On November 14, 2023 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported a business update and announced financial results for the quarter ended September 30, 2023 (Press release, VBI Vaccines, NOV 14, 2023, View Source [SID1234637643]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In Q3, we were focused on pipeline execution with continued revenue growth for PreHevbrio, meaningful data readouts and clinical advancements of our lead development candidates, and the announcement of a next-generation proprietary technology that blends the benefits of our eVLP technology with those of mRNA platforms," said Jeff Baxter, VBI’s President and CEO. "Additionally, in this period of challenging financial markets for biotechnology companies, we are intensely focused on managing our operating expenses and capital to fuel sustainable growth and value for key stakeholders."

Recent Key Program Achievements and Projected Upcoming Milestones

Hepatitis B (HBV)

PreHevbrio [Hepatitis B Vaccine (Recombinant)]

Global net product sales increased 52% from Q2 2023 with $1.1 million earned in Q3 2023
Net product sales are net of the provision for discounts, chargebacks, rebates, and fees – in the aggregate, these discounts reduced sales by $0.6 million in Q3 2023, from $1.7 million gross sales to $1.1 million net sales
Quarter-over-quarter momentum continues to grow, with more than a 10% increase in total customer base in Q3 as compared to Q2 2023
Contracting network across multiple market segments also continues to see growth, including with retail partners, Integrated Delivery Networks (IDNs) and large hospital systems, multiple large military and federal facilities, prisons, and independent and public health clinics
July 2023: Exclusive licensing deal with Brii Biosciences (Brii Bio) announced for the development and commercialization of PreHevbri in the Asia Pacific region, excluding Japan
October 2023: Peer-reviewed publication of review of data from studies of PreHevbrio published in Expert Review of Vaccines
Manuscript title: "PreHevbrio: the first approved 3-antigen hepatitis B vaccine"
Q4 2023: New market launches expected in additional European Union countries through partnership with Valneva (under brand name PreHevbri)
VBI-2601 (BRII-179): HBV Immunotherapeutic Candidate

July 2023: Announced exclusive global licensing agreement with Brii Bio for the development and commercialization of VBI-2601
This expanded partnership adds VBI-2601 to Brii Bio’s HBV portfolio, which, through a series of strategic investments and partnerships is among the most advanced in the chronic HBV field
VBI will continue to share in the success of VBI-2601, with the potential to receive regulatory and commercial milestone payments, in addition to potential double-digit royalties on global sales of VBI-2601
September 2023: Brii Bio announced topline interim results of Phase 2 study evaluating VBI-2601 in combination with pegylated interferon-alpha (PEG-IFNα) in chronic HBV patients
The combination treatment elicited improved hepatitis B S-antigen (HBsAg) loss and seroconversion vs. PEG-IFNα alone both at the end of treatment and after 12 weeks of follow up
November 2023: In two late-breaking poster presentations at AASLD The Liver Meeting 2023, Brii Bio announced new data from Phase 2 studies of VBI-2601 (BRII-179) highlighting progress towards achieving HBV functional cure:
Direct evidence that BRII-179-induced functional antibody responses can contribute to increased and sustained HBsAg loss rate
New insight utilizing BRII-179 to enrich patients with intrinsic humoral immune responses for higher HBsAg loss or HBV functional cure rates
Glioblastoma (GBM)

VBI-1901: Cancer Vaccine Immunotherapeutic Candidate

September 2023: Announcement of first patients dosed in the randomized, controlled Phase 2b study of VBI-1901, an FDA Fast Track and Orphan Drug Designated cancer vaccine candidate, in recurrent GBM patients
Around Year-End 2023: Expected initiation of VBI-1901 study arm, as part of Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a Phase 2 adaptive platform trial, in combination with Agenus Inc.’s anti-PD-1, balstilimab, in primary GBM patients
H2 2024: Interim data analyses from Phase 2b study in recurrent GBM patients expected, subject to speed of patient enrollment
COVID-19 & Coronaviruses

