6%
EBITDA Margin (%) 18.5% 14.2% ↑ 430 bps 6.6% ↑ 1190 bps
PBT 5,588 2,585 ↑116.2% 23 ↑24516.3%
Income Statement highlights – Q1 FY2024

Gross Profit was INR 31,013 mn compared to INR 25,803 mn in Q4 FY2023, with gross margin of 65.4%
Personnel cost was 17.8% of sales at INR 8,444 mn compared to INR 7,730 mn in Q4 FY2023
Manufacturing and other expenses were 31.0% of sales at INR 14,724 mn compared to INR 13,030 mn in Q4 FY2023
Investment in R&D for the quarter was INR 3,679 mn (7.8% of sales)
Balance Sheet highlights

Operating working capital was INR 51,946 mn as on June 30, 2023
Capital Expenditure for the quarter was INR 1,171 mn
Net Debt as on June 30, 2023 stands at INR 13,099 mn
Net Debt-Equity as on June 30, 2023 stands at 0.10
Commenting on the results, Mr. Nilesh Gupta, Managing Director, Lupin Limited said, "Building on the momentum of the last few quarters, we had a strong quarter with good growth across all key markets as we continue to improve our operating margins driven by higher sales, better mix and cost optimization initiatives. Our India branded business has bounced back to double-digit growth despite NLEM price reductions. With the clearance of Pithampur Unit-2 we expect to add to the product approvals for the US region. Getting approvals for important complex generics like Tiotropium DPI, and getting back into the launch tempo with first to market products like Darunavir and additional new product launches will help sustain the growth momentum both in topline and bottom line as we move ahead"

Consolidated Financial Results Q1 FY2024

Amt in INR mn

Particulars Q1 FY2024 % of sales Q4 FY2023 % of sales QoQ Gr% Q1 FY2023 % of sales YoY Gr%
Sales 47,421 100.0% 43,303 100.0% 9.5% 36,040 100.0% 31.6%
Other operating income 720 1.5% 998 2.3% -27.9% 1,398 3.9% -48.5%
Total Revenue from operations 48,141 101.5% 44,301 102.3% 8.7% 37,438 103.9% 28.6%
Material cost 16,408 34.6% 17,501 40.4% -6.2% 16,098 44.7% 1.9%
Gross Profit (Excl. Other op. income) 31,013 65.4% 25,802 59.6% 20.2% 19,942 55.3% 55.5%
Employee cost 8,444 17.8% 7,730 17.9% 9.2% 7,785 21.6% 8.5%
Manufacturing & Other expenses 14,724 31.0% 13,030 30.1% 13.0% 11,916 33.1% 23.6%
Other Income 228 0.5% 373 0.9% -38.9% 56 0.2% 307.1%
Forex Loss / (Gain) 2 0.0% 263 0.6% -99.3% (684) -1.9% -100.3%
EBITDA 8,791 18.5% 6,150 14.2% 42.9% 2,379 6.6% 269.5%
Depreciation, Amortization & Impairment Expense 2,346 4.9% 2,640 6.1% -11.1% 1,928 5.3% 21.7%
EBIT 6,445 13.6% 3,510 8.1% 83.6% 451 1.3% 1329.0%
Finance cost 857 1.8% 925 2.1% -7.4% 428 1.2% 100.2%
Profit Before Tax (PBT) 5,588 11.8% 2,585 6.0% 116.2% 23 0.1% 24516.3%
Tax 1,055 2.2% 161 0.4% 891 2.5%
Profit After Tax (PAT) 4,533 9.6% 2,424 5.6% (868) -2.4%
(+) Share of Profit from JV – – – – – –
(-) Non-Controlling Interest 10 0.0% 64 0.1% 23 0.1%
Profit/(Loss) for the period 4,523 9.5% 2,360 5.4% (891) -2.5%

Sales Mix

Amt in INR mn

Particulars Q1 FY2024 Q4 FY2023 Growth QoQ Q1 FY2023 Growth YoY
North America 15,905 15,503 2.6% 10,104 57.4%
India 16,384 14,786 10.8% 14,920 9.8%
Growth Markets 4,066 4,385 -7.3% 4,237 -4.0%
EMEA 3,987 4,535 -12.1% 3,335 19.6%
ROW 1,655 868 90.6% 893 85.3%
Total Formulations 41,997 40,077 4.8% 33,489 25.4%
API 3,371 3,226 4.5% 2,551 32.1%
Total Product Sales 45,368 43,303 4.8% 36,040 25.9%
NCE Income 2,053 – NA – NA
Consolidated Sales 47,421 43,303 9.5% 36,040 31.6%

