On March 14, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided an overview of recent developments (Press release, UroGen Pharma, MAR 14, 2024, View Source [SID1234641173]).

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"In 2023, UroGen achieved important operational and clinical milestones, setting us up for further success in the coming years," said Liz Barrett, President and Chief Executive Officer of UroGen. "The Phase 3 ATLAS and ENVISION trials both produced meaningful and unprecedented results underscoring the potential of UGN-102 to fundamentally change the way patients with low-grade intermediate-risk non-muscle invasive bladder cancer are treated. We look forward to reporting the 12-month duration of response data from ENVISION in the second quarter of 2024 and to completing submission of an NDA in September of this year. UGN-102 has the potential to address a more than $3 billion market opportunity and, if approved, has the potential to be transformative for our company. JELMYTO continues to show double digit growth with patient and physician adoption expected to continue to increase."

2023 and Recent Business Highlights:

UGN-102 (mitomycin) for intravesical solution:

In January 2024, UroGen initiated submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The first part of the submission was the Chemistry, Manufacturing and Controls (CMC) sections. The FDA indicated that evaluation of duration of complete response at 12-months from the pivotal ENVISION trial will be sufficient to support submission of the NDA. The company plans to complete the submission in September 2024 with a potential FDA decision as early as the first quarter of 2025.
Positive top-line data from ATLAS Phase 3 clinical trial highlighting UGN-102 as non-surgical treatment option for LG-IR-NMIBC published in The Journal of Urology.
JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC):

Generated annual net product revenue of $82.7 million in 2023, compared with $64.4 million in 2022 in representing ~28% annual growth.
Patient enrollment forms, new patient starts, and total doses each grew approximately 25% year-over-year. First-time writers, activated sites and repeat accounts also continue to grow.
A retrospective study investigated whether patients with higher-volume low-grade disease could achieve disease-free status using partial ablation or biopsy before JELMYTO treatment during initial ureteroscopy. The study found no significant difference in disease-free rates between complete ablation (78.6%), partial ablation (57.6%), or biopsy-only (66.7%) groups during initial ureteroscopy. Tumor size prior to JELMYTO induction also showed no significant impact on disease-free rates. The study aimed to find alternatives to nephroureterectomy for preserving kidney function and to assess JELMYTO’s efficacy in managing larger volume disease. Findings from the study were published online in Urologic Oncology: Seminars and Original Investigations online.
Next-generation novel mitomycin-based formulation for urothelial cancers

In January 2024, UroGen announced a license and supply agreement with medac GmbH to develop a next-generation novel mitomycin-based formulation for urothelial cancers. UGN-103 and UGN-104 combine UroGen’s RTGel technology with medac’s licensed mitomycin formulation. The agreement and development program potentially allow UroGen to extend the patent protection on its urothelial cancer franchise. medac has intellectual property protection for its mitomycin formulation expected to last until June 2035 and UroGen has pending U.S. patent applications which may provide protection until December 2041.
UroGen plans to initiate Phase 3 studies to explore the safety and efficacy of UGN-103 and UGN-104 in LG-IR-NMIBC and LG-UTUC, respectively, in 2024.
Up to $100 Million Letter of Credit Facility with Funds Managed by Pharmakon

Announced signing of a restructured loan agreement with Pharmakon Advisors providing UroGen additional funding of up to $100 million. Under the terms of the restructured agreement, the interest rate on the previously funded $100 million loan is reduced, and the initiation of the payback period will be delayed following UGN-102 approval. The restructured agreement also includes a credit facility of up to $100 million. As part of the agreement, UroGen is required to draw down on the first tranche of $25 million of the credit facility by September 30, 2024, and will have the option to access as much as an additional $75 million following UGN-102 approval.
Fourth Quarter and Full Year 2023 Financial Results

JELMYTO Revenue: UroGen reported JELMYTO net product revenues of $23.5 million in the fourth quarter of 2023, compared to $18.1 million for the same period in 2022. Net JELMYTO product revenue for the full year 2023 was $82.7 million, compared to $64.4 million in 2022. Despite strong unit growth, full year 2023 net revenues were impacted by higher than forecast 340B chargebacks and first time estimated Medicare refunds for discarded drug, offset by non-patient purchases.

