On May 2, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the first quarter of 2024 and provided a business update (Press release, Regeneron, MAY 2, 2024, View Source [SID1234642596]).

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"The Regeneron team has already made substantial progress this year, delivering our approved medicines to more patients around the globe, advancing our pipeline consisting of dozens of clinical-stage programs, and relentlessly pursuing cutting-edge science," said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. "We had a strong quarter of EYLEA HD uptake, and we are well positioned to continue our leadership in retinal diseases. Dupixent continues to grow at a remarkable pace seven years into its launch and is currently treating over 850,000 patients across a variety of diseases characterized by type 2 inflammation. Our promising oncology franchise is strengthening, driven by strong global growth in Libtayo sales and potential regulatory approvals later this year for linvoseltamab in relapsed/refractory multiple myeloma."

Financial Highlights

($ in millions, except per share data) Q1 2024 Q1 2023 % Change
Total revenues $ 3,145 $ 3,162 (1% )
Total revenues excluding Ronapreve(a)(b) $ 3,145 $ 2,940 7%
GAAP net income $ 722 $ 818 (12% )
GAAP net income per share – diluted $ 6.27 $ 7.17 (13% )
Non-GAAP net income(a) $ 1,116 $ 1,168 (4% )
Non-GAAP net income per share – diluted(a) $ 9.55 $ 10.09 (5% )

"We are off to a strong start in 2024 as reflected in our solid first quarter financial results and the progress we have made across our growing pipeline," said Christopher Fenimore, Senior Vice President, Finance and Chief Financial Officer of Regeneron. "While investing in innovation remains our top capital allocation priority, the recent authorization by Regeneron’s board of directors of a new $3.0 billion share repurchase program provides us with additional flexibility to continue returning capital to shareholders over time."

Business Highlights

Key Pipeline Progress
Regeneron has over 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

EYLEA HD (aflibercept) 8 mg

In January 2024, the European Commission (EC) and Japan’s Ministry of Health, Labour and Welfare (MHLW) each approved EYLEA 8 mg (known as EYLEA HD in the United States) for the treatment of patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME).
In January 2024, the United States Centers for Medicare & Medicaid Services (CMS) assigned a permanent and product-specific J-code (J0177) for EYLEA HD, which became effective on April 1, 2024. J-codes simplify and streamline the billing and reimbursement processes for Medicare Part B treatments, allowing for efficient claims processing.
Dupixent (dupilumab)

The U.S. Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent as an add-on maintenance treatment in adult patients with uncontrolled chronic obstructive pulmonary disease (COPD) and evidence of type 2 inflammation. A regulatory application is also under review in the European Union (EU) and Japan.
A Phase 3 study for Dupixent in asthma for children aged 2 to 5 years was initiated.
In February 2024, the MHLW in Japan approved Dupixent for the treatment of chronic spontaneous urticaria (CSU) in adults and children aged 12 years and older whose disease is not adequately controlled with existing therapy. A regulatory application has also been submitted in the EU.
Oncology Programs

The FDA accepted the BLA seeking accelerated approval for linvoseltamab, a bispecific antibody targeting BCMA and CD3, to treat adult patients with relapsed/refractory (R/R) multiple myeloma that has progressed after at least three prior therapies, and the BLA was granted priority review with a target action date of August 22, 2024. A Phase 3 confirmatory trial is currently enrolling patients. A regulatory application is also under review in the EU.
In April 2024, the Company presented positive pivotal data from the Phase 1/2 trial of linvoseltamab in patients with R/R multiple myeloma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024. The linvoseltamab data reinforced previously shared findings and included a 71% objective response rate (ORR), with 46% of patients achieving a complete response (CR) or better.
In March 2024, the FDA issued Complete Response Letters (CRLs) for the BLA for odronextamab, a bispecific antibody targeting CD20 and CD3, in R/R follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL). The only approvability issue cited in the CRLs is related to the enrollment status of the confirmatory trials. The CRLs (one for R/R FL and one for R/R DLBCL) did not identify any approvability issues with the clinical efficacy or safety, trial design, labeling, or manufacturing. A regulatory application for R/R DLBCL and R/R FL remains under review in the EU.
In 2023, the Company initiated a Phase 2/3 study of the combination of fianlimab, an antibody to LAG-3, and Libtayo (cemiplimab) in first-line metastatic melanoma. This study is enrolling faster than expected and will be conducted solely as a Phase 3 study with the final analysis to be reported during 2025.
Other Programs