Operational Highlights

North America

North America sales for Q1 FY2024 were INR 15,905 mn, up 2.6% compared to INR 15,503 mn in Q4 FY2023; up 57.4% as compared to INR 10,104 mn in Q1 FY2023; and accounted for 34% of Lupin’s global sales.

Q1 FY2024 sales were USD 181 mn compared to USD 175 mn in Q4 FY2023 and USD 121 mn in Q1 FY2023.

The Company received 4 ANDA approvals from the U.S. FDA, and launched 3 products in the quarter in the U.S. The Company now has 158 generic products in the U.S.

Lupin continues to be the 3rd largest pharmaceutical player in both U.S. generic market and U.S. total market by prescriptions (IQVIA MAT June 2023). Lupin is the leader in 41 of its marketed generics in the U.S. and amongst the Top 3 in 109 of its marketed products (IQVIA March 2023).

India

India formulation sales for Q1 FY2024 were INR 16,384 mn, up 10.8% as compared to INR 14,786 mn in Q4 FY2023; up 9.8% as compared to INR 14,920 mn in Q1 FY2023; and accounted for 35% of Lupin’s global sales.

India Region Formulations sales grew by 11.6% in the quarter as compared to Q4 FY2023, up 10.6% as compared to Q1 FY2023. The company launched 4 brands across therapies during the quarter.

Lupin is the 6th largest company in the Indian Pharmaceutical Market (IQVIA MAT June 2023).

Growth Markets (LATAM and APAC)

Growth Markets registered sales of INR 4,066 mn for Q1 FY2024, down 7.3% compared to INR 4,385 mn in Q4 FY2023; down 4.0% as compared to INR 4,237 mn in Q1 FY2023; and accounted for 9% of Lupin’s global sales.

Brazil sales were BRL 75 mn for Q1 FY2024, compared to BRL 75 mn for Q4 FY2023 and BRL 57 mn for Q1 FY2023.

Mexico sales were MXN 86 mn for Q1 FY2024, compared to MXN 152 mn for Q4 FY2023 and MXN 213 mn for Q1 FY2023.

Philippines sales were PHP 463 mn for Q1 FY2024, compared to PHP 542 mn for Q4 FY2023 and PHP 434 mn for Q1 FY2023.

Australia sales were AUD 26 mn for Q1 FY2024, compared to AUD 24 mn for Q4 FY2023 and AUD 25 mn for Q1 FY2023.

Europe, Middle-East and Africa (EMEA)

EMEA sales for Q1 FY2024 were INR 3,987 mn, down 12.1% compared to INR 4,535 mn in Q4 FY2023; up 19.6% compared to INR 3,335 mn in Q1 FY2023; and accounted for 8% of Lupin’s global sales.

South Africa sales were ZAR 295 mn for Q1 FY2024, compared to ZAR 417 mn for Q4 FY2023 and ZAR 282 mn for Q1 FY2023. Lupin is the 8th largest player in South Africa in the total generics market (IQVIA May 2023).

Germany sales were EUR 10 mn for Q1 FY2024, compared to EUR 10 mn for Q4 FY2023 and EUR 9 mn for Q1 FY2023.

Global API

Global API Sales for Q1 FY2024 were INR 3,371 mn, up 4.5% as compared to INR 3,226 mn in Q4 FY2023; up 32.1% as compared to INR 2,551 mn in Q1 FY2023; and accounted for 7% of Lupin’s global sales.

Research and Development

Investment in R&D was INR 3,679 mn (7.8% of sales) for Q1 FY2024 as compared to INR 3,050 mn (7.0% of sales) for Q4 FY2023.

Lupin received approval for 4 ANDAs from the U.S. FDA in the quarter. Cumulative ANDA filings with the U.S. FDA stand at 443 as of June 30, 2023, with the company having received 294 approvals to date.