R&D Expense: Research and development expenses for the fourth quarter of 2023 were $11.3 million, including non-cash share-based compensation expense of $0.5 million as compared to $14.5 million, including non-cash share-based compensation expense of $0.6 million, for the same period in 2022. Research and development expenses for the full year 2023 were $45.6 million, including non-cash share-based compensation expense of $1.9 million as compared to $52.9 million, including non-cash share-based compensation expense of $2.6 million, in 2022.

SG&A Expense: Selling, general and administrative expenses for the fourth quarter of 2023 were $24.6 million, including non-cash share-based compensation expense of $2.1 million. This compares to $21.6 million, including non-cash share-based compensation expense of $1.8 million, for the same period in 2022. Selling, general and administrative expenses for the full year 2023 were $93.3 million, including non-cash share-based compensation expense of $7.4 million. This compares to $82.8 million, including non-cash share-based compensation expense of $8.0 million, in 2022.

Financing on Prepaid Forward Obligation: UroGen reported non-cash financing expense related to the prepaid forward obligation to RTW Investments of $5.5 million in the fourth quarter of 2023, compared to $5.1 million in the same period in 2022. Non-cash financing expense related to the RTW Investments obligation was $21.6 million for the full year 2023, compared to $21.6 million in 2022. The rate applied to cash payments incurred in 2023 is 13% based on global JELMYTO net product sales of $82.7 million in 2023.

Interest Expense on Long-Term Debt: Interest expense related to the $100 million term loan facility with funds managed by Pharmakon Advisors was $3.6 million and $14.7 million, respectively for the fourth quarter and full year 2023, compared to $3.2 million and $8.4 million in the same periods in 2022. The higher amount in 2023 was a result of interest expense for four full quarters in 2023, whereas the first and second tranches of the loan were funded in March 2022 and December 2022, respectively.

Net Loss: UroGen reported a net loss of $26.0 million or ($0.72) per basic and diluted share in the fourth quarter of 2023 compared with a net loss of $28.9 million or ($1.25) per basic and diluted share in the same period in 2022. Net loss was $102.2 million or ($3.55) per basic and diluted share in the full year 2023 compared with a net loss of $109.8 million or ($4.81) per basic and diluted share in 2022.

Cash & Cash Equivalents: As of December 31, 2023, cash, cash equivalents and marketable securities totaled $141.5 million.

2024 Revenue, Operating Expense and RTW Expense Guidance: The Company anticipates full year 2024 net product revenues from JELMYTO to be in the range of $95 to $102 million. Increased discounts related to Medicare refunds for discarded drugs and 340B purchases will further impact net revenues in 2024. The Company also expects full year 2024 operating expenses in the range of $175 to $185 million, including non-cash share-based compensation expense of $6 to $11 million, subject to market conditions. The Company also reiterates anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW Investments in the range of $21 to $26 million. Of this amount approximately $12.4 to $13.3 million is expected to be in cash.

Conference Call & Webcast Information: Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review UroGen’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast.

UROGEN PHARMA LTD.

SELECTED CONSOLIDATED BALANCE SHEETS

(U.S. dollars in thousands)

(Unaudited)

December 31,
2023

December 31,
2022

Cash and cash equivalents and marketable securities

$

141,469

$

99,963

Total assets

$

178,311

$

135,619

Total liabilities

$

243,523

$

224,980

Total shareholders’ deficit

$

(65,212

)

$

(89,361

)

UROGEN PHARMA LTD.

CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

(U.S. dollars in thousands, except share and per share data)

(Unaudited)

Three months ended
December 31,
(Unaudited)

Year ended

December 31,

2023

2022

2023

2022

Revenue1

$

23,530

$

18,092

$

82,713

$

64,357

Cost of revenue

2,286

2,263

9,361

7,654

Gross profit

21,244

15,829

73,352

56,703

Operating expenses:

Research and development expenses

11,302

14,477

45,614

52,906

Selling, general and administrative expenses

24,551

21,634

93,274

82,838

Total operating expenses

35,853

36,111

138,888

135,744

Operating loss

(14,609

)

(20,282

)

(65,536

)

(79,041

)

Financing on prepaid forward obligation

(5,505

)

(5,081

)

(21,552

)

(21,559

)

Interest expense on long-term debt

(3,586

)

(3,223

)

(14,715

)

(8,438

)

Interest and other income, net

1,538

406

3,479

1,010

Loss before income taxes

$

(22,162

)

$

(28,180

)

$

(98,324

)

$

(108,028

)

Income tax expense

(3,854

)

(689

)

(3,920

)

(1,775

)

Net loss

$

(26,016

)

$

(28,869

)

$

(102,244

)

$

(109,783

)

Net loss per ordinary share basic and diluted

$

(0.72

)

$

(1.25

)

$

(3.55

)

$

(4.81

)

Weighted average shares outstanding, basic and diluted

36,153,634

23,088,891

28,834,303

22,806,812

1.

2023 full-year JELMYTO net revenues include gross-to-net unfavorability driven by higher 340B chargebacks and estimated Medicare refunds for discarded drugs, offset by $4.4 million in CREATES Act sales, of which $2.4 million was realized in Q4 2023.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with LG-UTUC. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.
are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of low-grade, intermediate-risk, non-muscle invasive bladder cancer (LG-IR-NMIBC). Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its NDA submission for UGN-102 in September with a potential FDA decision as early as the first quarter of 2025.

On March 14, 2024 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, reported financial results for the fourth quarter and full year ended December 31, 2023 and provided corporate updates (Press release, Terns Pharmaceuticals, MAR 14, 2024, View Source [SID1234641172]).

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"I joined Terns last month at a pivotal stage in the company’s growth as we advance towards initial data readouts from our Phase 1 clinical programs for TERN-601, our oral small molecule GLP-1 agonist for obesity, and TERN-701, our allosteric BCR-ABL inhibitor for CML. Importantly, our global Phase 1 trial of TERN-701 allows for the enrollment of second line CML patients, which makes the study attractive for participants given that there is no allosteric inhibitor currently approved for 2L CML patients," said Amy Burroughs, chief executive officer of Terns. "Terns made meaningful progress throughout 2023, as highlighted by the initiation of these two clinical programs, the positive Phase 2 data readout from our potentially best in class THR-β and the advances in discovery for our small-molecule GIPR modulators for obesity."

Recent Pipeline Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML)

•
Global Phase 1 CARDINAL trial initiated in fourth quarter 2023 and is progressing
o
CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK) and efficacy of TERN-701 in patients with previously treated CML
o
The study design leverages insights from the ongoing Phase 1 trial in China, which support a starting dose that appears safe and clinically active based on emerging early clinical data
•
The CARDINAL trial design provides multiple opportunities to potentially differentiate TERN-701 in the CML treatment landscape
o
Opportunity to efficiently develop TERN-701 as a dose-optimized allosteric inhibitor for CML
o
Inclusion of second-line (2L) chronic phase CML patients, which better positions Terns to potentially move directly into a 2L (or earlier line) pivotal study
o
Reduced competition for trial enrollment as no allosteric inhibitor is currently approved for 2L CML patients
•
Interim data from initial CARDINAL dose escalation cohorts expected in the second half of 2024
•
In March 2024, the United States Food and Drug Administration (FDA) granted Orphan Drug Designation for TERN-701 for the treatment of chronic myeloid leukemia
•
Terns plans to host a virtual KOL event in mid-2024 to focus on the interpretation of early CML datasets

TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

•
Phase 1 clinical trial of Terns’ lead oral GLP-1 receptor agonist in healthy obese or overweight participants is ongoing
o
Primary endpoints include safety and tolerability assessments
o
Secondary and exploratory endpoints include PK and change in body weight over 28 days
•
Top-line data, including 28-day body weight loss, expected in the second half of 2024
•
Terns continues preclinical efforts to identify promising oral, small-molecule combination candidates for obesity (e.g., GLP-1 + THR-β, GLP-1 + GIPR agonist / antagonist)

TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist

•
Terns continues to evaluate opportunities for TERN-501 in metabolic diseases
o
Based on non-clinical studies, THR-β is an orthogonal mechanism to GLP-1, potentially providing broader metabolic and liver benefits in addition to increased weight loss
o
Non-clinical data suggests that TERN-501 may augment the weight loss effects of a GLP-1 receptor agonist, as demonstrated in a diet-induced obese mouse model
•
Terns has decided to limit spend in MASH given the current regulatory and clinical development requirements for the indication

TERN-800 Series: Oral, small-molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators

•
Discovery efforts are ongoing for the TERN-800 series of small molecule GIPR modulators for obesity
•
GIPR modulators (agonists and antagonists) have the potential for combination with GLP-1 receptor agonists, such as TERN-601

Corporate Updates

•
In February 2024, Terns announced the appointment of Amy Burroughs as chief executive officer and board member of Terns

Fourth Quarter and Full Year 2023 Financial Results

Cash Position: As of December 31, 2023, cash, cash equivalents and marketable securities were $263.4 million, as compared with $283.1 million as of December 31, 2022. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2026.

Research and Development (R&D) Expenses: R&D expenses were $17.5 million and $63.5 million for the quarter and year ended December 31, 2023, respectively, as compared with $10.7 million and $39.6 million for the quarter and year ended December 31, 2022, respectively.

General and Administrative (G&A) Expenses: G&A expenses were $6.6 million and $39.1 million for the quarter and year ended December 31, 2023, respectively, as compared with $6.2 million and $22.4 million for the quarter and year ended December 31, 2022, respectively.

Net Loss: Net loss was $21.0 million and $90.2 million for the quarter and year ended December 31, 2023, respectively, as compared with $15.8 million and $60.3 million for the quarter and year ended December 31, 2022, respectively.

On March 14, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported preclinical proof of concept data for its conditionally-activated tri-specific antibody platform (Press release, Purple Biotech, MAR 14, 2024, View Source [SID1234641171]).

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"Our tribody platform is differentiated with its dual engagers including its NK cell engager having a dual mechanism of action, in addition to the conditionally activated T cell engager. We are excited about the potential of this platform to produce a pipeline of promising drug candidates that can be effective across numerous solid cancer tumors," stated Gil Efron, Chief Executive Officer of Purple Biotech.

Prof. Amir Horowitz, Assistant Professor of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, commented, "Purple Biotech’s tribody platform, apart from being a NK cell engager, via the anti-NKG2A arm, also functions as an important immune checkpoint inhibitor of both NK cells and specific subsets of T cells, unleashing both innate and adaptive immune systems against the tumor. This conditionally-activated platform requires a complex model for optimal and translational analysis, hence patient-derived explant (PDE) models were selected to demonstrate the added value of the anti-NKG2A modality."

Using 5T4-expressing lung cancer PDE model, where the immune cells and the tumor cells are derived from the same patient (autologous model), the studies showed a synergistic effect of the T cell engager and NK cell engager arms. While each bispecific agent, 5T4xCD3 or 5T4xNKG2A, showed only low response, the tribody platform’s leading candidate IM1240 (5T4xCD3xNKG2A) having both engagers in one product, demonstrated a synergistic strong anti-tumor response. This effect is activated through the presence of 5T4 positive tumor cells. The advantage of the 5T4 arm was also validated using in-vitro PBMC-mediated cytotoxicity of cancer cell line studies which demonstrated 5T4-specific effect. While cytotoxicity at pM range was observed in 5T4-positive lung and breast cancer cells, no effect was observed against 5T4-negative cancer cells.