VBI-2901: Multivalent Pan-Coronavirus Vaccine Candidate

September 2023: Initial data from Phase 1 study of VBI-2901 reported – the first clinical data from a pan-coronavirus vaccine candidate
VBI-2901 demonstrated vaccine benefit – reflected as boosting of and/or greater durability of antibody titer maintenance:
All participants saw boosting and/or high neutralizing antibody responses against a panel of COVID-19 variants and two animal coronaviruses
Participants with lower baseline antibody titers, reflecting a higher-risk population, saw the greatest boosting effect (5-14x strain-dependent boosting)
Durability benefit observed regardless of baseline antibody levels, with only about 25% reduction in geometric mean titer (GMT) against the Wuhan strain after 5 months vs. peak responses – compared to an approximate 77% decline in GMT against the Wuhan strain vs. peak responses to a licensed mRNA vaccine [Gilboa M, 2022]1
Q1 2024: Additional durability and breadth data from the Phase 1 study expected
Funds from existing partners, including the Canadian government and the Coalition for Epidemic Preparedness Innovations (CEPI) are available to fund the next phase of clinical development
Novel mRNA-Launched eVLP (MLE) Technology Platform

October 2023: Development of a novel mRNA-launched eVLP (MLE) technology platform announced, supported by preclinical data that have demonstrated significant immunologic and manufacturing benefits
MLE technology enables the manufacture of particulate vaccines, capable of driving polyfunctional B-cell and T-cell activation, on accelerated timelines, similar to other mRNA vaccine production timelines
New platform has the potential to be leveraged across infectious disease, cancer, and allergic and autoimmune disease indications
Third Quarter 2023 Financial Results

Cash Position: VBI ended the third quarter of 2023 with $35.5 million in cash as compared with $62.6 million in cash as of December 31, 2022.
Revenues, net: Revenues, net for the third quarter of 2023 were $6.6 million as compared to $0.3 million for the same period in 2022. The revenue increase was a result of an increase in product sales of PreHevbrio in the U.S. and of PreHevbri to our partner, Valneva, in Europe, in addition to the license revenue and R&D services revenue associated with the HBV license agreement, expanded in July 2023, with Brii Bio.
Cost of Revenues: Cost of revenues was $2.5 million in the third quarter of 2023 as compared to $2.7 million in the third quarter of 2022. The decrease in the cost of revenues was due to increased product sales, offset by lower direct labor costs as a result of the recent organization changes that reduced our internal workforce.
Research and Development (R&D): R&D expenses for the third quarter of 2023 were $1.5 million as compared to $5.0 million for the third quarter of 2022. R&D expenses were offset by $2.7 million in the third quarter of 2023 and $2.4 million in the third quarter of 2022 due to government grants and funding arrangements.
Sales, General, and Administrative (SG&A): SG&A expenses for the third quarter of 2023 were $9.0 million as compared to $14.2 million for the same period in 2022. The decrease in SG&A expenses was mainly a result of the recent organizational changes that reduced our internal workforce, as announced in April 2023, the redefined deployment strategy of our U.S. commercial field force, and a reduction in activity-based commercial expenses related to PreHevbrio.
Net Cash Used in Operating Activities: Net cash used in operating activities for the nine months ended September 30, 2023, was $48.8 million compared to $54.6 million for the same period in 2022. The decrease in cash outflows is largely a result of non-cash reconciling items, mainly impairment charges and unrealized foreign exchange loss, and the change in operating working capital, most notably in inventory, other current assets, accounts payable, deferred revenues, and other current liabilities. As announced on April 4, 2023, VBI implemented cost saving measures that are expected to reduce operating expenses from normal business in the second half of 2023 by 30-35% compared to the second half of 2022.
Net Loss and Net Loss Per Share: Net loss and net loss per share for the third quarter of 2023 were $20.4 million and $1.01, respectively, compared to a net loss and net loss per share of $25.2 million and $2.93 for the third quarter of 2022, respectively.
Net Loss, Excluding Impairment Charges and Foreign Exchange Loss, and Net Loss Per Share, Excluding Impairment Charges and Foreign Exchange Loss: Net loss, excluding impairment charges and foreign exchange loss, and net loss per share, excluding impairment charges and foreign exchange loss, for the third quarter of 2023 were $8.0 million and $0.38, respectively, compared to $22.5 million and $2.62 for the third quarter of 2022, respectively. See "Non-GAAP Financial Information" below for additional information regarding this non-GAAP financial measure, and "GAAP to Non-GAAP Reconciliation" for a reconciliation of this non-GAAP financial measure to net loss and net loss per share.
Impairment charges and foreign exchange loss for the third quarter of 2023 were $3.6 million and $8.8 million, respectively, as compared to none and $2.7 million for the third quarter of 2022. Certain intercompany loans between the Company and its subsidiaries are denominated in a currency other than the functional currency of each entity. The primary driver of the increase in foreign exchange loss was the impact of the relative strengthening of the U.S. and Canadian Dollars against the New Israeli Shekel upon translation of these intercompany loans.