The FDA has extended the approval of Praluent (alirocumab) as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C) lowering therapies to include pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).
A Phase 2 study for itepekimab, an antibody to IL-33, for non-cystic fibrosis bronchiectasis (NCFB) was initiated.
A Phase 2 study for ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP), was initiated by the Company’s collaborator Alnylam Pharmaceuticals, Inc. in patients with cerebral amyloid angiopathy (CAA).
Corporate and Business Development Updates

In April 2024, the Company acquired full development and commercialization rights to 2seventy bio, Inc.’s oncology and autoimmune preclinical and clinical stage cell therapy pipeline. Under the terms of the agreement, the Company made a $5 million up-front payment, and has assumed ongoing program, infrastructure, and personnel costs related to the product candidates acquired. In addition, the Company is obligated to pay 2seventy bio a regulatory milestone upon the first major market approval of the first approved product; and, with respect to any approved product, a low single-digit percent royalty on sales.
In April 2024, the Company and Mammoth Biosciences, Inc. entered into a collaboration agreement to research, develop, and commercialize in vivo CRISPR-based gene editing therapies for multiple tissues and cell types. Under the terms of the agreement, the Company purchased an aggregate of $95 million of Mammoth preferred stock and is obligated to make a $5 million up-front payment. The parties will jointly select and research collaboration targets, and then Regeneron will lead development and commercialization.
In April 2024, the Company’s board of directors authorized a new share repurchase program to repurchase up to an additional $3.0 billion of the Company’s common stock. Repurchases may be made from time to time at management’s discretion through a variety of methods. The program has no time limit and can be discontinued at any time.
First Quarter 2024 Financial Results
Revenues

($ in millions) Q1 2024 Q1 2023 % Change
Net product sales:
EYLEA HD – U.S. $ 200 $ — *

EYLEA – U.S. 1,202 1,434 (16% )
Total EYLEA HD and EYLEA – U.S. 1,402 1,434 (2% )
Libtayo – Global 264 177 49%
Praluent – U.S. 70 40 75%
Evkeeza – U.S. 24 15 60%
Inmazeb – Global 1 2 *
Total net product sales 1,761 1,668 6%

Collaboration revenue:
Sanofi 910 798 14%
Bayer 356 357 —%
Other 1 223 (100% )
Other revenue 117 116 1%
Total revenues $ 3,145 $ 3,162 (1% )

* Percentage not meaningful

Net product sales of EYLEA in the U.S. decreased in the first quarter of 2024, compared to the first quarter of 2023, primarily due to changing market dynamics, resulting in lower volumes and a lower net selling price. In addition, aggregate net product sales of EYLEA and EYLEA HD in the first quarter of 2024 were negatively impacted by approximately $40 million due to a sequential net reduction in wholesaler inventory.

Sanofi collaboration revenue increased in the first quarter of 2024, compared to the first quarter of 2023, primarily due to the Company’s share of profits from commercialization of antibodies, which were $804 million in the first quarter of 2024, compared to $637 million in the first quarter of 2023. The change in the Company’s share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales.

The decrease in other collaboration revenue in the first quarter of 2024, compared to the first quarter of 2023, was due to lower sales of Ronapreve. Under the Company’s Roche collaboration agreement, the Company records collaboration revenue in connection with payments from Roche attributable to gross profits from sales of Ronapreve; however, the Company does not expect any additional Roche collaboration revenue from Ronapreve in future periods.