The Company now has 54 First-to-File (FTF) filings including 21 exclusive FTF opportunities. Cumulative U.S. DMF filings stand at 169 as of June 30, 2023.

On August 3, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported second quarter 2023 financial results and provided a corporate update (Press release, Kura Oncology, AUG 3, 2023, View Source [SID1234633752]).

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"With its safety, tolerability and clinical activity profile, we believe ziftomenib has the ideal properties to become part of the backbone of acute myeloid leukemia (AML) therapy across the continuum of patient care," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Our confidence in the program is strengthened by the late-breaking clinical data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June, which showed one of the highest response rates reported for a targeted therapy in the setting of relapsed/refractory AML. Building on momentum generated by these data, enrollment in our Phase 2 registration-directed trial of ziftomenib in patients with relapsed/refractory NPM1-mutant AML continues to outperform our projections, an indication of both the size of this population and its significant unmet need. In addition, we are now treating NPM1-mutant and KMT2A-rearranged AML patients with ziftomenib in combination with chemotherapy- and venetoclax-based regimens, and we look forward to sharing preliminary data from this first combination study later this year or early next."

Recent Highlights

Late-breaking clinical data for ziftomenib in NPM1-mutant AML – In June, Kura reported updated data from the KOMET-001 trial of ziftomenib, including durable activity in patients with heavily pretreated and co-mutated relapsed/refractory NPM1-mutant AML. The data were featured during a late-breaking oral session at the EHA (Free EHA Whitepaper) Annual Congress in Frankfurt. As of an April 12th data cutoff, seven of the 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (RP2D) of 600 mg achieved complete remission (CR) with full count recovery, for a CR rate of 35% and an overall response rate of 45%. An eighth patient, who had a CR with partial count recovery after treatment with ziftomenib, subsequently evolved to a CR with full count recovery after stem cell transplant and remained on study as of the EHA (Free EHA Whitepaper) presentation. In addition, a patient with NPM1-mutant AML treated at 200 mg remained on ziftomenib for 36 cycles as of the cutoff date. The median duration of response for all NPM1-mutant patients was 8.2 months, with a median follow-up of 8.8 months. Continuous once-daily dosing of ziftomenib was well tolerated in the Phase 1 trial and the reported adverse event profile remained consistent with features of underlying disease.

Enrollment in registration-directed trial of ziftomenib continues to outperform projections – Enrollment in Kura’s Phase 2 registration-directed trial of ziftomenib in NPM1-mutant relapsed or refractory AML continues to outperform the Company’s projections. The trial is expected to enroll a total of 85 patients in the U.S. and Europe, with a primary endpoint of CR or CR with partial hematologic recovery (CRh). NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists.

Multiple patients dosed in combination study of ziftomenib in NPM1-mutant and KMT2A-rearranged AML – Kura is conducting a series of studies to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations. The Company is now dosing patients in the first of its combination studies, KOMET-007, in patients with NPM1-mutant and KMT2A-rearranged AML in the newly diagnosed and relapsed/refractory settings. KOMET-007 is a Phase 1 study designed to assess safety, tolerability and preliminary activity of ziftomenib in combination with venetoclax/azacitidine (ven/aza) or standard induction cytarabine/daunorubicin chemotherapy (7+3). Kura anticipates having preliminary data from the KOMET-007 study in the fourth quarter of 2023 or first quarter of 2024.

Continued evidence of clinical activity observed with tipifarnib plus alpelisib in PIK3CA-dependent HNSCC – Previously, Kura reported the first demonstration of a durable clinical response with the combination of its farnesyl transferase inhibitor (FTI) tipifarnib and the PI3K alpha inhibitor alpelisib in PIK3CA-mutant head and neck squamous cell carcinoma (HNSCC). In the meantime, dose escalation in the Company’s KURRENT-HN trial of tipifarnib and alpelisib has continued, with ongoing evidence of clinical activity at multiple doses and no dose-limiting toxicities to date. Kura is now evaluating patients in the trial’s highest planned dose cohort to inform selection of the optimal biologically active dose for the combination, after which the Company intends to initiate a small dose expansion of patients with PIK3CA-mutant HNSCC to validate the safety profile and activity of the combination at the RP2D. Head and neck cancer is the seventh most common cancer worldwide and remains a significant unmet need, with no approved small molecule targeted therapies.

