On January 13, 2025 GSK plc (LSE/NYSE: GSK) and IDRx, Inc. (IDRx) reported that they have entered into an agreement under which GSK will acquire IDRx, a Boston-based, clinical-stage biopharmaceutical company dedicated to developing precision therapeutics for the treatment of GIST (Press release, GlaxoSmithKline, JAN 13, 2025, View Source [SID1234649657]). Under the agreement, GSK will pay $1 billion upfront, with potential for an additional $150 million success-based regulatory approval milestone payment. The acquisition includes lead molecule, IDRX-42, a highly selective KIT TKI being developed as a first- and second-line therapy for the treatment of GIST.

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GIST typically presents in the GI tract with 80% of cases driven by mutations in the KIT gene that lead to the growth, proliferation, and survival of tumour cells (primary or activating mutations).1 90% of patients treated in the first-line develop new KIT mutations (secondary or resistance mutations) that typically lead to relapse with limited therapeutic options.2 Currently, there are no approved TKIs that inhibit the full spectrum of clinically relevant primary and secondary mutations in KIT.

IDRX-42 has demonstrated activity against all key primary and secondary KIT mutations, designed to improve outcomes for patients with GIST. This breadth of mutational coverage, in addition to high selectivity which could improve tolerability, provides potential for a best-in-class profile.

Luke Miels, Chief Commercial Officer, GSK, said: "IDRX-42 complements our growing portfolio in gastrointestinal cancers. This acquisition is consistent with our approach of acquiring assets that address validated targets and where there is clear unmet medical need, despite existing approved products."

Tony Wood, Chief Scientific Officer, GSK, said: "We are excited by the early data from IDRX-42 and its unique ability to target all clinically relevant KIT mutations present in GIST, a major gap in the current standard of care. We look forward to accelerating its development in 2025 to redefine treatment."

Updated clinical data from StrateGIST 1, an ongoing phase I/Ib trial of IDRX-42 in patients with advanced GIST, were presented in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting. These data show promising anti-tumour activity of IDRX-42 in patients with advanced GIST with a manageable safety profile. Across patients with second-line or greater GIST, and amongst all KIT mutation subsets, the objective response rate (ORR) by modified RECIST v1.1 in the total efficacy evaluable population was 29% (n=87), including one complete response (CR) and 24 partial responses (PRs). Amongst patients who have had one prior line of therapy, the ORR was 53% (n=15) including one CR and 7 PRs.3

Across all patients, two of the PRs were awaiting confirmation at the time of the data cut, both of which were subsequently confirmed. The emerging durability data from StrateGIST 1 was also favourable. IDRX-42 was generally well-tolerated and treatment-related adverse events (TRAEs) were mainly low grade at the recommended phase Ib dose.4

Tim Clackson, CEO, IDRx, said: "We are looking forward to working with GSK to advance IDRX-42 for patients with GIST given there have been no major advances to the standard of care for almost 20 years. Combining our experience to date with GSK’s expertise in GI cancers, global clinical development capability, and strong commercial presence in oncology will help to accelerate the development of this novel medicine for patients."

GSK has a growing portfolio in development targeting the significant medical need in GI cancers, including ongoing trials with dostarlimab and GSK5764227 (GSK’227), a B7-H3-targeted antibody-drug conjugate. This agreement reflects GSK’s portfolio approach of identifying potentially best-in-class molecules with targeted mechanisms of action. The transaction supports GSK’s ambitions for growth through 2031 and beyond.

Financial considerations
Under the terms of the agreement, GSK will acquire one hundred percent (100%) of the outstanding equity interests (including all options and other incentive equity) in IDRx for up to $1.15 billion of total cash consideration, comprising an upfront payment of $1 billion with potential for an additional $150 million success-based regulatory approval milestone payment. GSK will also be responsible for success-based milestone payments as well as tiered royalties for IDRX-42 owed to Merck KGaA, Darmstadt, Germany.

This transaction is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.

For IDRx, Centerview Partners LLC is acting as exclusive financial advisor and Goodwin Procter LLP as legal counsel. For GSK, Leerink Partners LLC is acting as the exclusive financial advisor.

About GIST
Gastrointestinal stromal tumours (GIST) are the most common subtype of soft tissue sarcoma, with about 80,000 to 120,000 patients diagnosed with GIST per year worldwide.5 GIST typically presents in the GI tract with 80% of cases driven by mutations in the KIT gene that lead to the growth, proliferation, and survival of tumour cells (primary or activating mutations in exons 9 and 11).6 Additionally, about 90% of patients treated in the first-line develop new KIT mutations (secondary or resistance mutations in exons 13 and 17) that typically lead to relapse with limited therapeutic options.7 There are no approved TKIs that inhibit the full spectrum of clinically relevant primary and secondary mutations in KIT.

About IDRX-42
IDRX-42 is a highly selective, investigational small molecule tyrosine kinase inhibitor (TKI) designed to target all key KIT mutations in GIST. The U.S. Food and Drug Administration (FDA) has granted IDRX-42 Fast Track designation for the treatment of patients with GIST after disease progression on or intolerance to imatinib, and Orphan Drug designations for the treatment of GIST.

On January 13, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive results from the Phase 3 C-POST trial, which demonstrated that adjuvant treatment with PD-1 inhibitor Libtayo (cemiplimab) led to a statistically significant and clinically meaningful improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery (Press release, Regeneron, JAN 13, 2025, View Source [SID1234649673]).

