On May 14, 2025 Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, reported updated, positive data from the Phase 1 ENABLE clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia (CML) in an abstract accepted for an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress taking place June 12-15 in Milan, Italy, and virtually (Press release, Enliven Therapeutics, MAY 14, 2025, View Source [SID1234653093]). Updated data will be presented during an oral presentation at the conference on Friday, June 13, at 5 p.m. CEST/11 a.m. ET. Enliven management will host a webcast and conference call to discuss the data on Friday, June 13, at 7:30 p.m. CEST/1:30 p.m. ET.

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ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion, the oncogenic driver for patients with CML. Data presented at EHA (Free EHA Whitepaper) will be from the ongoing ENABLE Phase 1a/1b clinical trial, which enrolled patients with CML that have failed, are intolerant to, or are not a candidate for, available therapies known to be active for treatment of their CML (NCT05304377).

"We are strongly encouraged by the consistent efficacy, safety and tolerability data from the ongoing ENABLE trial in heavily pretreated patients with CML," said Helen Collins, M.D., Chief Medical Officer of Enliven. "These data continue to demonstrate the potential for ELVN-001 to achieve a best-in-class profile compared to the available active-site TKIs. We look forward to providing additional updates at the EHA (Free EHA Whitepaper) Congress in June."

Abstract Highlights

Patient Demographics

As of the cutoff date of January 21, 2025, 74 patients have been enrolled in the ongoing Phase 1 trial across dose levels from 10-160 mg daily and the vast majority of patients (82%) remain on study with a median treatment duration of ~26 weeks.
Patients enrolled continue to be heavily pretreated, with 66% having received three or more prior tyrosine kinase inhibitors (TKIs), including ponatinib (45%) and asciminib (57%).
Updated Efficacy

Of the enrolled patients, 36 with typical transcripts and without T315I mutations were evaluable for molecular response by 24 weeks.
16 of 36 (44%) evaluable patients were in major molecular response (MMR) by 24 weeks, with 7 of 27 (26%) achieving and 9 of 9 (100%) maintaining MMR.
Of those resistant to their last TKI, 10 of 25 (40%) were in MMR by 24 weeks.
Of those previously treated with asciminib or ponatinib, 9 of 25 (36%) were in MMR by 24 weeks, including one with a known asciminib resistance mutation (A337T).
All patients who achieved or maintained MMR were still in MMR at the time of data cutoff.
These data continued to compare favorably to precedent Phase 1 MMRs for approved BCR::ABL1 TKIs, particularly given the more heavily pre-treated patient population in the ELVN-001 clinical trial.
Updated Safety

ELVN-001 remains well-tolerated across all doses, consistent with its selective kinase profile.
Dose interruptions and reductions occurred in less than 10% and less than 5% of patients, respectively.
The maximum tolerated dose was not reached.
Details of the oral presentation are as follows:
Title: ENABLE: A Phase 1a/1b Study of ELVN-001, a selective active site inhibitor of BCR::ABL1, in patients with previously treated CML
Presenter: Andreas Hochhaus, M.D.
Session Title: s425 Novel approaches of CML treatment
Location: Coral 2
Abstract Number: S165
Presentation Date/Time: June 13, 5 p.m. CEST / 11 a.m. ET

The abstract is available on the EHA (Free EHA Whitepaper) website. Following the presentation, a copy will be available on the "Program Presentations & Publications" section of the Company’s website at www.enliventherapeutics.com.

Webcast and Conference Call Information
Enliven will host a conference call with management on June 13, 2025, at 7:30 p.m. CEST/1:30 p.m. ET. To access the call, please dial +1 (800) 803-6955 (domestic) or (240) 220-9050 (international), and reference participant ID 631-128-259 at least 10 minutes prior to the start time and ask to be joined to the Enliven call. Accompanying slides and a link to the webcast will be available in the Investors section of the Enliven website at View Source To participate in the live event, please register using this link. An archived webcast will be available following the event.