On November 14, 2023 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 third quarter ended September 30, 2023, and provided an overview of recent developments (Press release, UroGen Pharma, NOV 14, 2023, View Source [SID1234637642]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"During the third quarter, UroGen achieved several notable milestones, including announcement of unprecedented positive results from our ENVISION and ATLAS Phase 3 trials of UGN-102 in LG-IR-NMIBC," said Liz Barrett, President, and Chief Executive Officer of UroGen. "Those seminal events paved the way for our recent pre-NDA meeting with the FDA where we aligned with the Agency on an efficient, rolling NDA review for UGN-102 starting in 2024. If approved, UGN-102 will be the first medicine approved for this patient population. The NDA will leverage the full strength of our clinical data with ENVISION as the pivotal trial and underscores our unwavering commitment to transforming the LG-IR-NMIBC treatment landscape, as we strive to reduce recurrence rates and minimize the need for multiple surgeries in this highly underserved patient population."

Business Highlights:

UGN-102 (mitomycin) for intravesical solution:

Announced agreement with the FDA that the current development plan evaluating duration of response at 12 months from the pivotal ENVISION trial will support submission of an NDA for the treatment of LG-IR-NMIBC. The FDA also agreed to a rolling review, allowing for early submission of the Chemistry, Manufacturing and Controls (CMC) sections of the NDA, presently slated for January 2024.

Both ENVISION and ATLAS Phase 3 clinical trials met their primary endpoints in treating LG-IR-NMIBC.

ENVISION demonstrated an unprecedented 79.2% complete response rate (CRR) among 242 patients at three months after first instillation of UGN-102. Additional data evaluating the key secondary endpoint of duration of response is expected in Q2 2024.

The ATLAS trial met its primary endpoint of disease-free survival, with topline results demonstrating a reduced risk of recurrence, progression, or death by 55% for UGN-102 ± TURBT. ATLAS also demonstrated a 64.8% CRR at three months for patients who only received UGN-102, compared to 63.6% for those patients who only received TURBT. The estimated probability of remaining disease free 15-months after randomization was 72% for UGN-102 ± TURBT and 50% for TURBT monotherapy (hazard ratio 0.45).

Accepted abstracts at the 2023 Society of Urologic Oncology Annual Meeting

Late-Breaking Podium Presentation
Urothelial Cancer Session I: Primary chemoablation for recurrent low grade intermediate risk (LG IR) NMIBC: The ENVISION trial
Speaker: Sandip Prasad, M.D., M.Phil., Director of Genitourinary Surgical Oncology, Morristown Hospital/Atlantic Health System, NJ
Date and Time: November 30, 2023 at 12:04-12:09 PM ET

Digital Poster #: 132
Session: Treatment of low-grade intermediate-risk non muscle invasive bladder cancer with UGN-102 ± transurethral resection of bladder cancer tumor (TURBT) monotherapy: the Phase 3 ATLAS trial
Date and Time: November 30, 2023 at 2:15-3:15 PM ET
JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC):

Generated quarterly net product revenue of $20.9 million for the third quarter of 2023, representing ~30% growth over the third quarter of 2022.

Activated sites on November 1, 2023 were 1,088, compared to 1,058 on August 1, 2023, while repeat accounts on November 1, 2023 were 296, compared to 267 on August 1, 2023.

