On November 28, 2023 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported a strategic restructuring to focus on continuation and expansion of development of CAN-3110 as well as the enLIGHTEN Discovery Platform, while reducing the Company’s workforce and expenses associated with enabling commercial readiness of CAN-2409 (Press release, Candel Therapeutics, NOV 28, 2023, View Source [SID1234638017]). The Company expects to present initial activity and biomarker data for repeated injections of CAN-3110 in recurrent high-grade glioma in the second half of 2024 and new data for the second drug candidate based on the enLIGHTEN Discovery Platform in Q3 2024. The Company plans to continue to collect clinical data for key readouts for CAN-2409 in non-small cell lung cancer (NSCLC), with topline overall survival data of the open label phase 2 clinical trial expected in Q2 2024; pancreatic cancer, with an update on overall survival based on an interim analysis of the randomized, open label clinical trial in Q2 2024; and prostate cancer, with topline data for both fully enrolled randomized, blinded, placebo-controlled phase 2 and phase 3 clinical trials in Q4 2024.

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!

Based on the encouraging clinical activity data for CAN-2409, the large number of patients that might benefit from this treatment, and the investments needed for commercialization, the Company plans to explore the right partnering opportunities for the future development of this asset.

To focus on delivering on the value-creating catalysts in 2024, on November 28, 2023, Candel implemented a reduction in its workforce of approximately 50%. The Company estimates that it will incur a one-time restructuring charge of approximately $0.7 million in the fourth quarter of 2023 related to severance and healthcare and related benefits for terminated employees. Candel expects that the reduction in workforce, coupled with the reduced operating costs, will enable the Company’s existing cash resources to fund its revised operating plan into the fourth quarter of 2024, enabling the achievement of key catalysts next year.

"This decision, unfortunately, impacts our workforce," said Paul Peter Tak, MD PhD FMedSci, President and CEO of Candel. "I want to express my sincere gratitude for the very important work and valuable contributions of our departing employees. They have done amazing work advancing the pipeline and developing our investigational medicines. In the current market, we need to remain laser focused on delivering on our value-creating inflections points, while managing our expenditures. We have proof of mechanism and proof of concept in each indication that we are currently pursuing, and the value created in the past years will be leveraged in the multiple data readouts planned for 2024."

About the enLIGHTEN Discovery Platform

Candel’s enLIGHTEN Discovery Platform is a systematic, iterative herpes simplex virus (HSV)-based discovery platform leveraging human biology and advanced analytics to create new multimodal biological immunotherapies for solid tumors. In October 2022, the Company announced a discovery collaboration with the University of Pennsylvania Center for Cellular Immunotherapies to identify how viral immunotherapy could enhance the efficacy of CAR-T cell therapy in solid tumors. The enLIGHTEN Discovery Platform is designed to deconvolute the complexity of the tumor microenvironment to identify druggable properties that correlate with clinical outcomes. These discoveries are rapidly translated into optimized multi-gene payloads of tumor modulators that are tailored for specific indications, disease stage, and rationally designed therapeutic combinations. During the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2023 Annual Meeting and the International Oncolytic Virus Conference in November 2023, Candel presented encouraging data on the discovery pipeline, demonstrating the effects of Alpha 201-macro-1, an investigational locally delivered biological oncolytic therapeutic designed to interfere with the CD47/SIRP1a pathway, in a mouse model of breast cancer.

About CAN-3110

CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation in a single therapeutic. Its activity is conditional to the expression of Nestin in cancer cells. CAN-3110 is being evaluated in a phase 1 investigator-sponsored clinical trial in patients with recurrent HGG. Earlier this month, the Company announced that Nature published results from this clinical trial. CAN-3110 was well tolerated with no dose-limiting toxicity reported and CAN-3110 plus prodrug was associated with improved survival. Positive HSV-1 serology was a predictor of response and was associated with improved survival. Increased infiltrating immune cells in the tumor microenvironment and expansion of the T cell repertoire after treatment were also associated with improved survival. In the clinical trial, the investigators observed a nearly doubling of the expected median overall survival after a single CAN-3110 injection, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. By comparison, survival in the anti-HSV1 positive patients treated with CAN-3110 was over 14 months. The Company and academic collaborators are currently evaluating the effects of multiple CAN-3110 injections in recurrent HGG, supported by the Break Through Cancer foundation, and expect initial results in H2 2024.

Candel will also initiate IND-enabling work in a second indication characterized by Nestin expression.

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, more than 950 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in NSCLC, borderline resectable pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials.

On November 28, 2023 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported that updated clinical trial data for vepdegestrant (ARV-471) will be presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) (Press release, Arvinas, NOV 28, 2023, View Source [SID1234638016]). Vepdegestrant is a novel oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader currently being investigated for the potential treatment of patients with locally advanced or metastatic estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Arvinas and Pfizer are collaborating to develop and commercialize vepdegestrant.

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!