About the ENABLE Trial
The ENABLE study (NCT05304377) is a Phase 1 study of ELVN-001 in patients with previously treated CML. The trial is currently in Phase 1a/1b development and is a dose escalation and expansion trial designed to evaluate safety and tolerability and to determine the recommended dose for further clinical evaluation of ELVN-001 in patients with CML with and without T315I mutations that is relapsed, refractory or intolerant to TKIs. Secondary endpoints include pharmacokinetics, MMR by central quantitative reverse transcriptase polymerase chain reaction, duration of MMR, BCR::ABL1 transcript levels and complete hematologic response. Enliven is preparing for the potential start of a pivotal trial for ELVN-001 in 2026.

About ELVN-001
ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion, the oncogenic driver for patients with chronic myeloid leukemia. As a highly selective active site inhibitor, ELVN-001 has a mechanism of action that is complementary to allosteric BCR::ABL1 inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was also designed to have activity against the T315I mutation, the most common BCR::ABL1 mutation, which confers resistance to nearly all approved TKIs, as well as activity against mutations known to confer resistance to allosteric BCR::ABL1 inhibitors.

On May 14, 2025 AbbVie (NYSE: ABBV) reported that EMRELIS (telisotuzumab vedotin-tllv) has been granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression (OE) who have received a prior systemic therapy (Press release, AbbVie, MAY 14, 2025, View Source [SID1234653092]). High c-Met protein overexpression is defined as ≥ 50% of tumor cells with strong (3+) staining as determined by an FDA-approved test.2,3

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This indication is approved based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). EMRELIS is a c-Met-directed antibody-drug conjugate (ADC) and the first and only treatment approved for this patient population. ADCs are designed to target unique biomarkers such as the c-Met protein and deliver a potent ‘payload’ directly to the biomarker-expressing cell.

Approximately 85% of lung cancers are classified as NSCLC4,5 and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths throughout the world.1 The c-Met protein is found to be overexpressed in approximately 25% of advanced EGFR wild type, non-squamous NSCLC patients and is associated with poor prognosis.2,6-12 Approximately half of these patients have high c-Met overexpression, defined as ≥ 50% of tumor cells with strong (3+) staining by immunohistochemistry (IHC) test.2

"We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes," said Jonathan Goldman, MD, professor of medicine, director of thoracic oncology clinical trials, UCLA. "People with c-Met overexpressing NSCLC have poor prognosis and limited treatment options, and EMRELIS is a first-in-class ADC that can address a critical unmet need for this patient population."

"EMRELIS, AbbVie’s first internally developed solid tumor medicine and our first solid tumor FDA approval in lung cancer, is a testament to our commitment to develop cancer therapies that aim to improve the course of treatment for patients facing this challenging disease," said Roopal Thakkar, MD, executive vice president, research and development, chief scientific officer, AbbVie. "Leveraging advanced technology and data science, we are growing our ADC portfolio designed to deliver the right medicines to the right patients in need across a range of difficult-to-treat tumors."

"Despite the progress we have seen in the treatment of lung cancer, we need more options for people whose treatments stop working," said Upal Basu Roy, PhD, MPH, executive director of research, LUNGevity Foundation, a leading lung cancer nonprofit organization. "This approval is a welcomed targeted therapy for those with high c-Met protein overexpressing late-stage, non-small cell lung cancer who have seen very limited treatment innovation in the last decade."

The FDA accelerated approval is supported by data from the Phase 2 LUMINOSITY study (NCT03539536), a study designed to characterize the efficacy and safety of EMRELIS in c-Met overexpressing advanced NSCLC populations. Findings from the study showed patients with high c-Met protein overexpression (n=84) who received EMRELIS demonstrated a 35% (95% CI: 24, 46) Overall Response Rate (ORR) and Duration of Response (DOR) with a median of 7.2 months (95% CI: 4.2, 12). The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium.2

In December 2021, the FDA granted EMRELIS Breakthrough Therapy Designation (BTD) based on Phase 2 LUMINOSITY study data.

EMRELIS is being further evaluated as a monotherapy in patients with previously treated c-Met overexpressing NSCLC in the randomized Phase 3 confirmatory global study TeliMET NSCLC-01. Enrollment in the study is underway and continues across global clinical trial sites. Additional information on clinical trials for EMRELIS is available at www.clinicaltrials.gov.