A retrospective study titled, The Ablative Effect of Mitomycin Reverse Thermal Gel: Expanding the Role for Nephron Preservation Therapy in Low Grade Upper Tract Urothelial Carcinoma, published in Urologic Oncology: Seminars and Original Investigations online aimed to explore alternatives to nephroureterectomy for kidney function preservation and assess JELMYTO’s effectiveness in treating larger volume disease. Findings indicated that there were no significant differences in disease-free rates between complete ablation (78.6%), partial ablation (57.6%), or biopsy-only (66.7%) groups during the initial URS (p=0.15). Additionally, tumor size before JELMYTO induction did not significantly impact disease-free rates (p=0.09).
Third Quarter 2023 Financial Results:

JELMYTO Revenue: UroGen reported net product revenue of JELMYTO for the third quarter 2023 of $20.9 million, compared to $16.1 million in the third quarter of 2022.

R&D Expense: Research and development expenses for the third quarter 2023 were $10.2 million, including non-cash share-based compensation expense of $0.4 million as compared to $13.1 million, including non-cash share-based compensation expense of $0.6 million, for the same period in 2022.

SG&A Expense: Selling, general and administrative expenses for the third quarter 2023 were $21.8 million, including non-cash share-based compensation expense of $1.8 million. This compares to $19.1 million, including non-cash share-based compensation expense of $1.8 million, for the same period 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 for the third quarter 2023, compared to $4.8 million for the same period in 2022.

Interest Expense on Long-Term Debt: Interest expense related to the $100 million term loan facility with funds managed by Pharmakon Advisors was $3.8 million for the third quarter of 2023, compared to $2.7 million for the same period last year.

Net Loss: UroGen reported a net loss of $21.9 million, or basic and diluted net loss per ordinary share of $0.68, for the third quarter 2023 as compared to $25.8 million, or basic and diluted net loss per ordinary share of $1.13, for the same period in 2022.

Cash & Cash Equivalents: As of September 30, 2023, cash, cash equivalents and marketable securities totaled $153.9 million.

2023 Revenue, Operating Expense and RTW Expense Guidance: The Company reiterates anticipated full year 2023 net product revenues from JELMYTO to be in the range of $76 to $86 million. The Company also reiterates anticipated full year 2023 operating expenses in the range of $135 to $145 million, including non-cash share-based compensation expense of $6.0 to $11.0 million, subject to market conditions. The Company also reiterates anticipated full year 2023 non-cash financing expense related to the prepaid obligation to RTW Investments in the range of $21.0 to $26.0 million. Of this amount approximately $9.9 to $11.2 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)

September 30, 2023

December 31, 2022

Cash and cash equivalents and marketable securities

$

153,926

$

99,963

Total assets

$

193,633

$

135,619

Total liabilities

$

235,626

$

224,980

Total shareholders’ deficit

$

(41,993

)

$

(89,361

)

UROGEN PHARMA LTD.

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

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

(Unaudited)

Three months ended September 30,

Nine months ended September 30,

2023

2022

2023

2022

Revenue

$

20,852

$

16,097

$

59,183

$

46,265

Cost of revenue

2,367

2,020

7,075

5,391

Gross profit

18,485

14,077

52,108

40,874

Operating expenses:

Research and development expenses

10,230

13,093

34,312

38,429

Selling, general and administrative expenses

21,755

19,071

68,723

61,204

Total operating expenses

31,985

32,164

103,035

99,633

Operating loss

(13,500

)

(18,087

)

(50,927

)

(58,759

)

Financing on prepaid forward obligation

(5,479

)

(4,819

)

(16,047

)

(16,478

)

Interest expense on long-term debt

(3,815

)

(2,694

)

(11,129

)

(5,215

)

Interest and other income, net

906

478

1,941

604

Loss before income taxes

$

(21,888

)

$

(25,122

)

$

(76,162

)

$

(79,848

)

Income tax expense

9

(709

)

(66

)

(1,066

)

Net loss

$

(21,879

)

$

(25,831

)

$

(76,228

)

$

(80,914

)

Statements of Comprehensive Loss

Net Loss

$

(21,879

)