Data from the Phase 1b study assessing vepdegestrant in combination with palbociclib (IBRANCE) will be presented in a spotlight session on December 7, 2023. An update on the Phase 2 vepdegestrant monotherapy (VERITAC) study will be presented in a poster presentation alongside four other posters during the symposium held from December 5-9, 2023, in San Antonio, Texas.

Session details are as follows in chronological order. For more information, visit the official SABCS website here.

VERITAC-2 Trial in Progress

Poster Session 1 (ID: PO1-19-12)
Wednesday, December 6, 12:00-2:00 PM CT

VERITAC-2: a Phase 3 study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER–positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer

Mario Campone
VERITAC-3 Study Lead-in Trial in Progress

Poster Session 2 (ID: PO2-20-03)
Wednesday, December 6, 5:00-7:00 PM CT

VERITAC-3: A randomized Phase 3 study, with a lead-in, of first-line vepdegestrant + palbociclib vs letrozole + palbociclib in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer

Seth Wander
TACTIVE-U Trial in Progress

Poster Session 2 (ID: PO2-20-04)
Wednesday, December 6, 5:00-7:00 PM CT

TACTIVE-U: Phase 1b/2 umbrella study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, combined with other anticancer treatments in ER–positive advanced or metastatic breast cancer

Claudine Isaacs
Vepdegestrant Monotherapy (VERITAC) Update

Poster Session 3 (ID: PO3-05-08)
Thursday, December 7, 12:00-2:00 PM CT

Updated results from VERITAC evaluating vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in ER-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer

Sara Hurvitz
Vepdegestrant + Palbociclib Phase 1b

Spotlight Session: Novel nuclear receptor targeting therapies (ID: PS15-03)
Thursday, December 7, 5:30-6:30 PM CT

Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, plus palbociclib in ER-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer: phase 1b cohort

Erika Hamilton
Pharmacokinetic/Pharmacodynamic Modeling of Palbociclib

Poster Session 5 (ID: PO5-14-11)
Friday, December 8, 12:00-2:00 PM CT

Leveraging a pharmacokinetic/pharmacodynamic (PK/PD) model to guide dose optimization of palbociclib in combination with Vepdegestrant

Brian Jermain
About vepdegestrant (ARV-471)
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits. Ongoing and planned clinical trials will continue to monitor and evaluate the safety and anti-tumor activity of vepdegestrant.

On November 28, 2023 TOLREMO therapeutics AG (TOLREMO) reported that the first patient has been dosed in its first-in-human clinical trial evaluating the safety and tolerability, pharmacokinetics, and pharmacodynamics of its lead candidate, TT125-802, in patients across a range of solid tumor indications (Press release, TOLREMO, NOV 28, 2023, View Source [SID1234638014]). TT125-802 is an orally available small molecule CBP/p300 bromodomain inhibitor designed to prevent non-genetic cancer drug resistance and thereby improve the response rates and durability of targeted cancer treatments. In preclinical testing, the compound has demonstrated the ability to block critical transcriptional resistance pathways responsible for cancer’s earliest escape mechanisms to targeted therapies.

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!

"Initiating our Phase 1 clinical trial is an important corporate milestone for TOLREMO. With TT125-802, we are leveraging our scientific insights to develop an effective CBP/p300 inhibitor with the potential to prevent resistance mechanisms across a broad spectrum of current and future targeted cancer treatments," said Stefanie Flückiger-Mangual, PhD, Co-founder and Chief Executive Officer of TOLREMO. "We are deeply committed to overcoming transcriptionally mediated cancer drug resistance for patient benefit, and this trial marks the start of an exciting new phase for the company."

The Phase I dose-escalation study will enroll patients across a range of solid tumor indications. The primary objective will be a safety assessment of TT125-802 as a monotherapy. Secondary objectives include the analysis of the drug’s biological activity, pharmacokinetics, pharmacodynamics, and target engagement, as well as the identification of the recommended dosing regimen and potential biomarkers for future patient stratification. The trial will be conducted initially at clinical centers in Europe, with the potential to include sites in the U.S. through an open Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Stepwise, TOLREMO will advance TT125-802 into clinical testing in combination with targeted therapies, such as KRAS, EGFR or AR inhibitors, in specific advanced solid tumor indications.

"TOLREMO’s in-depth preclinical analyses have showcased potency, selectivity, and safety data that demonstrate that TT125-802 has a highly differentiated profile, providing the foundation for translating these findings into the clinical setting. By specifically inhibiting transcriptional resistance pathways to targeted treatments, TT125-802 has the potential to profoundly improve the response rate and durability of other therapeutic interventions," said Alessandra Cesano, MD, PhD, consulting Chief Medical Officer at TOLREMO therapeutics.

On November 28, 2023 Portage Biotech Inc. (NASDAQ: PRTG), a clinical-stage immuno-oncology company advancing novel multi-targeted therapies for use as monotherapy and in combination, reported financial results for the fiscal quarter ended September 30, 2023 (Press release, Portage Biotech, NOV 28, 2023, View Source [SID1234638012]).

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!