The FDA has also approved the Roche VENTANA MET (SP44) RxDx Assay, the only IHC companion diagnostic that identifies patients eligible for treatment with EMRELIS. To determine c-Met protein biomarker status, patients can be tested on recent or archived tissue.

About the LUMINOSITY Trial
The LUMINOSITY trial (NCT03539536) is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for telisotuzumab vedotin-tllv monotherapy in the second-line or third-line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).2

Patient Access and Support
AbbVie is committed to helping people access EMRELIS and other medicines, including offering a patient support program and co-pay card that may reduce out-of-pocket costs to as little as $0 per month for eligible, commercially insured patients. Financial support might also include reimbursement for out-of-pocket costs related to IV administration. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides EMRELIS at no charge to those who qualify. More information can be found at www.AbbVie.com/PatientAccessSupport.

About EMRELIS
EMRELIS (telisotuzumab vedotin-tllv) is a first-in-class c-Met-directed antibody-drug conjugate (ADC) comprising of a c-Met-binding antibody, cleavable linker and the monomethyl auristatin E (MMAE) payload designed to target c-Met expressing cells.3 The c-Met protein is a receptor tyrosine kinase that can be overexpressed in NSCLC and is associated with poor prognosis.2, 6-12

EMRELIS (telisotuzumab vedotin-tllv) U.S. Uses and Important Safety Information3

What is EMRELIS?
EMRELIS is a prescription medicine used to treat adults with non-squamous non-small cell lung cancer (NSCLC):

that has spread to areas near the lungs (locally advanced) or to other parts of the body (metastatic), and
whose tumors have high c-Met protein overexpression, and
who have received a prior treatment.
Your healthcare provider will perform a test to make sure EMRELIS is right for you.

It is not known if EMRELIS is safe and effective in children.

IMPORTANT SAFETY INFORMATION
What is the most important information I should know about EMRELIS?
EMRELIS can cause serious side effects, including:

Nerve problems in your hands or feet (peripheral neuropathy). Nerve problems are common during treatment with EMRELIS and can also be severe. Tell your healthcare provider if you develop any new or worsening signs or symptoms of nerve problems, including:

numbness
tingling
burning sensation

pain or discomfort
muscle weakness
difficulty walking
Lung problems. EMRELIS can cause lung problems that may be severe, life-threatening or that may lead to death. Tell your healthcare provider right away if you develop new or worsening lung symptoms, including:

cough
trouble breathing or shortness of
breath

fever
wheezing
Eye problems. Your healthcare provider may send you to an eye care professional to check your eyes if you develop eye problems. Tell your healthcare provider right away if you develop any new or worsening eye problems or vision changes, including:

blurred vision
dry eyes
sensitivity to light

eye pain or swelling
eye redness
Infusion-related reactions. EMRELIS can cause infusion reactions that can be severe or life-threatening. Tell your healthcare provider right away if you develop any signs and symptoms of infusion reactions, including:

itching or rash
shortness of breath or wheezing
flushing
chest discomfort
fever

back pain
chills
headache
nausea or vomiting
feel like passing out
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with EMRELIS and may provide treatment for your side effects. Your healthcare provider may also need to change your dose, temporarily stop, or completely stop treatment with EMRELIS if you have severe side effects.

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

have a history of nerve problems
have lung or breathing problems other than your lung cancer
have eye problems
have liver problems
are pregnant or plan to become pregnant. EMRELIS can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with EMRELIS.
You should use effective birth control (contraception) during treatment and for 2 months after your last dose of EMRELIS.
Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EMRELIS.
Males with female partners who are able to become pregnant:
You should use an effective birth control during treatment and for 4 months after taking the last dose of EMRELIS
are breastfeeding or plan to breastfeed. It is not known if EMRELIS passes into your breast milk. Do not breastfeed during treatment with EMRELIS and for 1 month after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking certain medicines with EMRELIS may increase your risk of side effects.

How will I receive EMRELIS?