First-in-human study of KO-2806 to begin in second half of 2023 – KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. Earlier this year, Kura received FDA clearance of its Investigational New Drug application for KO-2806. Site activation has now begun in a Phase 1 dose-escalation trial of KO-2806 (FIT-001) and the Company expects to dose the first patients in the second half of 2023. Concurrent with dose escalation as a monotherapy, Kura also plans to evaluate KO-2806 in dose escalation combination cohorts in advanced solid tumors, beginning with clear cell renal cell carcinoma (ccRCC).
Financial Results

Research and development expenses for the second quarter of 2023 were $28.2 million, compared to $24.3 million for the second quarter of 2022.

General and administrative expenses for the second quarter of 2023 were $11.8 million, compared to $11.1 million for the second quarter of 2022.

Net loss for the second quarter of 2023 was $37.2 million, compared to a net loss of $34.8 million for the second quarter of 2022. This includes non-cash share-based compensation expense of $7.0 million, compared to $6.5 million for the same period in 2022.

As of June 30, 2023, Kura had cash, cash equivalents and short-term investments of $477.0 million, compared to $438.0 million as of December 31, 2022. This includes net proceeds of approximately $93.6 million from the Company’s public offering completed in June 2023.

Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations to mid-2026.
Forecasted Milestones

Dose the first patients in the KOMET-008 trial of ziftomenib in combination with additional standards of care, including the FLT3 inhibitor gilteritinib, in the second half of 2023.

Preliminary data from the KOMET-007 trial of ziftomenib in combination with ven/aza or 7+3 in the fourth quarter of 2023 or first quarter of 2024.

Dose the first patients in the ziftomenib post-transplant maintenance program in the first quarter of 2024.

Initiate dose expansion in the KURRENT-HN trial of tipifarnib and alpelisib in mid-2024.

Dose the first patients in the FIT-001 monotherapy dose-escalation trial of KO-2806 as a monotherapy in the second half of 2023.

Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with a targeted therapy in ccRCC in the second half of 2024.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, August 3, 2023, to discuss the financial results for the second quarter 2023 and to provide a corporate update. The live call may be accessed by dialing (888) 886-7786 for domestic callers and (416) 764-8658 for international callers and entering the conference ID: 26884460. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

On August 3, 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 second quarter ended June 30, 2023 and provided a corporate update (Press release, Intra-Cellular Therapies, AUG 3, 2023, View Source [SID1234633751]).

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"Our continued commercial execution resulted in another quarter of solid growth for CAPLYTA. Due to CAPLYTA’s strong performance to date and our confidence in continued growth, we are raising our 2023 full year net product sales guidance," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. "We have also continued to progress our pipeline including our clinical and preclinical development programs."

Second Quarter Financial Highlights:

Total revenues were $110.8 million for the second quarter of 2023, compared to $55.6 million for the same period in 2022. Net product sales of CAPLYTA were $110.1 million for the second quarter of 2023, compared to $55.1 million for the same period in 2022, representing a year-over-year increase of 100% and a 16% sequential increase over the first quarter of 2023.

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Net loss for the second quarter of 2023 was $42.8 million compared to a net loss of $86.6 million for the same period in 2022.

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Cost of product sales was $7.2 million in the second quarter of 2023 compared to $4.7 million for the same period in 2022.

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Selling, general and administrative (SG&A) expenses were $101.0 million for the second quarter of 2023, compared to $100.3 million for the same period in 2022.

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Research and development (R&D) expenses were $49.8 million for the second quarter of 2023, compared to $38.5 million for the same period in 2022. This increase is primarily due to higher lumateperone project costs.

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Cash, cash equivalents, restricted cash and investment securities totaled $514.6 million at June 30, 2023.

Fiscal 2023 Financial Outlook:

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Full year 2023 CAPLYTA net product sales guidance increased to $445 to $465 million from the previous range of $430 to $455 million.

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Full year 2023 SG&A expense guidance of $420 to $450 million and R&D expense guidance of $195 to $220 million reiterated.

CLINICAL HIGHLIGHTS

Lumateperone:

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Adjunctive Major Depressive Disorder (MDD) program: Patient enrollment is ongoing in Studies 501, 502 and 505, our global Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD.