Purple Biotech’s cleavable capping technology confines the compound’s therapeutic activity to the local tumor micro environment (TME), which increases the anticipated therapeutic window in patients. This cap is attached to the anti-CD3 moiety and blocks its interaction with circulating CD3 positive T cells, thereby impeding potential off-tumor adverse reactions and also improving PK properties. The cap is designed to be cleaved off by multiple TME-specific proteases, which increase the likelihood for cleavage by many tumor types. Upon removal of this cap, the anti-CD3 moiety of the molecule is freed to bind and activate T lymphocytes against the tumor via CD3.

On March 14, 2024 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 fiscal year ended December 31, 2023, and provided a business update (Press release, Protalix, MAR 14, 2024, View Source [SID1234641170]).

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"2023 was a significant year for Protalix, as we received regulatory approvals of Elfabrio for the treatment of adult patients with Fabry disease and advanced our growing pipeline," said Dror Bashan, Protalix’s President and Chief Executive Officer. "As the second drug produced through our proven protein expression platform, Elfabrio’s approval is a welcome milestone for Fabry disease patients and their families. Our commercial partner Chiesi Global Rare Diseases is continuing to position Elfabrio for global success, with launches underway in the United States, the European Union, the UK and additional markets where approvals were granted. As we continue to provide Chiesi with operational support for its activities, we have turned our attention to developing a rich pipeline of innovative assets. For example, PRX-115, our proprietary recombinant PEGylated uricase for the treatment of severe gout, is currently being studied in a first-in-human phase I clinical trial. We anticipate that results from the trial will be published in the second quarter of 2024. As a company powered by a professional team and solid financials, and with the potential for revenue growth, we are poised for an exciting future and look forward to making a positive impact on patients’ lives and delivering long-term value to our stockholders."

Fiscal Year 2023 and Recent Business Highlights

Regulatory and Commercial Advancements

The Company, together with its development and commercialization partner, Chiesi Global Rare Diseases (Chiesi), a business unit of the Chiesi Group, gained marketing authorizations in the United States, the European Union, the UK, Switzerland and Israel for Elfabrio (pegunigalsidase alfa), a PEGylated recombinant human α-Galactosidase-A enzyme, for the treatment of adult patients with confirmed Fabry disease. Elfabrio is administered via intravenous infusion at a dose of 1 mg/kg every two weeks.

● On May 5, 2023, the Company announced that the European Commission (EC) granted marketing authorization to Elfabrio in the European Union for the treatment of adult patients with Fabry disease.
● On May 10, 2023, the Company announced that the U.S. Food and Drug Administration (FDA) approved Elfabrio in the United States for the treatment of adult patients with Fabry disease.
● On August 15, 2023, Chiesi announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Elfabrio in Great Britain for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.
● On September 11, 2023, Swissmedic, the national authorization and supervisory authority for drugs and medical products in Switzerland, announced the approval of Elfabrio in Switzerland for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.
● In January 2024, the Israeli Ministry of Health granted principle approval of Elfabrio for adult patients with a confirmed diagnosis of Fabry disease.
The FDA approval triggered a $20.0 million milestone payment from Chiesi. In addition, the Company generated $17.5 million from sales of Elfabrio to Chiesi during 2023 post-regulatory approval, as Chiesi is building its inventory and recruiting commercial patients in the United States and Europe.

Clinical Developments

In March 2023, the first patient was dosed in the Company’s First in Human (FIH) Phase I clinical trial of PRX–115, a 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, which is fully-enrolled, is being conducted at the 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. The Company anticipates that preliminary results from the study will be published in the second quarter of 2024.

Corporate Developments

On September 14, 2023, Eliot Richard Forster, Ph.D. began his tenure as Chairman of the Board of Directors, replacing former Chairman Zeev Bronfeld, who retired for personal reasons.