$

(25,831

)

$

(76,228

)

$

(80,914

)

Other Comprehensive Income (Loss)

Unrealized gain (loss) on investments

20

(99

)

(27

)

(130

)

Comprehensive Loss

$

(21,859

)

$

(25,930

)

$

(76,255

)

$

(81,044

)

Net loss per ordinary share basic and diluted

$

(0.68

)

$

(1.13

)

$

(2.89

)

$

(3.56

)

Weighted average shares outstanding, basic and diluted

32,298,182

22,798,263

26,358,719

22,711,686

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 investigational drug formulation of mitomycin in Phase 3 development for the treatment of low-grade intermediate risk NMIBC. Utilizing the RTGel Technology Platform, UroGen’s proprietary 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. The Company presented positive results from the ENVISION and ATLAS Phase 3 trials with UGN-102 for the treatment of low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) in July 2023 and assuming positive secondary endpoint data from the ENVISION study, is advancing a rolling NDA review anticipated to commence in January 2024.

About the Phase 3 ENVISION Trial

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as primary chemoablative therapy in patients with low-grade, intermediate-risk NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the complete response rate at the 3-month assessment after the first instillation, and the key secondary endpoint will evaluate durability over time in patients who achieved a complete response at the three-month assessment. Based on discussions with the FDA, and assuming positive secondary endpoint findings, UroGen anticipates submitting an NDA for UGN-102 in 2024. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550)

About the Phase 3 ATLAS Trial

ATLAS was a global, open-label, randomized controlled Phase 3 trial designed to assess the efficacy and safety of UGN-102, with or without TURBT, vs. TURBT alone in patients diagnosed with LG-IR-NMIBC. The trial enrolled 282 patients in clinical sites in the U.S., Europe and Israel. Patients were randomized 1:1 to either UGN-102 + / – TURBT or TURBT. Patients in the UGN-102 arm were treated with six weekly intravesical instillations of UGN-102. At the 3-month time point, patients were assessed for response. Patients who demonstrated a complete response to either UGN-102 or TURBT, were assessed for long-term follow-up for evidence of recurrence. Patients who demonstrated presence of persistent disease at 3-months, in either arm, underwent a TURBT and continued for long-term follow-up for evidence of recurrence. The primary endpoint of the study is disease-free survival. Learn more about the ATLAS trial at www.clinicaltrials.gov (NCT04688931)

On November 14, 2023 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported financial results for the third quarter ended September 30, 2023, and recent business progress (Press release, TransCode Therapeutics, NOV 14, 2023, View Source [SID1234637641]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In the third quarter of 2023, we successfully completed a follow-on public offering in a very difficult biotech market as we continue our clinical study with our lead therapeutic candidate, an RNA targeted therapeutic candidate for treating metastatic disease," said Michael Dudley, co-founder, president and Chief Executive Officer of TransCode. "We were excited to dose our first patient in our Phase 0 clinical trial with TTX-MC138 in cancer patients with advanced solid tumors for which further enrollment is underway.

TransCode co-founder and Chief Technology Officer, Dr. Zdravka Medarova, commented, "We also announced encouraging preclinical data in glioblastoma multiforme (GBM) with our lead candidate. In addition, we published results of a preclinical study showing that inhibition of microRNA-10b, the therapeutic target of TTX-MC138, in breast cancer cells impaired the capacity of cancer stem cells to create new tumors and become metastatic. We believe these findings are important because cancer stem cells have long been known to play a critical role in cancer initiation, metastasis, recurrence, and resistance to therapy. Therefore, we believe that inhibiting the tumor-creating capacity of these cells using TTX-MC138 has the potential to improve outcomes in patients with breast cancer that is recurrent and resistant to treatment."