Refer to Table 4 for a summary of collaboration revenue.

Operating Expenses

GAAP %
Change
Non-GAAP(a) %
Change
($ in millions) Q1 2024 Q1 2023 Q1 2024 Q1 2023
Research and development (R&D) $ 1,248 $ 1,101 13% $ 1,122 $ 960 17%
Acquired in-process research and development (IPR&D) $ 7 $ 56 (88% ) * * n/a
Selling, general, and administrative (SG&A) $ 689 $ 601 15% $ 584 $ 515 13%
Cost of goods sold (COGS) $ 240 $ 208 15% $ 196 $ 168 17%
Cost of collaboration and contract manufacturing (COCM) $ 193 $ 249 (22% ) * * n/a
Other operating expense (income), net $ 15 $ (1 ) ** $ — * **

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded.
** Percentage not meaningful
GAAP and non-GAAP R&D expenses increased in the first quarter of 2024, compared to the first quarter of 2023, driven by the advancement of the Company’s late-stage oncology programs, and higher headcount and headcount-related costs.
Acquired IPR&D for first quarter of 2023 included a $45 million up-front payment in connection with the Company’s collaboration agreement with Sonoma Biotherapeutics, Inc.
GAAP and non-GAAP SG&A expenses increased in the first quarter of 2024, compared to the first quarter of 2023, due to higher commercialization-related expenses to support the Company’s launch of EYLEA HD and higher headcount and headcount-related costs primarily related to the international expansion in support of Libtayo and hematology product launch preparations.
GAAP and non-GAAP COGS increased in the first quarter of 2024, compared to the first quarter of 2023, primarily due to higher start-up costs for the Company’s Rensselaer, New York fill/finish facility.
COCM decreased in the first quarter of 2024, compared to the first quarter of 2023, primarily due to lower Dupixent manufacturing costs as a result of the transition to a higher-yielding manufacturing process.
GAAP other operating expense (income), net, for the first quarter of 2024 reflects a charge related to the increase in the estimated fair value of the contingent consideration liability recognized in connection with the Company’s 2023 acquisition of Decibel Therapeutics, Inc.

On May 2, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported financial results for the first quarter ended March 31, 2024 (Press release, Puma Biotechnology, MAY 2, 2024, View Source [SID1234642595]). Unless otherwise stated, all comparisons are for the first quarter 2024 compared to the first quarter 2023.

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Product revenue, net consists entirely of revenue from sales of NERLYNX, Puma’s first commercial product. Product revenue, net in the first quarter of 2024 was $40.3 million, compared to product revenue, net of $46.8 million in the first quarter of 2023.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss of $4.8 million, or $0.10 per basic and diluted share, for the first quarter of 2024, compared to net income of $1.4 million, or $0.03 per basic and diluted share, for the first quarter of 2023.

Non-GAAP adjusted net loss was $2.4 million, or $0.05 per basic and diluted share, for the first quarter of 2024, compared to non-GAAP adjusted net income of $4.2 million, or $0.09 per basic and diluted share, for the first quarter of 2023. Non-GAAP adjusted net (loss) income excludes stock-based compensation expense. For a reconciliation of GAAP net (loss) income to non-GAAP adjusted net (loss) income and GAAP net (loss) income per share to non-GAAP adjusted net (loss) income per share, please see the financial tables at the end of this news release.

Net cash provided by operating activities for the first quarter of 2024 was $11.3 million, compared to $2.6 million in the first quarter of 2023. At March 31, 2024, Puma had cash, cash equivalents and marketable securities of $107.2 million, compared to cash, cash equivalents and marketable securities of $96.0 million at December 31, 2023.

"In February, we were pleased to initiate ALISertib in CAncer (ALISCA-Lung1), a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "We also look forward to presenting updated data from the clinical trial of alisertib in combination with osimertinib in patients with metastatic EGFR-mutant non-small cell lung cancer who have developed osimertinib resistance, as well as results from the biomarker studies of the randomized trial of alisertib plus fulvestrant versus alisertib alone in hormone receptor-positive, HER2-negative breast cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. We remain committed to our goal to clinically develop alisertib, while carefully managing our resources to achieve positive net income for this year."