Your healthcare provider will give you EMRELIS into your vein through an intravenous (IV) line over 30 minutes.
EMRELIS is given 1 time every 2 weeks.
Your healthcare provider will decide how many infusions of EMRELIS you will receive.
What are the possible side effects of EMRELIS?
EMRELIS can cause serious side effects. See ‘What is the most important information I should know about EMRELIS?"

The most common side effects of EMRELIS include:

feeling tired
decreased appetite
swelling in the feet, ankles, legs, or hands
The most common severe abnormal laboratory tests results of EMRELIS include:

decreased white blood cell counts
increased blood sugar levels
increased blood liver enzyme levels
decreased blood phosphorus levels

decreased blood sodium levels
decreased red blood cell counts
decreased blood calcium levels
EMRELIS may cause fertility problems in females and males, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of EMRELIS.

Call your doctor for medical advice about side effects.

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.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/PatientAccessSupport to learn more.

Please see the Full Prescribing Information and Medication Guide.

On May 14, 2025 Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, reported financial results for the first quarter ended March 31, 2025, and provided a business update, including highlights of pipeline progress (Press release, Enliven Therapeutics, MAY 14, 2025, View Source [SID1234653091]).

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"We are very pleased with the continued progress of ELVN-001 and the data that was just released in the EHA (Free EHA Whitepaper) abstract. We continue to gain confidence and momentum in the program as the efficacy, safety and tolerability data consistently compare favorably to the approved BCR::ABL inhibitors. We are excited to share further updated data at EHA (Free EHA Whitepaper) next month," said Sam Kintz, Co-founder and Chief Executive Officer of Enliven. "Looking towards the rest of the year, we remain focused on clinical execution as we prepare for the potential start of a pivotal trial for ELVN-001 in 2026."

Recent Research and Development Highlights and Upcoming Milestones

ELVN-001 is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion

Today, the Company announced positive updated data from the ongoing ENABLE Phase 1 clinical trial evaluating ELVN-001 in patients with previously treated chronic myeloid leukemia (CML) (NCT05304377) in an abstract that was accepted for an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress.
As of the cutoff date for the abstract (January 21, 2025), 74 patients were enrolled in the trial across dose levels from 10-160 mg daily, and the vast majority of patients (82%) remain on study with a median treatment duration of ~26 weeks.
16 of 36 (44%) evaluable patients were in major molecular response (MMR) by 24 weeks, with 7 of 27 (26%) achieving and 9 of 9 (100%) maintaining MMR.
ELVN-001 continues to demonstrate a favorable safety and tolerability profile, consistent with its selective kinase profile.
These data continue to compare favorably to precedent Phase 1 trials of the approved BCR::ABL1 tyrosine kinase inhibitors (TKIs), particularly given the more heavily pre-treated patient population in the ELVN-001 clinical trial.
An oral presentation will be delivered at the EHA (Free EHA Whitepaper) 2025 Congress, taking place June 12–15 in Milan, Italy, and virtually, and will highlight updated results, including data from additional patients and longer treatment duration.
Enliven will also host a webcast and conference call at 1:30 p.m. ET on Friday, June 13, 2025, to discuss the updated data. Details of the webcast are posted on the Upcoming Events page of the Company’s website.
ELVN-002 is a potent, highly selective, central nervous system (CNS) penetrant and irreversible HER2 inhibitor with activity against wild type HER2 and various HER2 mutations

The Company dosed the first patient in its Phase 1 exploratory cohort evaluating ELVN-002 in combination with trastuzumab deruxtecan (NCT05650879) and progressed its Phase 1 trial evaluating ELVN-002 in combination with trastuzumab in HER2+ colorectal cancer (NCT06328738).
To prioritize the advancement of ELVN-001 and its upcoming pivotal trial, the Company plans to explore strategic alternatives for the ELVN-002 program and does not intend to pursue its development beyond 2025, which is expected to extend cash runway into late 2027.
First Quarter 2025 Financial Results

Cash Position: As of March 31, 2025, the Company had cash, cash equivalents and marketable securities totaling $289.6 million, which is expected to provide cash runway into late 2027.
Research and development (R&D) expenses: R&D expenses were $24.9 million for the first quarter of 2025, compared to $20.0 million for the first quarter of 2024.
General and administrative (G&A) expenses: G&A expenses were $6.8 million for the first quarter of 2025, compared to $6.0 million for the first quarter of 2024.
Net Loss: Enliven reported a net loss of $28.5 million for the first quarter of 2025, compared to a net loss of $22.7 million for the first quarter of 2024.

