Protara Therapeutics Announces First Quarter 2023 Financial Results and Business Update

On May 4, 2023 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, 2023 and provided a business update (Press release, Protara Therapeutics, MAY 4, 2023, View Source [SID1234631047]).

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"We are off to a strong start in 2023, notably with the recent presentation of positive preliminary data from the dose escalation portion of the ADVANCED-1 trial of TARA-002 in patients with high-grade non-muscle invasive bladder cancer (NMIBC) and expect to sustain this productive momentum in the months ahead," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Supported by these exciting preliminary findings, we are keenly focused on continued execution across the NMIBC program, including the recently announced Phase 1b/2 ADVANCED-2 trial of TARA-002 in patients with high-grade carcinoma in situ (CIS), which we expect to commence in the second half of this year. With final regulatory clearance from the U.S. Food and Drug Administration (FDA) on our Phase 2 trial in lymphatic malformations (LMs), we look forward to initiating STARBORN-1 in the near future and progressing our program to bring a much-needed therapy to these pediatric patients who have no approved treatments today. We remain committed to unlocking the full potential of TARA-002 and look forward to sharing our progress throughout the coming quarters."

Recent Highlights

TARA-002 in NMIBC

In April 2023 at the American Urological Association Annual Meeting, the Company announced positive preliminary results from the Phase 1a dose-escalation component of the ADVANCED-1 clinical trial of TARA-002, its investigational cell-based therapy, for the treatment of patients with high-grade NMIBC. The clinical data indicate that TARA-002 was generally well tolerated and anti-tumor activity was observed, including tumor regression in all three evaluable patients with CIS, including one heavily pre-treated Bacillus Calmette-Guérin (BCG)-unresponsive patient who achieved a complete response.

The Company plans to initiate ADVANCED-2, a Phase 1b/2 open-label trial evaluating intravesical TARA-002 in up to 102 patients with high-grade CIS. The Phase 1b trial is expected to enroll 27 patients with CIS (± Ta/T1), BCG-Naïve or BCG-experienced, who have not received intravesical BCG for at least 24 months prior to CIS diagnosis. The Phase 2 trial is expected to enroll 75 patients with BCG-unresponsive CIS (± Ta/T1). ADVANCED-2 is expected to initiate in the second half of 2023.
TARA-002 in Lymphatic Malformations (LMs)

In April 2023, the Company received regulatory clearance from the FDA to commence STARBORN-1, a Phase 2 clinical trial of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs. Trial start-up activities are well underway in the ten pediatric centers of excellence participating in the trial, and initiation is expected in the fourth quarter of 2023.
IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD)

Protara’s prospective study to enhance understanding of the incidence of IFALD in patients dependent on parenteral nutrition is ongoing, with results expected in the third quarter of 2023. The Company continues to engage with the FDA and plans to use both regulatory feedback and results from the prospective study to inform next steps for the IV Choline Chloride development program.
First Quarter 2023 Financial Results

As of March 31, 2023, cash, cash equivalents and restricted cash were $89.5 million. The Company expects its current cash and cash equivalents will be sufficient to fund its planned operations into 2025.
Research and development (R&D) expenses for the first quarter of 2023 decreased to $5.1 million from $5.3 million during the first quarter of 2022.
General and administrative expenses for the first quarter of 2023 decreased to $4.6 million from $5.6 million for the prior year period. This decrease was primarily due to decreases of $0.5 million in employee related expenses (including $0.3 million of stock-based compensation expense), $0.3 million resulting from a reduction in directors and officers liability insurance premiums, as well as $0.2 million related to a reduction in market development activities.
For the first quarter of 2023, Protara reported a net loss of $9.0 million, or $0.80 per share, compared with a net loss of $10.8 million, or $0.96 per share, for the same period in 2022. Net loss for the first quarter of 2023 included approximately $1.6 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 strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha are secreted by immune cells to induce a strong inflammatory reaction and destroy the abnormal cells.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th 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 3 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 and Intestinal Failure-associated Liver Disease (IFALD)

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.

8-K – Current report

On May 4, 2023 Protalix BioTherapeutics, Inc. (NYSE American:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the first quarter ended March 31, 2023 and provided a business update on recent regulatory, clinical and corporate developments (Press release, Protalix, MAY 4, 2023, View Source [SID1234631046]).