Mr. Auerbach added, "We anticipate the following key milestones over the next 12 months: (i) presentation of biomarker studies from the randomized trial of alisertib plus fulvestrant versus alisertib alone in hormone receptor-positive, HER2-negative breast cancer (Q2 2024); (ii) updated data from the clinical trial of alisertib in combination with osimertinib in patients with metastatic EGFR-mutant non-small cell lung cancer who have developed osimertinib resistance (Q2 2024); (iii) initiation of ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (Q4 2024); and (iv) interim data from ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (Q4 2024)."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, Puma’s first commercial product, license revenue from Puma’s sub-licensees and royalty revenue. For the first quarter ended March 31, 2024, total revenue was $43.8 million, of which $40.3 million was net product revenue and $3.5 million was royalty revenue. This compares to total revenue of $52.8 million in the first quarter of 2023, of which $46.8 million was net product revenue and $6.0 million was royalty revenue.

Operating Costs and Expenses

Total operating costs and expenses were $46.1 million for the first quarter of 2024, compared to $48.4 million for the first quarter of 2023.

Cost of Sales

Cost of sales was $10.7 million for the first quarter of 2024, compared to $13.2 million for the first quarter of 2023. The $2.5 million decrease resulted primarily from lower royalty expense reflecting decreased worldwide net sales.

Selling, General and Administrative Expenses

Selling, general and administrative expenses were $21.8 million for the first quarter of 2024, compared to $22.5 million for the first quarter of 2023. The $0.7 million decrease resulted primarily from payroll-related expenses and stock-based compensation, partially offset by an increase in professional fees and expenses.

Research and Development Expenses

Research and development expenses were $13.6 million for the first quarter of 2024, compared to $12.7 million for the first quarter of 2023. The $0.9 million increase resulted primarily from an increase in clinical trial expense of approximately $1.0 million, due to a milestone payment associated with a neratinib clinical trial, partially offset by a decrease in neratinib-related consultant and contractors expense.

Total Other Income (Expenses)

Total other expenses were $2.3 million for the first quarter of 2024, compared to total other expenses of $2.8 million for the first quarter of 2023. The $0.5 million decrease resulted primarily from an increase in interest income, which resulted from higher interest rates and increased cash investments.

Second Quarter and Full Year 2024 Financial Outlook

Second Quarter 2024

Full Year 2024

Net Product Revenue

$43 -45 million

$183 – $190 million

Royalty Revenue

$2.5 – $3 million

$30 – $33 million

License Revenue

$0 million

$1 – $2 million

Net Income/(Loss)

$(6) – $(9) million

$12 – $15 million

Gross to Net Adjustment

22% – 23%

21.5% – 22.5%

Conference Call

Puma Biotechnology will host a conference call to report its first quarter 2024 financial results and provide an update on the Company’s business and outlook at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, May 2, 2024. The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days.

On May 2, 2024 Pulse Biosciences, Inc. (Nasdaq: PLSE) ("Pulse" or the "Company"), a company leveraging its novel and proprietary CellFX Nanosecond Pulsed Field Ablation (nsPFA) technology, reported that the Company’s Board of Directors has set the record date for the Company’s previously announced rights offering (the "Rights Offering"), which will be available to all holders of record of the Company’s common stock, par value $0.001 per share (the "Common Stock"), as of the close of the market on Thursday, May 16, 2024 (the "Record Date") (Press release, Pulse Biosciences, MAY 2, 2024, View Source [SID1234642594]).