Fiscal Year 2023 Financial Highlights

● The Company recorded revenues from selling goods of $40.4 million for the year ended December 31, 2023, an increase of $15.1 million, or 60%, compared to revenues of $25.3 million for the year ended December 31, 2022. The increase resulted primarily from an increase of $14.1 million in sales of Elfabrio drug product to Chiesi, following the approvals by the FDA and the European Medicines Agency (EMA) of Elfabrio, an increase of $0.1 million in sales to Pfizer Inc., or Pfizer, and of $0.9 million in sales to Brazil, resulting from timing differences.

● The Company recorded revenues from license and R&D services of $25.1 million for the year ended December 31, 2023, an increase of $2.8 million, or 13%, compared to revenues of $22.3 million for the year ended December 31, 2022. The increase resulted from the $20.0 million regulatory milestone payment from Chiesi in connection with the FDA approval of Elfabrio which was partially offset by a decrease of $17.2 million in revenues recognized in connection with the R&D performance obligation under the Chiesi Agreements as the Company has completed the phase III clinical program thereunder. Revenues from license and R&D services represent primarily the revenues the Company recognized for services provided under the Chiesi Agreements.
● Cost of goods sold was $23.0 million for the year ended December 31, 2023, an increase of $3.4 million, or 17%, compared to cost of goods sold of $19.6 million for the year ended December 31, 2022. The increase in cost of goods sold was primarily the result of the increase in sales of goods to Chiesi, Brazil and to Pfizer. Sales to Chiesi included certain drug substance costs which had already been recognized as research and development expenses as it was produced as part of research and development activities. Accordingly, the related cost of goods sold does not include the costs of such drug substance.
● For the year ended December 31, 2023, the Company’s total research and development expenses were approximately $17.1 million, comprised of approximately $6.3 million in subcontractor-related expenses, approximately $7.8 million of salary and related expenses, approximately $0.6 million of materials-related expenses and approximately $2.4 million of other expenses. For the year ended December 31, 2022, the Company’s total research and development expenses were approximately $29.3 million, comprised of approximately $17.8 million in subcontractor-related expenses, approximately $7.3 million of salary and related expenses, approximately $1.4 million of materials-related expenses and approximately $2.8 million of other expenses. Total decrease in research and developments expenses was $12.2 million, or 42%, for the year ended December 31, 2023 compared to the year ended December 31, 2022. The decrease in research and development expenses resulted primarily from a $11.5 million decrease in subcontractor-related expenses in connection with the PRX-102 clinical trials, and a $0.8 million decrease in materials-related expenses.
● Selling, general and administrative expenses were $15.0 million for the year ended December 31, 2023, an increase of $3.3 million, or 28%, from $11.7 million for the year ended December 31, 2022. The increase resulted primarily from an increase of approximately $2.3 million in one-time cash bonuses, share-based compensation and salary and salary-related expenses, as well as an increase of $0.3 million in travel, conferences and employee training expenses.
● Financial expense, net was $1.9 million for the year ended December 31, 2023, an increase of $0.5 million, or 36%, compared to financial expenses of $1.4 million for the year ended December 31, 2022. The increase was primarily due to a decrease of $0.9 million in income related to exchange rates as well as an increase in interest expenses of $0.7 million which was partially offset by a gain recognized due to conversions of a portion of the 2024 Notes of $0.4 million and a $0.6 million increase in interest income.
● For the year ended December 31, 2023, the Company recorded income taxes of approximately $0.3 million, a decrease of $0.2 million, or 40%, compared to tax expenses of $0.5 million for the year ended December 31, 2022. The income taxes resulted primarily from the provision for current taxes on income mainly derived from U.S. taxable global intangible low-taxed income (GILTI) mainly in respect of Section 174 of the U.S. Tax Cuts and Jobs Act (the "TCJA"). Effective in 2022, Section 174 of the TCJA requires all U.S. companies, for tax purposes, to capitalize and subsequently amortize R&D expenses that fall within the scope of Section 174 over five years for research activities conducted in the United States and over 15 years for research activities conducted outside of the United States rather than deducting such costs in the current year. The net income taxes gives effect to a valuation allowance release equal to approximately $3.1 million.
● Cash, cash equivalents and short-term bank deposits were approximately $44.6 million at December 31, 2023.
● Net income for the year ended December 31, 2023 was approximately $8.3 million, or $0.12 per share, basic, and $0.09 per share, diluted, compared to a net loss of $14.9 million, or $0.31 per share, basic and diluted, for the same period in 2022.
Conference Call and Webcast Information