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Mixed Features program: Last quarter, we 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. These strong results reaffirm lumateperone’s efficacy and safety profile and highlight its potential across mood disorders. We plan to present data from Study 403 at upcoming major psychiatry meetings in the second half of 2023.

We also conducted an important post-hoc analysis of a pre-specified patient population in Study 403 evaluating the antidepressant effects of lumateperone in patients with mixed features exhibiting anxious distress, commonly known as anxious depression. In patients meeting the DSM-5 criteria for anxious distress at study entry, lumateperone significantly improved on the Montgomery Asberg Depression Rating Scale (MADRS) total score compared with placebo in the combined MDD and bipolar depression mixed features population with anxious distress. The MADRS mean difference vs. placebo was -6.1 points, with a robust effect size of -0.67 with a p value of less than <0.0001. Robust results were also seen in each individual patient population of patients with MDD and patients with bipolar depression. The strong results seen in this analysis further strengthen our confidence in CAPLYTA’s potential as a treatment for MDD.

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Lumateperone Long Acting Injectable (LAI) formulation: We expect to initiate Phase 1 single ascending dose studies with several formulations of our LAI later in 2023, and expect these studies to continue through 2024. The goal of the program is to develop LAI formulations that are effective, safe, and well-tolerated with treatment durations of one month or longer.

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Presentations and Publications: In the second quarter of 2023, there were CAPLYTA presentations at several medical meetings including the American Psychiatric Association (APA), the International Society for Bipolar Disorders (ISBD), and the American Society of Clinical Psychopharmacology (ASCP). The presentations primarily highlighted important aspects of CAPLYTA’s clinical profile in both the acute and the long-term treatment of a broad patient population with bipolar I and bipolar II disorder as monotherapy and as adjunctive therapy.

The article, "The Efficacy of Lumateperone in Patients With Bipolar Depression With Mixed Features (McIntyre RS, et al 2023) was published in the Journal of Clinical Psychiatry. The authors of this post hoc analysis of Study 404 concluded that lumateperone 42mg significantly improved symptoms of depression and disease severity in patients with a major depressive episode associated with bipolar I or bipolar II disorder, with or without mixed features.

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 generalized anxiety disorder, in psychosis in patients with Alzheimer’s disease (AD), and in agitation in patients with AD in 2023.

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Phosphodiesterase type I inhibitor (PDE1) program: We continue to develop our portfolio of PDE1 inhibitors:

Lenrispodun (ITI-214) Parkinson’s disease (PD) program: Patient enrollment in our Phase 2 clinical trial is ongoing. The objective of this study is to evaluate improvements in motor symptoms in patients with PD. Changes in cognition and inflammatory biomarkers are also being assessed.

ITI-1020 cancer immunotherapy program: Our Phase 1 single ascending dose study in healthy volunteers is ongoing. The objective of this study is to evaluate pharmacokinetics, safety, and tolerability of different doses of ITI-1020.

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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 and pain. We have completed the single ascending dose study and a multiple ascending dose study and a positron emission tomography (PET) study are ongoing.

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ITI-1500 Non-Hallucinogenic Psychedelic Program: This program is focused on the development of novel non-hallucinogenic psychedelics. Compounds in this series interact with serotonergic (5-HT2a) receptors in a unique way, potentially allowing the development of this new drug class in mood, anxiety and other neuropsychiatric disorders without the liabilities of known psychedelics including the hallucinogenic potential and risk for cardiac valvular pathologies. Our lead compound in this program, ITI-1549, is currently being evaluated in IND enabling studies.

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 (https://register.vevent.com/register/BI096f6f0766f746f592599ba0431eda8c). 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. 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 August 3, 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 second quarter ended June 30, 2023 (Press release, Intellia, AUG 3, 2023, View Source [SID1234633750]).