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"While we are awaiting for the European Commission and the U.S. Food and Drug Administration decisions, we and our partner, Chiesi, remain committed to bringing PRX-102 to market and improving the lives of patients with Fabry disease," said Dror Bashan, Protalix’s President and Chief Executive Officer. "In addition, we are making progress in our early stage PRX-115 program in severe gout with the initiation of our first-in-human Phase I clinical trial."

2023 First Quarter and Recent Business Highlights

Regulatory Advancements

● On February 24, 2023, the Company, together with its development and commercialization partner for PRX-102, Chiesi Global Rare Diseases (Chiesi), announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine Agency (EMA) had adopted a positive opinion, recommending marketing authorization for PRX-102 (pegunigalsidase alfa) for adult patients with Fabry disease. The positive opinion was based on a marketing authorization application (MAA) submitted to the EMA on February 7, 2022. The MAA included final data from the Company’s phase III BRIDGE and BRIGHT clinical trials; 12-month interim data from the Company’s phase III BALANCE clinical trial; and final data from the Company’s phase I/II clinical trial from naïve/untreated patients, including the related extension study, using 1 mg/kg every two weeks dosing. Data from the 24-month final analysis of the phase III BALANCE clinical trial was submitted to the EMA during the review period. The CHMP opinion was referred for final action to the European Commission.
Clinical Developments

● On March 27, 2023, the Company announced that the first patient was dosed in a First in Human (FIH) phase I clinical trial of PRX-115, the Company’s recombinant PEGylated uricase product candidate under development as a potential treatment for severe gout. The FIH trial is a double-blind, placebo-controlled, single ascending dose study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of PRX-115 in approximately 56 patients with elevated uric acid levels (>6.0 mg/dL) and no previous exposure to PEGylated uricase. The study is being conducted at New Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines.
Corporate Developments

● On March 22, 2023, the Company’s request for a voluntary delisting of the Company’s common stock from the Tel Aviv Stock Exchange ("TASE") took effect. The last trading day on the TASE was March 20, 2023.
First Quarter 2023 Financial Highlights

● The Company recorded revenues from selling goods of $5.1 million during the three months ended March 31, 2023, a decrease of $3.9 million, or 43%, compared to revenues of $9.0 million for the three months ended March 31, 2022. The decrease resulted primarily from a decrease of $2.7 million in sales to Brazil and a decrease of $1.1 million in sales to Pfizer, both resulting from timing differences.
● The Company recorded revenues from license and R&D services of $4.5 million for the three months ended March 31, 2023, a decrease of $2.6 million, or 37%, compared to revenues of $7.1 million for the three months ended March 31, 2022. Revenues from license and R&D services are comprised primarily of revenues the Company recognized in connection with the Chiesi Agreements.
● Cost of goods sold was $3.1 million for the three months ended March 31, 2023, a decrease of $2.9 million, or 48%, from cost of goods sold of $6.0 million for the three months ended March 31, 2022. The decrease in cost of goods sold was primarily the result of the decrease in sales of goods.
● For the three months ended March 31, 2023, the Company’s total research and development expenses were approximately $5.8 million comprised of approximately $3.5 million in subcontractor-related expenses, approximately $1.5 million of salary and related expenses, approximately $0.1 million of materials-related expenses and approximately $0.7 million of other expenses. For the three months ended March 31, 2022, the Company’s total research and development expenses were approximately $8.8 million comprised of approximately $5.8 million in subcontractor-related expenses, approximately $2.0 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.8 million of other expenses. Total decrease in research and developments expenses was $3.0 million, or 34%, for the three months ended March 31, 2023 compared to the three months ended March 31, 2022. The decrease in research and development expenses primarily resulted from the completion of the Company’s Fabry clinical program and of a substantial portion of the regulatory processes related to the Biologics License Application resubmission (BLA) and MAA submission for PRX-102.
● Selling, general and administrative expenses were $3.1 million for the three months ended March 31, 2023, a decrease of $0.1 million, or 3%, compared to $3.2 million for the three months ended March 31, 2022. A decrease of approximately $0.4 million in salary and related expenses was partially offset by an increase of $0.3 million in professional fees.
● Financial expenses, net were $0.5 million for the three months ended March 31, 2023, compared to financial expenses, net of $0.4 million for the three months ended March 31, 2022.
● In the three months ended March 31, 2023, the Company recorded income taxes of approximately $0.2 million. Income taxes were recorded as Section 174 of the U.S. Tax Cuts and Jobs Act of 2017 went into effect on January 1, 2022.
● Cash and cash equivalents were approximately $33.0 million at March 31, 2023.
● Net loss for the three months ended March 31, 2023 was approximately $3.1 million, or $0.05 per share, basic and diluted, compared to a net loss of $2.3 million, or $0.05 per share, basic and diluted, for the same period in 2022.
Conference Call and Webcast Information