The Company will host a conference call today, March 14, 2024 at 8:30 am EDT, to review the financial results and provide a business update. To participate in the conference call, please dial the following numbers prior to the start of the call:

On March 14, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the full year and fourth quarter ended December 31, 2023 (Press release, Monte Rosa Therapeutics, MAR 14, 2024, View Source [SID1234641169]).

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"We made excellent pipeline and corporate progress during 2023 and early 2024, highlighted by the encouraging initial clinical results reported from our MRT-2359 Phase 1/2 study in October. We also continued to advance our VAV1-directed MGD, MRT-6160, for autoimmune diseases toward the clinic, and we progressed MRT-8102, a NEK7-directed MGD targeting IL-1b and the NLRP3 inflammasome, into IND-enabling studies. We are excited about the broad potential of MRT-2359 in MYC-driven cancers, as well as the opportunity that exists with both the VAV1 and NEK7 programs to address pathways of emerging clinical significance in systemic and neurological autoimmune and inflammatory diseases," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "In addition, we entered into a strategic research collaboration with Roche to enable broader application of our technology. All combined, the terrific progress we made in the last 12 month highlights the uniqueness and differentiation of our approach and the strength of our ML/AI-driven QuEEN discovery engine. We look forward to building on that success with continued pipeline execution across multiple programs targeting substantial patient populations, and our anticipated cash runway into the first half of 2026 positions us well to do so."

2023 AND RECENT HIGHLIGHTS

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In October 2023, Monte Rosa announced interim clinical data from the Phase 1 dose escalation part of the ongoing Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors demonstrating tumor size reductions in heavily pretreated patients with biomarker-positive cancers and favorable pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles. Enrollment is ongoing in backfill cohorts at clinically active doses using a 5-days-on-drug, 9-days-off-drug schedule and in dose escalation cohorts using a 21-days-on, 7-days-off-drug schedule. The Company anticipates determining the recommended Phase 2 dose in Q2 2024, reporting updated Phase 1 study results thereafter, and initiating the Phase 2 portion of the study before year-end.
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In December 2023, Monte Rosa received U.S. Food & Drug Administration (FDA) Fast Track Designation for MRT-2359 for the treatment of patients with previously treated, metastatic small cell lung cancer (SCLC) with L-MYC or N-MYC expression. MRT-2359 previously received Fast Track designation from the FDA for the treatment of patients with previously treated, metastatic NSCLC with L-MYC or N-MYC expression.
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MRT-6160, a VAV1-targeting MGD designed to treat multiple systemic and neurological immunological and inflammatory diseases, is on track towards an anticipated Investigational New Drug (IND) application filing with the FDA in Q2 2024, and a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study initiation in healthy volunteers in midyear 2024. The Company recently completed preclinical GLP toxicology studies in rats and non-human primates, demonstrating a highly favorable profile with no significant changes in peripheral immunophenotyping assessments.
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Monte Rosa recently announced the nomination of MRT-8102 as the first development candidate for its NEK7 program, targeting diseases driven by IL-1b and the NLRP3 inflammasome. MRT-8102 is an orally bioavailable MGD that has shown potent, selective, and durable degradation of NEK7 and near-complete reduction of IL-1b in a non-human primate model following ex vivo stimulation of whole blood. IND-enabling studies are ongoing, and an IND submission is anticipated in Q1 2025. The Company is also advancing other differentiated NEK7-directed MGDs.
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In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with global healthcare leader Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa Therapeutics received an upfront payment of $50 million and is eligible to receive future preclinical, clinical, commercial, and sales milestone payments that could exceed $2 billion, as well as tiered royalties. Roche has the option to expand the collaboration with an additional set of targets. If exercised, Monte Rosa would be eligible for an additional upfront payment of up to $28 million and potential preclinical, clinical, commercial, and sales milestones exceeding $1 billion, as well as tiered royalties.
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Edmund Dunn was recently promoted to Principal Accounting Officer. Edmund has more than 25 years of experience as a finance professional and has been with Monte Rosa since March of 2021. Andrew Funderburk was recently appointed as Senior Vice President, Head of Investor Relations and Strategic Finance. He was previously Managing Director at Kendall Investor Relations, LLC, and Managing Director and Partner at the healthcare and life sciences consulting firm Health Advances.