On May 14, 2025 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported financial results for the first quarter ended March 31, 2025, and provided a corporate update (Press release, Theriva Biologics, MAY 14, 2025, View Source [SID1234653088]).

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"We have started 2025 with outstanding clinical progress," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "The VIRAGE Phase 2b clinical trial of VCN-01 (zabilugene almadenorepvec) with gemcitabine/nab-paclitaxel in newly diagnosed metastatic pancreatic cancer patients achieved its primary survival and safety endpoints, highlighting the potential therapeutic benefits of our oncolytic virus platform. We are working to scale up manufacturing and finalize the design of a Phase 3 trial of VCN-01 with gemcitabine/nab-paclitaxel which if successful, may allow us to deliver this innovative treatment option to patients suffering this fatal disease."

Recent Highlights and Anticipated Milestones

VCN-01

Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC):

As recently announced, mPDAC patients treated with VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy had increased overall survival (OS), progression free survival (PFS), and duration of response (DOR) compared to patients treated with gemcitabine/nab-paclitaxel SoC.
VCN-01 was well-tolerated, with transient and reversible adverse events (AEs).
The increase in OS was greater for patients who received 2 doses of VCN-01 and 4 or more cycles of gemcitabine/nab-paclitaxel compared with patients who received 4 or more cycles of gemcitabine/nab-paclitaxel SoC alone, suggesting that the second dose of VCN-01 (administered 3 months after the first dose) provides a meaningful additional benefit in this treatment subgroup.
Theriva had hosted a virtual event featuring feature eminent pancreatic cancer clinician/researchers to review and discuss the data from the VIRAGE trial of VCN-01. To access the replay of the event, click HERE.
The Company is currently working to scale up manufacturing of VCN-01 and finalizing the design of a potential Phase 3 confirmatory trial for VCN-01 in mPDAC.
SYN-004

Allogeneic hematopoietic cell transplant (HCT):

As recently announced, data from a Phase 1b/2a trial investigating SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD) was presented at the Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global) in April.
Corporate Updates

As recently announced, Theriva closed a public offering of 6,818,180 shares of common stock (or pre-funded warrants in lieu thereof) and warrants to purchase up to 6,818,180 shares of common stock at a combined offering price of $1.10 per share and accompanying warrant (the "Offering"). The Company received aggregate gross proceeds of approximately $7.5 million, before deducting placement agent fees and other offering expenses. The warrants have an exercise price of $1.10 per share, are exercisable immediately and expire five years from the issuance date.
The Company intends to use the net proceeds from the Offering primarily for working capital and general corporate purposes, including for research and development, and manufacturing scale-up of VCN-01 for a potential Phase 3 clinical trial.
First Quarter Ended March 31, 2025 Financial Results

General and administrative expenses decreased to $1.4 million for the three months ended March 31, 2025, from $1.9 million for the three months ended March 31, 2024. This decrease of 25% is primarily comprised of the decrease in salary costs, travel, lower director and officer insurance, and a decrease in fair value of the contingent consideration adjustment. The charge related to stock-based compensation expense was $54,000 for the three months ended March 31, 2025, compared to $101,000 for the three months ended March 31, 2024.