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The Company intends to distribute to all holders of Common Stock as of the Record Date non-transferable subscription rights to purchase up to an aggregate of 6,000,000 units ("Units") at a price per Unit equal to the lesser of: (i) $10 (the "Initial Price") and (ii) the volume weighted average price of the Common Stock for the ten trading day period through and including the expiration date of the Rights Offering, currently contemplated to be Thursday, June 13, 2024 (the "Alternate Price"). Only persons who own Company stock on the May 16, 2024 Record Date will be able to participate in the Rights Offering. Assuming that the Rights Offering is fully subscribed, the Company will receive gross proceeds of $60,000,000, less expenses related to the Rights Offering. As indicated below, please refer to the Registration Statement on Form S-3, as amended, for more complete information regarding the planned Rights Offering.

Each stockholder will receive one subscription right entitling the holder to purchase a fraction of a Unit for each share of Common Stock owned at 5:00 p.m., Eastern Time, on the Record Date. Each Unit shall consist of one share of Common Stock and two warrants, each being a warrant to purchase one-half of one share of Common Stock at an exercise price per whole share that shall be equal to 110% of the per-Unit subscription price (provided, that, the aggregate number of shares of Common Stock that shall be issuable upon the exercise of each set of warrants included in a given subscription for Units shall be rounded up to the nearest whole share). Each warrant will be exercisable immediately upon completion of the Rights Offering and will expire on the fifth anniversary of the completion of the Rights Offering. The respective warrants will be subject to redemption by the Company for $0.01 per underlying share of Common Stock, on not less than thirty (30) days’ written notice, if the volume weighted average price of our Common Stock equals or exceeds: (i) in respect of one such warrant, 150% of the exercise price for the warrants, subject to adjustment, per whole share, for twenty (20) consecutive trading days, and (ii) in respect of the other such warrant, 200% of the exercise price for the warrants, subject to adjustment, per whole share, for twenty (20) consecutive trading days, provided that, in each case, the Company may not redeem the warrants prior to the date that is three months after the issuance date. To the extent that the Alternate Price is lower than the Initial Price, the Company will sell additional Units, but will not sell fractional Units.

The Rights Offering will include an over-subscription right to permit each rights holder that exercises its basic subscription rights in full to purchase additional Units that remain unsubscribed at the expiration of the offering, but the Company will not sell fractional Units. The availability of this over-subscription right will be subject to certain terms and conditions to be set forth in the offering documents.

Pulse has filed a registration statement (including a prospectus) on Form S-3 with the U.S. Securities and Exchange Commission (the "SEC") on April 3, 2024, as amended on each of April 15, 2024, April 23, 2024, April 25, 2024, and April 30, 2024 (the "Registration Statement"), which has not yet become effective. The Registration Statement covers, among other things, the Rights Offering to which this communication relates. The Units, and the securities comprising such Units, may not be sold, nor may offers to buy be accepted, prior to the time the Registration Statement becomes effective. Before you invest, you should read the final prospectus in the Registration Statement, together with any prospectus supplement, that we will file prior to commencing any Rights Offering, and the documents incorporated by reference in the prospectus (or any prospectus supplement), as well as the other documents Pulse has filed with the SEC for more complete information about Pulse and the Rights Offering. You may get these documents for free by visiting EDGAR on the SEC’s website at www.sec.gov.

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On May 2, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the first quarter ended March 31, 2024 and provided a business update (Press release, Protara Therapeutics, MAY 2, 2024, View Source [SID1234642593]).

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"We have made significant progress thus far in 2024, and with cash resources expected to fund operations into 2026, we are well positioned to execute our programs in oncology and rare disease," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We are pleased with the positive three-month data announced last month from our clinical program in patients with non-muscle invasive bladder cancer (NMIBC), which support the potential for TARA-002 to play a meaningful role in the treatment landscape. Looking ahead, we are on track to present interim data from our ADVANCED-2 trial of TARA-002 in patients with NMIBC in the second half of this year."

Mr. Shefferman continued, "We also recently aligned with the U.S. Food and Drug Administration (FDA) on a path forward for intravenous (IV) Choline Chloride in patients dependent on parenteral nutrition (PN). We continued to enroll pediatric patients in our Phase 2 STARBORN-1 trial of TARA-002 in lymphatic malformations (LMs), an underserved population with no FDA-approved therapies."