Recent Business Highlights

· In July, the company announced the results of a pre-clinical study of its lead therapeutic candidate, TTX-MC138, in non-human primates, effectively engaging its target and showing favorable pharmacokinetics and tissue distribution. In the study, non-human primates (n = 4) were injected with a microdose of radiolabeled TTX-MC138 and imaged by positron emission tomography-magnetic resonance imaging (PET-MRI) to determine the pharmacokinetics and tissue distribution of the therapeutic candidate. In addition, the pharmacodynamic activity of radiolabeled TTX-MC138 following a microdose injection was determined by measuring inhibition of its target, miRNA-10b, using qRT-PCR. TTX-MC138 demonstrated a long circulation half-life and tissue distribution consistent with hepatic clearance. Importantly, even at a microdose, the therapeutic candidate showed lasting activity and significantly inhibited miRNA-10b, known to be a driver of metastatic progression in a number of cancers.

· In August, the company dosed the first patient in its First-in-Human Phase 0 clinical study. The Phase 0 trial is an open-label, single-center, microdose study intended to demonstrate delivery of the radiolabeled version of TTX-MC138 to radiographically-confirmed metastases in subjects with advanced solid tumors. Preliminary data showed that radioactivity consistent with accumulation of TTX-MC138 was detected by noninvasive imaging in the regions of the metastatic lesions previously identified by fluorodeoxyglucose (FDG)/positron emission tomography (PET) (FDG/PET). In addition, radiolabeled TTX-MC138 had pharmacokinetic behavior consistent with that expected based on non-clinical IND-enabling studies. The patient tolerated the dosing with no reported adverse reactions. Metabolite analysis indicated circulation of intact radiolabeled TTX-MC138 for more than 20 hours, equivalent to that predicted by Drug Metabolism and Pharmacokinetics (DMPK) modelling, and that the drug candidate analyzed in the blood was identical to that of the manufactured drug candidate, demonstrating in vivo stability. Complete analysis of data from this first patient is in process and will be included in the final report for all patients enrolled in the study.

· In September, the company announced the results of a pre-clinical study of TTX-MC138 in murine models bearing human glioblastoma multiforme (GBM) tumors. In this study, the therapeutic candidate was delivered to brain tumors where it effectively engaged its target. In the study reported by TransCode, mice implanted with tumors derived from human GBM patients were treated with TTX-MC138 and imaged by magnetic resonance imaging (MRI) to determine delivery of the therapeutic candidate to the tumors. In addition, the pharmacodynamic activity of TTX-MC138 was determined by measuring inhibition of miRNA-10b using qRT-PCR. TTX-MC138 was injected intravenously and accumulated efficiently in the tumors. Importantly, the therapeutic candidate showed lasting activity and significantly inhibited miRNA-10b, known to be a driver of tumor progression in glioblastoma.

· Also, in September, the company closed an underwritten public offering of an aggregate of 16,863,000 shares of its common stock (or pre-funded warrants in lieu thereof), including the partial exercise of the underwriter’s over-allotment option. Each share of common stock (or pre-funded warrant) was sold at a public offering price of $0.51 per share (inclusive of the pre-funded warrant exercise price of $0.01 per share). All of the shares and pre-funded warrants in the offering were sold by the company. Gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses, were approximately $8.5 million.

Planned Milestones

TransCode’s goals to continue to advance its portfolio include:

· TTX-MC138

o Enroll additional patients in First-in-Human Phase 0 clinical trial intended to demonstrate quantifiable evidence of delivery of radiolabeled TTX-MC138 to metastatic lesions in advanced solid tumors; measure pharmacokinetics and biodistribution in vital organs and other tissues; potentially inform therapeutic dose levels for future trials based on Phase 0 microdose results; and potentially validate delivery for the TTX pipeline more broadly, which could open-up additional relevant RNA targets that have been previously undruggable due to challenges with RNA delivery.

○ Submission to FDA of an Investigational New Drug (IND) application for a Phase I clinical trial with TTX-MC138.

· Publication of preclinical in vivo studies supporting therapeutic candidates, TTX-RIGA and TTX-siPDL1, as well as TTX-MC138 in pancreatic adenocarcinoma.

· Continuation of discussions with potential strategic partners regarding partnerships in multiple therapeutic areas including CRISPR and intracellular delivery of proteins using TransCode’s TTX delivery platform.

· Filing for orphan drug designation for TTX-MC138 in additional tumor indications.