Research and development expenses decreased to $3.0 million for the three months ended March 31, 2025, from approximately $3.5 million for the three months ended March 31, 2024. This decrease of 14% is primarily the result of lower indirect cost related to decreased VCN-01 manufacturing costs and lower clinical trial expenses related to our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, offset by slightly higher clinical trial expenses related to our VIRAGE Phase 2b clinical trial of VCN-01 in PDAC and higher patent expenses related to SYN-020. We anticipate research and development expense to increase as we complete our VIRAGE Phase 2b clinical trial of VCN-01 and plan for our Phase 3 clinical trial of VCN-01 in PDAC, advance our VCN-01 program in retinoblastoma, expand GMP scale-up manufacturing activities for VCN-01, and continue supporting our other preclinical and discovery initiatives. The charge related to stock-based compensation expense was $46,000 for the three months ended March 31, 2025, compared to $58,000 related to stock-based compensation expense for the three months ended March 31, 2024.

Other income was $93,000 for the three months ended March 31, 2025 compared to other income of $227,000 for the three months ended March 31, 2024. Other income for the three months ended March 31, 2025 is primarily comprised of interest income of $96,000 and an exchange loss of $3,000. Other income for the three months ended March 31, 2024 is primarily comprised of interest income of $228,000 and exchange loss of $1,000.

Cash and cash equivalents totaled $10 million as of March 31, 2025, compared to $11.6 million as of December 31, 2024. Subsequent to closing of the public offering on May 8 2025, the Company’s cash balance was $14.1 million.

About Pancreatic Ductal Adenocarcinoma

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma ("PDAC") accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms, so in most cases it is diagnosed in its late stages (locally advanced non-metastatic or metastatic disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

About VIRAGE

VIRAGE was a two-arm, Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. Patients were enrolled at 5 sites in the U.S. and 9 sites in Spain. In both the control and VCN-01 (zabilugene almadenorepvec) treatment arms, patients received gemcitabine/nab-paclitaxel standard-of-care chemotherapy in repeated 28-day cycles until disease progression. In the VCN-01 treatment arm only, patients were also administered intravenous VCN-01 seven-days prior to starting the first and fourth cycles of gemcitabine/nab-paclitaxel treatment (study days 1 and ~92 respectively). Primary endpoints for the trial include overall survival and VCN-01 safety/tolerability. Additional endpoints include progression free survival, duration of response, and measures of VCN-01 biodistribution, replication, and immune response. More information about the trial is available on Clinicaltrials.gov (NCT05673811), through the Spanish Clinical Trials Registry and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2022-000897-24).

About VCN-01

VCN-01 (zabilugene almadenorepvec) is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to 142 patients to date in clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.

On May 14, 2025 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported financial results for the first quarter ended March 31, 2025, and provided a corporate update (Press release, Theriva Biologics, MAY 14, 2025, View Source [SID1234653088]).

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!

"We have started 2025 with outstanding clinical progress," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "The VIRAGE Phase 2b clinical trial of VCN-01 (zabilugene almadenorepvec) with gemcitabine/nab-paclitaxel in newly diagnosed metastatic pancreatic cancer patients achieved its primary survival and safety endpoints, highlighting the potential therapeutic benefits of our oncolytic virus platform. We are working to scale up manufacturing and finalize the design of a Phase 3 trial of VCN-01 with gemcitabine/nab-paclitaxel which if successful, may allow us to deliver this innovative treatment option to patients suffering this fatal disease."

Recent Highlights and Anticipated Milestones

VCN-01

Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC):

As recently announced, mPDAC patients treated with VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy had increased overall survival (OS), progression free survival (PFS), and duration of response (DOR) compared to patients treated with gemcitabine/nab-paclitaxel SoC.
VCN-01 was well-tolerated, with transient and reversible adverse events (AEs).
The increase in OS was greater for patients who received 2 doses of VCN-01 and 4 or more cycles of gemcitabine/nab-paclitaxel compared with patients who received 4 or more cycles of gemcitabine/nab-paclitaxel SoC alone, suggesting that the second dose of VCN-01 (administered 3 months after the first dose) provides a meaningful additional benefit in this treatment subgroup.
Theriva had hosted a virtual event featuring feature eminent pancreatic cancer clinician/researchers to review and discuss the data from the VIRAGE trial of VCN-01. To access the replay of the event, click HERE.
The Company is currently working to scale up manufacturing of VCN-01 and finalizing the design of a potential Phase 3 confirmatory trial for VCN-01 in mPDAC.
SYN-004