"The Company is focused on developing its two lead clinical programs and maximizing its resources given market conditions. We continue to build on the favorable interim data and early evidence of single agent activity from the Phase 1/2 trial of our lead program, PORT-2, presented at SITC (Free SITC Whitepaper) earlier this month and the near-term focus is defining the recommended Phase 2 dose," said Dr. Ian Walters, Chief Executive Officer, and Chairman of Portage Biotech. "We are also excited with the progress and investigator interest in our ADPORT-601 adaptive Phase 1a/1b trial for PORT-6 (A2A inhibitor) and PORT-7 (A2B inhibitor) in multiple solid tumors, which was presented at SITC (Free SITC Whitepaper) by Sumit K. Subudhi of the University of Texas MD Anderson Cancer Center. Clinical enrollment for PORT-6 is progressing well, we have completed dosing in the low dose cohort and are enrolling patients in the next dose cohort." continued Dr. Walters. "Accrual in the Phase 1 portion of the PORT-2 trial is expected to be completed in the first calendar quarter of 2024, and we expect to make clinical updates at ASCO (Free ASCO Whitepaper) and SITC (Free SITC Whitepaper) during 2024 on both programs".

Company Highlights

Presented updated data support the proof of concept of using an iNKT engager monotherapy (PORT-2) to induce immune response for patients with non-small cell lung cancer (NSCLC) and melanoma at SITC (Free SITC Whitepaper).
Presented trial in progress of ADPORT-601: the Adenosine 2A(A2A) and Adenosine 2B(A2B) trial for patients with solid tumors with high adenosine receptor expression which has attracted strong academic interest in the clinical design.
Portage completed a $6 million financing in October 2023 for continued clinical development, general corporate and working capital purposes.
Financial Results from Quarter Ended September 30, 2023

The Company incurred a net loss of approximately $5.2 million and total comprehensive loss of approximately $6.5 million during the three months ended September 30, 2023 (the "Fiscal 2024 Quarter"), compared to a net loss and total comprehensive loss of approximately $1.1 million during the three months ended June 30, 2022 (the "Fiscal 2023 Quarter"), an increase in net loss of $4.1 million and an increase in total comprehensive loss of $5.4 million from the Fiscal 2023 Quarter.

Operating expenses for the Fiscal 2024 Quarter, which include research and development ("R&D") costs and general and administrative ("G&A") expenses, were $5.9 million compared to $3.6 million in the Fiscal 2023 Quarter, an increase of $2.3 million, which is discussed more fully below.

R&D costs increased by approximately $2.7 million to approximately $4.2 million, or approximately 180%, for the Fiscal 2024 Quarter from approximately $1.5 million in the Fiscal 2023 Quarter. The increase was primarily attributable to an overall increase in clinical trial and manufacturing-related costs associated with the clinical trials for PORT-2 (iNKT) and the PORT-6 and PORT-7 (adenosine assets). These increases in R&D costs reflect the clinical activity and manufacturing-related costs related to developing the Company’s adenosine and iNKT development programs.

G&A expenses decreased by approximately $0.4 million to approximately $1.7 million, or approximately 19%, from approximately $2.1 million in the Fiscal 2023 Quarter, due to the decreases in D&O insurance premiums, non-cash share-based compensation, and decreases in consulting fees relating to the Tarus acquisition incurred in the Fiscal 2023 Quarter.

As of September 30, 2023, the Company had cash and cash equivalents of approximately $3.4 million, and total current liabilities of approximately $3.1 million. Giving effect to the completion of the recent $6 million equity financing in October 2023, which generated proceeds, net of offering expenses, of $5.3 million, the Company’s cash and cash equivalents as of September 30, 2023, was approximately $8.7 million.

On November 28, 2023 Peptomyc, a Spanish clinical stage biotech company spin-off of the Vall d’Hebron Institute of Oncology (VHIO) and the Catalan Institute of Research and Advanced Studies (ICREA) in Barcelona, reported that in November the first patient of its Phase Ib clinical trial was successfully treated with OMO-103 – the first direct pan-Myc inhibitor to have completed Phase I clinical trial last year – in combination with the standard of care (SoC) drugs gemcitabine and nab-paclitaxel (Press release, Peptomyc, NOV 28, 2023, View Source [SID1234638010]).

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!

This Phase Ib trial includes patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma (PDAC). 4 sites in Spain are currently recruiting: the Hospital Universitari Vall d’Hebrón in Barcelona, the Instituto Catalán de Oncología in Barcelona, the Hospital General Universitario Gregorio Marañón in Madrid and the Hospital Universitario Miguel Servet in Zaragoza. The objective of this study is to evaluate the safety and efficacy of OMO-103 in combination with SoC in first-line metastatic PDAC.

Peptomyc CMO Manuela Niewel said: "We are thrilled to see the first patient successfully treated in this trial and this represents a major milestone for the company and patients we hope to serve" and Peptomyc CEO Laura Soucek added: "I am proud of the work of our team and thankful for the support from clinicians and hospitals who have enabled this important milestone."