Third Quarter 2023 Financial Highlights

· Cash was approximately $7.5 million at September 30, 2023, compared to approximately $5.0 million at December 31, 2022.

· Research and development expense was approximately $3.3 million in the third quarter of 2023, compared to approximately $3.0 million in the third quarter of 2022.

· General and administrative expense was approximately $2.0 million in the third quarter of 2023, compared to approximately $1.9 million in the third quarter of 2022.

· Operating loss for the three months ended September 30, 2023, was approximately $5.3 million, compared to an operating loss of approximately $4.3 million in the prior year period.

Financial Guidance

TransCode expects that its cash of approximately $7.5 million as of September 30, 2023, is sufficient to fund planned operations into January 2024 but not for a full 12 months from the date of its financial statements.

On November 14, 2023 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, obesity and non-alcoholic steatohepatitis (NASH), reported financial results for the quarter ended September 30, 2023 and provided corporate updates (Press release, Terns Pharmaceuticals, NOV 14, 2023, View Source [SID1234637640]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Throughout the third quarter and in recent weeks, we made meaningful progress across all three of our clinical development programs, opening U.S. Investigational New Drug (IND) applications, both for our allosteric BCR-ABL inhibitor TERN-701 for chronic myeloid leukemia (CML) and our lead small molecule oral GLP-1 agonist TERN-601 for obesity, and releasing Phase 2 data for our thyroid hormone receptor β agonist TERN-501 from the DUET study in NASH patients. We are now preparing for a data-rich 2024, with expected proof of concept readouts from our clinical trials in CML and obesity," stated Erin Quirk, MD, president and head of research and development at Terns. "The advances we are making, which are supported by strong clinical and scientific data, give us even greater confidence in our approach to bring better chemistry to the development of small-molecule candidates with clinically validated mechanisms to address oncologic and metabolic diseases with large unmet medical needs."

"We are excited to have dosed the first participant in our first-in-human trial of TERN-601 to treat obesity as preclinical data suggest it has potential for broad metabolic benefits in obesity, oral once-daily dosing, and suitability for combination therapy. We are also looking forward to dosing the first participants in our Phase 1 trial of TERN-701 as a treatment for CML while leveraging insights from our partner’s ongoing Phase 1 trial in China to support a starting dose that appears safe and clinically active based on emerging early clinical data," added Dr. Quirk.

Recent Pipeline Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for CML
•
In October, Terns announced the Investigational New Drug (IND) clearance from the U.S. FDA and design of the CARDINAL Phase 1 clinical trial of TERN-701 for the treatment of CML
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 participants with previously treated CML
o
The dose escalation portion (Part 1) of the trial will evaluate once-daily TERN-701 monotherapy in approximately 24-36 adults living with CML to be enrolled in up to five dose cohorts; screening for Part 1 is anticipated to begin in December 2023

▪
Primary endpoints of the CARDINAL dose escalation portion include incidence of dose limiting toxicities (DLTs) during the first treatment cycle and additional measures of safety and tolerability
▪
Secondary endpoints include PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels
▪
The starting dose is 160 mg QD (once-daily), with the option to explore a lower dose of 80 mg QD
o
The dose expansion portion (Part 2) of the CARDINAL trial will initiate after dose escalation data are available and will enroll approximately 40 patients, randomized to once-daily treatment with one of two doses of TERN-701 to be selected based on data from Part 1
▪
The primary endpoint of the CARDINAL dose expansion portion is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK
•
The CARDINAL trial plans to enroll at sites in the United States, Europe and other global territories
•
Global site identification and trial start-up activities are ongoing, with interim top-line readouts from initial cohorts expected in the second half of 2024

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

•
Earlier this month, Terns announced that the first participant was dosed in the Phase 1 first-in-human clinical trial of TERN-601 for obesity
•
The Phase 1 trial is a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, PK and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or who are overweight
o
Part 1 (SAD) is a SAD study that will evaluate up to six once-daily TERN-601 dose levels in approximately 40 healthy participants
▪
The starting TERN-601 dose is 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts
o
Part 2 (MAD) of the trial will enroll approximately 72 obese and overweight healthy participants and will include cohorts incorporating titration of TERN-601 administered for 28-days at doses to be selected based on data from Part 1
•
Top-line, 28-day proof of concept weight loss data from the Phase 1 trial is expected in the second half of 2024