Allogeneic hematopoietic cell transplant (HCT):

As recently announced, data from a Phase 1b/2a trial investigating SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD) was presented at the Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global) in April.
Corporate Updates

As recently announced, Theriva closed a public offering of 6,818,180 shares of common stock (or pre-funded warrants in lieu thereof) and warrants to purchase up to 6,818,180 shares of common stock at a combined offering price of $1.10 per share and accompanying warrant (the "Offering"). The Company received aggregate gross proceeds of approximately $7.5 million, before deducting placement agent fees and other offering expenses. The warrants have an exercise price of $1.10 per share, are exercisable immediately and expire five years from the issuance date.
The Company intends to use the net proceeds from the Offering primarily for working capital and general corporate purposes, including for research and development, and manufacturing scale-up of VCN-01 for a potential Phase 3 clinical trial.
First Quarter Ended March 31, 2025 Financial Results

General and administrative expenses decreased to $1.4 million for the three months ended March 31, 2025, from $1.9 million for the three months ended March 31, 2024. This decrease of 25% is primarily comprised of the decrease in salary costs, travel, lower director and officer insurance, and a decrease in fair value of the contingent consideration adjustment. The charge related to stock-based compensation expense was $54,000 for the three months ended March 31, 2025, compared to $101,000 for the three months ended March 31, 2024.

Research and development expenses decreased to $3.0 million for the three months ended March 31, 2025, from approximately $3.5 million for the three months ended March 31, 2024. This decrease of 14% is primarily the result of lower indirect cost related to decreased VCN-01 manufacturing costs and lower clinical trial expenses related to our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, offset by slightly higher clinical trial expenses related to our VIRAGE Phase 2b clinical trial of VCN-01 in PDAC and higher patent expenses related to SYN-020. We anticipate research and development expense to increase as we complete our VIRAGE Phase 2b clinical trial of VCN-01 and plan for our Phase 3 clinical trial of VCN-01 in PDAC, advance our VCN-01 program in retinoblastoma, expand GMP scale-up manufacturing activities for VCN-01, and continue supporting our other preclinical and discovery initiatives. The charge related to stock-based compensation expense was $46,000 for the three months ended March 31, 2025, compared to $58,000 related to stock-based compensation expense for the three months ended March 31, 2024.

Other income was $93,000 for the three months ended March 31, 2025 compared to other income of $227,000 for the three months ended March 31, 2024. Other income for the three months ended March 31, 2025 is primarily comprised of interest income of $96,000 and an exchange loss of $3,000. Other income for the three months ended March 31, 2024 is primarily comprised of interest income of $228,000 and exchange loss of $1,000.

Cash and cash equivalents totaled $10 million as of March 31, 2025, compared to $11.6 million as of December 31, 2024. Subsequent to closing of the public offering on May 8 2025, the Company’s cash balance was $14.1 million.

About Pancreatic Ductal Adenocarcinoma

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma ("PDAC") accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms, so in most cases it is diagnosed in its late stages (locally advanced non-metastatic or metastatic disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

About VIRAGE

VIRAGE was a two-arm, Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. Patients were enrolled at 5 sites in the U.S. and 9 sites in Spain. In both the control and VCN-01 (zabilugene almadenorepvec) treatment arms, patients received gemcitabine/nab-paclitaxel standard-of-care chemotherapy in repeated 28-day cycles until disease progression. In the VCN-01 treatment arm only, patients were also administered intravenous VCN-01 seven-days prior to starting the first and fourth cycles of gemcitabine/nab-paclitaxel treatment (study days 1 and ~92 respectively). Primary endpoints for the trial include overall survival and VCN-01 safety/tolerability. Additional endpoints include progression free survival, duration of response, and measures of VCN-01 biodistribution, replication, and immune response. More information about the trial is available on Clinicaltrials.gov (NCT05673811), through the Spanish Clinical Trials Registry and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2022-000897-24).

About VCN-01

VCN-01 (zabilugene almadenorepvec) is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to 142 patients to date in clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.