Recent Progress and Highlights

Corporate Update

In April 2024, Protara closed a $45.0 million private placement. The offering was led by RA Capital Management and Acorn Bioventures and included participation from new and existing investors such as Boxer Capital, Woodline Partners LP, Catalio Capital Management, StemPoint Capital, Armistice Capital, Velan Capital and a healthcare fund.
TARA-002 in NMIBC

In April 2024, the Company announced positive data from three-month evaluable carcinoma in situ (CIS) patients treated across its ongoing clinical program of TARA-002 in high-risk NMIBC, including Bacillus Calmette-Guérin (BCG)-unresponsive, BCG-experienced and BCG-naïve patient populations. The overall three-month complete response (CR) rate prior to reinduction for 16 evaluable patients treated across three trials with varying BCG status was 38%, with a CR rate of 63% in CIS-only patients and 13% in patients with CIS +Ta/T1. A 43% CR rate was observed in BCG-Unresponsive/Experienced patients. TARA-002 demonstrated a favorable safety and tolerability profile, with no Grade 3 or greater treatment-related adverse events.
The Company expects to share preliminary results from a pre-planned risk-benefit analysis of the ongoing Phase 2 open-label ADVANCED-2 trial in the second half of 2024. The Phase 2 open-label ADVANCED-2 trial is assessing intravesical TARA-002 in NMIBC patients with CIS (± Ta/T1) who are BCG-Unresponsive (n=75-100) and BCG-Naïve (n=27). The BCG-Unresponsive cohort has been designed to be registrational aligned with the FDA’s 2018 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry. Trial subjects will receive an induction course of six weekly intravesical instillations, and following mandatory biopsy at three months, will either receive a reinduction course of six weekly intravesical instillations of TARA-002, or the first maintenance course of three weekly installations every three months for an additional 12 months.
In addition to the ADVANCED-2 trial, the Company intends to assess higher dosing at an 80KE1 dose and systemic priming prior to initiation of intravesical administration, as well as the combination of TARA-002 with a checkpoint inhibitor in NMIBC patients with CIS.
IV Choline Chloride for Patients on PN

In April 2024, the Company announced alignment with the FDA on a registrational path forward for IV Choline Chloride in patients dependent on PN. Previously, the Company had been pursuing an indication in intestinal failure-associated liver disease (IFALD) and following feedback from the FDA, is pursuing a broader indication in patients on PN who are or may become unable to synthesize choline from oral or enteral nutrition sources. The Company expects to advance the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PN.
TARA-002 in LMs

Dosing continues to progress in STARBORN-1, a Phase 2 clinical trial of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs. Including an age de-escalation safety lead-in, the trial will enroll approximately 30 patients who will receive up to four injections of TARA-002 spaced approximately six weeks apart. The primary endpoint of the trial is the proportion of participants with macrocystic and mixed cystic LMs who demonstrate clinical success, defined as having either a CR (90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as measured by axial imaging.
First Quarter 2024 Financial Results

As of March 31, 2024, cash, cash equivalents and investments in marketable debt securities totaled $55.2 million. The Company expects its cash, cash equivalents, and investments in marketable debt securities, together with approximately $42.0 million in net proceeds from its April 2024 private placement, will be sufficient to fund its planned operations and data milestones into 2026.
Research and development expenses for the first quarter of 2024 increased to $7.7 million from $5.1 million for the prior year period. The increases were primarily due to an increase in expenses related to clinical trial and non-clinical activities for TARA-002 of $1.8 million as well as an increase of $1.1 million in personnel-related expenses, partially offset by a reduction in clinical development activities for Choline of $0.3 million.
General and administrative expenses for the first quarter of 2024 decreased to $4.1 million from $4.6 million for the prior year period. This decrease was primarily due to a reduction of $0.5 million in personnel-related expenses, inclusive of $0.3 million of stock-based compensation.
For the first quarter of 2024, Protara incurred a net loss of $11.1 million, or $0.97 per share, compared with a net loss of $9.0 million, or $0.80 per share, for the same period in 2023. Net loss for the first quarter of 2024 included approximately $1.2 million of stock-based compensation expenses.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and natural killer cells. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations (LMs)

LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of three years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride

IV Choline Chloride is an investigational, intravenous phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition. Choline is a known important substrate for phospholipids that are critical for healthy liver function and also plays an important role in modulating gene expression, cell membrane signaling, brain development and neurotransmission, muscle function, and bone health. PN patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PN formulations containing choline. Approximately 80 percent of PN-dependent patients are choline-deficient and have some degree of liver damage, which can lead to hepatic failure. There are currently no available PN formulations containing choline. In the U.S. alone, there are approximately 40,000 patients on long-term parenteral nutrition who would benefit from an IV formulation of choline. IV Choline Chloride has the potential to become the first FDA approved IV choline formulation for PN patients. IV Choline Chloride has been granted Orphan Drug Designation by the FDA for the prevention of choline deficiency in PN patients. The Company was issued a U.S. patent claiming a choline composition with a term expiring in 2041.

On May 2, 2024 Novartis reported that it has entered into an agreement to acquire Mariana Oncology, a preclinical-stage biotechnology company based in Watertown, Massachusetts focused on developing novel radioligand therapies (RLTs) to treat cancers with high unmet patient need (Press release, Novartis, MAY 2, 2024, View Source [SID1234642592]).

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The transaction bolsters the Novartis RLT pipeline and expands the company’s research infrastructure and clinical supply capabilities, supporting Novartis strategic priorities in oncology and RLT platform innovation.
The acquisition encompasses a robust portfolio of RLT programs spanning lead optimization to early development across a range of solid tumor indications such as breast, prostate and lung cancer – including development candidate MC-339, an actinium-based RLT being investigated in small cell lung cancer.

"The acquisition of Mariana Oncology reflects our commitment to radioligand therapy as one of our company’s key technology platforms and strengthens our leadership in this field," said Fiona Marshall, President of Biomedical Research at Novartis. "We are excited to work with the Mariana team to bring forward next-generation RLTs for patients living with cancer and together shape the future of RLT as a pillar for oncology treatment."

RLTs, or radiopharmaceuticals, are a form of precision medicine that combines a tumor-targeting molecule (ligand) with a therapeutic radioisotope (a radioactive particle). RLTs bind to specific receptors expressed on the surface of certain types of tumors. Once bound to a target cell, emissions from the therapeutic radioisotope cause DNA damage that can inhibit cell growth and replication and potentially trigger cell death. This targeted approach enables the delivery of radiation to the tumor, while limiting damage to the surrounding cells.

"As pioneers in radioligand therapies, we are dedicated to building on our scientific leadership and expanding the breadth of these potentially transformative treatments to a broader range of cancer types," said Shiva Malek, Global Head of Oncology for Biomedical Research at Novartis. "This acquisition brings to Novartis phenomenal talent and new capabilities in RLT research that complement our wide-ranging internal efforts to explore novel isotopes, combinations, disease areas, and more."

As of today, Novartis has two approved RLTs for certain patients with metastatic castration-resistant prostate cancer and for certain types of gastroenteropancreatic neuroendocrine tumors. The company’s early and late pipeline has several programs in or entering the clinic, including a spectrum of studies and assets for prostate cancer, as well as other preclinical and discovery programs to identify the next wave of novel RLTs. Novartis is actively exploring new isotopes and new combinations with complementary mechanisms of action, as well as looking at new disease areas for RLT.

Under the terms of the agreement, Novartis will make an upfront payment of USD 1 billion and additional USD 750 million in payments upon completion of pre-specified milestones.

The transaction is subject to customary closing conditions.