ANTICIPATED UPCOMING MILESTONES

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Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024 and report updated Phase 1 clinical results thereafter. Initiate the Phase 2 portion of the study before year-end. The Company is exploring Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors such as hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including NSCLC, SCLC, and solid tumors with amplifications of L- and N-MYC.
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Submit an IND application for MRT-6160 in Q2 2024 and initiate a Phase 1 SAD/MAD study in healthy volunteers in mid-2024. Monte Rosa expects to subsequently initiate proof-of-concept studies in autoimmune diseases spanning gastroenterology, dermatology, rheumatology, and neurology indications.

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Submit an IND application for MRT-8102 in Q1 2025.
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Nominate a development candidate for the CDK2 preclinical program in 2024.

UPCOMING PRESENTATIONS

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Monte Rosa plans to present a poster at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that treatment with MRT-2359 resulted in marked tumor regressions in an AR-V7-expressing 22RV1 xenograft mouse model of c-MYC-driven prostate cancer associated with resistance to anti-androgen agents. The Company also plans to present at an educational session at AACR (Free AACR Whitepaper) on molecular glue degraders.

FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL RESULTS

Research and Development (R&D) Expenses: R&D expenses for the fourth quarter of 2023 were $27.1 million, compared to $24.9 million for the fourth quarter of 2022, and $111.3 million for the year ended December 31, 2023, compared to $85.1 million for the year ended December 31, 2022. These increases were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine, and reflect increased personnel expense and external R&D costs including laboratory-related expenses to achieve these milestones. Non-cash stock-based compensation constituted $2.2 million of R&D expenses for Q4 2023, compared to $1.8 million in the same period in 2022, and $8.9 million and $5.6 million for the years ended December 31, 2023 and 2022, respectively.

General and Administrative (G&A) Expenses: G&A expenses for the fourth quarter of 2023 were $7.7 million compared to $7.6 million for the fourth quarter of 2022, and $32.0 million for the year ended December 31, 2023, compared to $27.3 million for the year ended December 31, 2022. The increase in G&A expenses was a result of increased headcount and expenses in support of the Company’s growth and operations. G&A expenses included non-cash stock-based compensation of $1.8 million for the fourth quarter of 2023, compared to $1.6 million for the same period in 2022, and $7.7 million and $6.1 million for the years ended December 31, 2023 and 2022, respectively.

Net Loss: Net loss for the fourth quarter of 2023 was $33.3 million, compared to $30.8 million for the fourth quarter of 2022, and $135.4 million for the year ended December 31, 2023, compared to $108.5 million for the year ended December 31, 2022.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of December 31, 2023, were $237.0 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $183.0 million as of September 30, 2023. The increase of $54 million was primarily related to the proceeds from the Roche collaboration and registered direct offering in Q4 2023.

The Company expects its cash and cash equivalents, including proceeds from the Roche collaboration, to be sufficient to fund planned operations and capital expenditures into the first half of 2026.

About MRT-2359

MRT-2359 is a potent, highly selective and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and dermatological disorders. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.

About MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1b and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1b release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1b and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 potently, selectively, and durably degrades NEK7 and results in near-complete reductions of IL-1b models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.