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"We continue to make significant and rapid progress in the development of our first two in vivo, CRISPR-based therapeutic candidates," said Intellia President and Chief Executive Officer John Leonard, M.D. "For NTLA-2002, we are thrilled to see the excitement for this investigational therapy from the HAE community. In just a handful of months, we were able to identify all patients required to fully enroll the ongoing Phase 2 study and now expect to initiate the pivotal Phase 3 program next year. For NTLA-2001, our team has been working diligently to prepare for an IND submission in September and to begin the Phase 3 study for the cardiomyopathy manifestation of ATTR amyloidosis before the end of this year. Overall, we continue to believe that NTLA-2001 and NTLA-2002 represent only the beginning for our pipeline and platform as additional in vivo and ex vivo candidates advance toward the clinic."

Second 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 an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in September. Subject to regulatory feedback, the Company anticipates initiating a global pivotal study for ATTR-CM by year-end 2023.
The Company expects to present additional data from the ATTR-CM arm of the Phase 1 study by year-end 2023, including longer-term safety and durability data, as well as emerging clinical endpoints.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
The Company is actively preparing for a global pivotal Phase 3 study, including discussions with regulatory authorities.
The Company plans to present additional data from the ATTRv-PN arm of the Phase 1 study by year-end 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 due to the substantial interest from physicians and patients to participate in the NTLA-2002 clinical program, all patients have been identified for the global Phase 2 portion of the study with enrollment expected to be completed in the second half of 2023.
Based on the strong momentum of the program, the Company plans to complete enrollment at ex-U.S. sites in the ongoing Phase 2 study. Further, following the March 2023 IND clearance, the FDA requested supplemental preclinical data related to the inclusion of female patients of child-bearing potential. Intellia expects to submit these data in advance of the planned Phase 3 trial, which will complement the clinical data collected from female patients of child-bearing potential dosed in the ongoing Phase 1/2 study.
Intellia plans to initiate the global pivotal Phase 3 study, including U.S. patients, as early as the third quarter of 2024, subject to regulatory feedback.
In June, Intellia announced additional positive interim results from the Phase 1 portion of the ongoing Phase 1/2 study of NTLA-2002. Across all 10 patients, a 95% mean reduction in monthly attack rate was observed after a single dose of NTLA-2002 through the latest follow-up. The median duration of follow-up was 9.0 months (range of 5.6 – 14.1 months). At all three dose levels evaluated, NTLA-2002 has been well tolerated, and the majority of adverse events were mild in severity. These interim data were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2023, held in Hamburg, Germany, and virtually.
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 a Clinical Trial Application (CTA) by year-end 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 became chair of the audit committee on June 15, 2023. In June, Intellia announced the retirement of Jean-François Formela, M.D., from its board of directors, effective June 15, 2023.
Upcoming Events

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

Wells Fargo Healthcare Conference, September 6, Everett, Massachusetts
BMO Gene Editing Event, September 26, virtual
Cantor Global Healthcare Conference, September 27, New York City
Upcoming Milestones

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

NTLA-2001 for ATTR amyloidosis:
Submit an IND application in September 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 by year-end 2023.
Initiate a global pivotal study for NTLA-2001 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:
Complete enrollment in the Phase 2 portion of the Phase 1/2 study in 2H 2023.
AATD Franchise:
Submit a CTA application for NTLA-3001 for AATD-associated lung disease by year-end 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.
Second Quarter 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.1 billion as of June 30, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of approximately $227.3 million. The decrease was offset in part by $24.6 million of interest income, $8.0 million of reimbursement from its collaborators, $1.5 million of net equity proceeds from the Company’s "At the Market" (ATM) program and $3.3 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue decreased by $0.4 million to $13.6 million during the second quarter of 2023, compared to $14.0 million during the second quarter of 2022.
R&D Expenses: Research and development expenses increased by approximately $25.1 million to $115.3 million during the second quarter of 2023, compared to $90.2 million during the second quarter of 2022. This increase was primarily driven by the advancement of our lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $22.4 million for the second quarter of 2023.
G&A Expenses: General and administrative expenses increased by $8.5 million to $30.7 million during the second quarter of 2023, compared to $22.1 million during the second quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $5.1 million. Stock-based compensation expense included in general and administrative expenses was $14.0 million for the second quarter of 2023.
Net Loss: The Company’s net loss was $123.7 million for the second quarter of 2023, compared to $100.7 million during the second quarter of 2022.
Conference Call to Discuss Second Quarter 2023 Results

The Company will discuss these results on a conference call today, Thursday, August 3 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 August 3 at 12 p.m. ET.