The Company will host a conference call today, May 4, 2023 at 8:30 am EDT, to review the regulatory, clinical and corporate developments, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call:

Conference Call Details:

Date:Thursday, May 4, 2023

Time:8:30 a.m. Eastern Daylight Time (EDT)

Toll Free (U.S.):1-800-954-0653

International:1-212-231-2918

Conference ID:22026736

Webcast Details:

The conference will be webcast live from the Company’s website and will be available via the following links:

Company Link: View Source

Webcast Link: Registration – View Source

Conference ID: 22026736

Please access the websites at least 15 minutes ahead of the conference call to register, download and install any necessary audio software.

The conference call will be available for replay for two weeks on the Events Calendar of the Investors section of the Company’s website, at the above link.

PharmaMar launches clinical trial on solid tumors with its new molecule PM54

On May 4, 2023 PharmaMar (MSE:PHM) reported the recruitment of the first patient in a new Phase I clinical trial for the treatment of patients with different types of solid tumors with its new molecule of marine origin: PM54 (Press release, PharmaMar, MAY 4, 2023, View Source [SID1234631045]).

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This is the first-in-human (FIH) clinical trial with this new compound that is being carried out in hospitals in Spain, other European countries and the United States. This clinical trial aims to find the recommended dose of the treatment.

This new molecule has been tested in the laboratory, both in cell cultures, in vitro, and in vivo. In both cases, PharmaMar’s new compound showed promising anti-tumor activity in a wide variety of tumor types. PM54 is the second PharmaMar compound to enter into the clinical development stage in the last few months after PM534, which FIH phase I trial was initiated in December 2022.

Orna Therapeutics to Present Progress of Lead Program ORN-101 at PEGS and ASGCT

On May 4, 2023 Orna Therapeutics, a biotechnology company pioneering a new investigational class of engineered circular RNA (oRNA) therapies, reported two presentations at the Protein Engineering Summit (PEGS) taking place May 15-19 in Boston as well as a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting in Los Angeles May 16-20 (Press release, OrnaTherapeutics, MAY 4, 2023, View Source [SID1234631043]). Orna is presenting preclinical results for ORN-101, an in situ CAR program in development, as well as further details about its platform.

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"We are paving the way for advancements in RNA therapeutics that reach beyond infectious disease to treat cancer and genetic disorders," said Robert Mabry, PhD, Chief Scientific Officer at Orna. "Our ORN-101 program demonstrates the benefits of our platform’s ability to create a paradigm-changing treatment with the characteristics we believe matter most to patients, including a rapid timeline from diagnosis to treatment, strong expression and tumor-killing potency at low dose, and a regimen without the harsh chemotherapeutic lymphodepletion protocols typically required for standard engineered cell therapies."