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

•
Phase 2a DUET trial data evaluating TERN-501 for the treatment of NASH was featured in an oral late-breaking presentation at The Liver Meeting 2023:
o
The oral presentation titled, "Topline results from a 12-week Phase 2a Trial (DUET) evaluating TERN-501, a highly selective thyroid hormone receptor (THR) β agonist, either as monotherapy or in combination with TERN-101, a nonsteroidal farnesoid X receptor (FXR) agonist, demonstrated significant reductions in MR-based liver fat content and fibroinflammation in patients with presumed NASH," was delivered by Mazen Noureddin, MD, MHSc, Professor of Medicine, Academic Institute at Houston Methodist, Director of Houston Research Institute
•
Terns reported positive top-line data from the Phase 2a DUET trial of TERN-501 for the treatment of NASH in August
o
TERN-501 met all primary and secondary endpoints
o
TERN-501 demonstrated dose dependent MRI-PDFF reductions at Week 12 as a once-daily, low dose, and combinable oral therapy
o
TERN-501 (6 mg) showed statistically significant mean relative liver fat content reduction of 45% as assessed by MRI-PDFF with 64% of patients achieving >30% PDFF reduction
o
All TERN-501 doses were well-tolerated with no gastrointestinal and no cardiovascular safety signals

Corporate Updates

•
In August 2023, Terns announced the departure of Senthil Sundaram, the Company’s former chief executive officer, for health reasons. Terns is conducting an ongoing search for a permanent chief executive officer. In the interim, Dr. Quirk continues to assume day-to-day leadership of the Company and serve as principal executive officer. In addition, the Board has engaged board director, Jill M. Quigley, JD as senior advisor and strategy officer on an interim basis until a permanent chief executive officer is appointed.

Third Quarter 2023 Financial Results

•
Cash Position: As of September 30, 2023, cash, cash equivalents and marketable securities were $266.6 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 $14.8 million for the quarter ended September 30, 2023, as compared with $12.2 million for the quarter ended September 30, 2022.
•
General and Administrative (G&A) Expenses: G&A expenses were $18.4 million for the quarter ended September 30, 2023, as compared with $5.1 million for the quarter ended September 30, 2022.
•
Net Loss: Net loss was $29.8 million for the quarter ended September 30, 2023, as compared with $16.8 million for the quarter ended September 30, 2022.

On November 14, 2023 Sigyn Therapeutics, Inc. ("Sigyn" or the "Company") (OTCQB: SIGY), a development-stage medical technology company, reported its financial results for the third quarter ended September 30, 2023 (Press release, Sigyn Therapeutics, NOV 14, 2023, View Source [SID1234637639]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

During the quarter, the Company continued its plan to initiate first-in-human studies of Sigyn TherapyTM and further advanced its endeavors to develop pipeline technologies to enhance the performance of cancer therapies. The initial treatment indication of Sigyn TherapyTM is being directed toward end-stage renal disease (ESRD) patients with endotoxemia, a condition that is highly prevalent and associated with increased mortality in the ESRD population. The Company has identified three clinical site locations and is working with principal investigators to finalize the study protocol. Once finalized, the Company intends to submit an Investigational Device Exemption (IDE) to The U.S. Food and Drug Administration (FDA) requesting permission to enroll up to 15 ESRD subjects with the primary objective to demonstrate the safety of Sigyn TherapyTM.

Summary of Third Quarter 2023 Financial Results

For the quarter ended September 30, 2023, the Company had a loss from operations of approximately $642,814, compared to an operating loss of approximately $533,647 for the comparable period of 2022. The Company’s net loss for the 2023 third quarter was approximately $905,726 or approximately $0.02 per share, compared to a net loss of approximately $726,509, or approximately $0.02 per share, for the comparable period in 2022.

For complete financial results, please see Sigyn Therapeutics’ filings at www.sec.gov, and on the Company’s website at www.SigynTherapeutics.com under "Financial Info" in the Investors section.