Details for the presentations are as follows:

PEGS presentations

Title: Synthetic Circular RNA as a New Therapeutic Modality

Speaker & Chair: Nelson Chau, PhD, Senior Vice President, Platform

Session: Innovating RNA Therapeutics

Time: Tuesday May 16, 4:30pm ET

Title: In situ CAR Therapy Using oRNA

Speaker: Amy Becker, PhD, Director of Immunology

Session: Cellular Reprogramming, Increasing Specificity

Time: Thursday, May 18, 1:50pm ET

ASGCT poster

Title: In situ CAR Therapy Using oRNA Lipid Nanoparticles Regress Tumors in vivo

Speaker: Akinola Emmanuel, PhD, Principal Scientist

Board: 1119

Time: Thursday, May 18, 12-2pm PT

About ORN-101:

ORN-101, Orna’s lead program, is an in situ CAR therapy designed to modify a patient’s immune cells inside their body. Comprising an oRNA molecule packaged inside a proprietary lipid nanoparticls (LNP) formulation, this easily redosable format could avoid patient lymphodepletion and allow for reliable dose control, overcoming barriers of existing ex vivo CAR-T therapies without sacrificing efficacy. Preclinical data demonstrates tumor suppression and eradication in an animal model, suggesting the possibility that oRNA-LNP based cancer therapies could eventually overtake cell therapies.

Oncternal Therapeutics Provides Business Update and Announces First Quarter 2023 Financial Results

On May 4, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported a business update and announced first quarter 2023 financial results (Press release, Oncternal Therapeutics, MAY 4, 2023, View Source [SID1234631042]).

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"Oncternal is intensely focused on advancing our cell therapy and androgen receptor (AR) inhibitor programs to reach significant clinical inflection points over the coming months. We are excited about the potential of ONCT-808, our ROR1-targeting CAR T, as it builds on the extensive clinical experience with zilovertamab, as well as with zilovertamab vedotin, an antibody drug conjugate, which has shown that ROR1 can be targeted without unwanted off-tumor, on-target activity. We are also enthusiastic about our novel and first-in-class dual-action AR inhibitor, ONCT-534, which demonstrated in preclinical studies that its unique mechanism of action may address significant unmet needs related to AR-resistance mechanisms in patients with metastatic castrate-resistant prostate cancer (mCRPC). We expect to initiate a Phase 1/2 study of ONCT-534 shortly after an IND submission in mid-2023, and to report initial clinical data in the first half of 2024, well within our expected cash runway period," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "Our decision to pause clinical development of zilovertamab with ibrutinib was a necessary step due to a major shift in the Bruton’s tyrosine kinase (BTK) inhibitor landscape, along with the announced plans by Abbvie to withdraw ibrutinib’s FDA accelerated approval in MCL. While we continue to actively explore options to develop zilovertamab through partnerships and collaborations, this decision allowed us to extend our expected cash runway into 2025 and support key clinical catalysts for our cell therapy and prostate cancer programs."

Recent Highlights

In January 2023, we obtained our first Institutional Review Board (IRB) approval for the Phase 1/2 study of ONCT-808 of our autologous ROR1 targeting CAR T for patients with aggressive B cell lymphoma (NCT05588440)
In March 2023, we concluded Investigational New Drug (IND)-enabling studies for ONCT-534, our novel dual-action androgen receptor inhibitor (DAARI) to support a Phase 1/2 clinical trial in patients with mCRPC who are resistant to androgen receptor (AR) inhibitor drugs such as enzalutamide and abiraterone
In April 2023, we announced that the Phase 3 and the Phase 1/2 studies of zilovertamab in combination with ibrutinib will be closed, based on the rapidly changing commercial landscape for BTK inhibitors
Expected Upcoming Milestones

ONCT-808, our autologous ROR1-targeted CAR T cell therapy
Initial clinical data available by the end of 2023
Additional clinical readouts in 2024
ONCT-534, our dual-action androgen receptor inhibitor
U.S. IND application submission in mid-2023
Phase 1/2 clinical study initiation in the second half of 2023
Initial clinical data available in the first half of 2024

First Quarter 2023 Financial Results

Our grant revenue was $0.2 million for the first quarter ended March 31, 2023. Our total operating expenses for the first quarter ended March 31, 2023 were $12.3 million, including $1.9 million in non-cash stock-based compensation expense. Research and development expenses for the quarter totaled $9.0 million, and general and administrative expenses for the quarter totaled $3.3 million. Net loss for the first quarter was $11.5 million, or a loss of $0.20 per share, basic and diluted. As of March 31, 2023, we had approximately 58.7 million shares of common stock outstanding, $54.3 million in cash, cash equivalents and short-term investments and no debt. We believe these funds will be sufficient to fund our operations into 2025.