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"While surgery is curative for most people living with cutaneous squamous cell carcinoma, many are burdened with a higher risk of recurrence that can lead to death or disfiguration," said Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial. "At the first prespecified interim analysis, Libtayo achieved a remarkably high bar in improving disease-free survival in high-risk cutaneous squamous cell carcinoma. With no currently approved options in the adjuvant setting, these landmark results demonstrate Libtayo could represent a major advance in delaying recurrence in these vulnerable patients."

C-POST enrolled 415 patients with high-risk CSCC who were randomized to receive either Libtayo or placebo for up to 48 weeks. The primary endpoint was DFS, defined as time from randomization to the first documented disease recurrence or death due to any cause. At the first prespecified interim analysis for DFS with a median duration of follow-up of 24 months (range: 2-64 months), Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, compared to placebo (hazard ratio: 0.32; 95% confidence interval: 0.20-0.51; p<0.0001).

Safety was assessed in 205 patients in the Libtayo arm and 204 patients in the placebo arm. Adverse events (AEs) of any grade occurred in 91% and 89% of patients in the Libtayo arm and the placebo arm, respectively. Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. Treatment discontinuations due to adverse reactions occurred in 10% and 1.5% of patients in the Libtayo arm and the placebo arm, respectively. Two patients experienced an AE leading to death in each arm.

Following these interim results, C-POST will continue for additional follow-up, including an analysis of the key secondary endpoint of overall survival. Detailed results will be presented at an upcoming medical meeting and will be shared with regulatory authorities with a plan for U.S. Food and Drug Administration (FDA) submission in the first half of 2025.

"Regeneron has long been a pioneer in non-melanoma skin cancer research. Libtayo was the first PD-1 inhibitor approved for certain patients with advanced cutaneous squamous cell carcinoma and has become a standard of care in this setting," said Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology, at Regeneron. "With these results, Libtayo now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma with adjuvant treatment. This trial is a testament to our unrelenting commitment to investigating areas where patient need remains high and to pursuing clinical research across diverse stages of skin cancer."

The potential use of Libtayo described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

About the Phase 3 Trial
C-POST is an ongoing randomized, placebo-controlled, double-blind, multicenter, global Phase 3 trial investigating Libtayo versus placebo as adjuvant treatment for patients with features associated with a high-risk of CSCC recurrence and who have completed surgery and post-operative radiation therapy. Trial participants are at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).

For the first 12 weeks, Libtayo 350 mg or placebo is administered intravenously every three weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks. The primary endpoint is DFS, and the secondary endpoints include freedom from locoregional recurrence, freedom from distant recurrence, overall survival, cumulative incidence of second primary CSCC tumors, and safety.

The Trans-Tasman Radiation Oncology Group (TROG), with Dr. Rischin as lead investigator, collaborated with Regeneron on protocol development. Trial sites included 24 TROG sites in Australia.

On January 13, 2025 AbCellera (Nasdaq: ABCL) reported that it has expanded its existing collaboration with AbbVie Inc. (NYSE: ABBV) to include the discovery of T-cell engagers (TCE) in oncology (Press release, AbCellera, JAN 13, 2025, View Source [SID1234649689]). The expansion builds upon the successful partnership established in December 2022 and includes access to AbCellera’s TCE platform to develop therapeutic antibodies for tumor targets.

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"We are pleased to broaden our AbbVie collaboration and look forward to using AbCellera’s TCE platform to bring novel cancer immunotherapies to patients in need," said Carl Hansen, Ph.D., founder and CEO of AbCellera.

Under the terms of the agreement, AbCellera will lead discovery activities and AbbVie has the right to develop and commercialize therapeutic antibodies resulting from the collaboration. AbCellera will receive upfront and research payments and is eligible to receive downstream milestone payments as well as tiered royalty payments on net sales.

On January 13, 2025 BridgeBio Pharma, Inc. (Nasdaq: BBIO) ("BridgeBio" or the "Company"), a new type of biopharmaceutical company focused on genetic diseases, reported updates on its commercial progress for Attruby (acoramidis), status of late-stage pipeline programs, and anticipated 2025 milestones (Press release, BridgeBio, JAN 13, 2025, View Source [SID1234649722]).

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"With the FDA’s approval of Attruby, we marked an important moment for both our organization and the broader ATTR-CM patient community in need of new treatment options. We’re grateful for the enthusiasm surrounding the product and the associated initial commercial momentum, with 430 prescriptions written by 248 unique physicians, and we look forward to continued progress," said Neil Kumar, Ph.D., Founder and CEO of BridgeBio. "Additionally, we are excited to share that we have completed enrollment of all three of our major market Phase 3 clinical trials. I look forward to continuing to work with this stellar team to serve patients with genetic disease in 2025."

Business Update
On November 22, 2024, the U.S. Food and Drug Administration (FDA) approved Attruby (acoramidis), a near-complete TTR stabilizer (≥90%), to reduce cardiovascular death and cardiovascular-related hospitalization in adult patients with ATTR-CM, a progressive fatal disease presenting as an infiltrative, restrictive cardiomyopathy resulting in heart failure.

Since the approval, BridgeBio has seen remarkable momentum with 430 patient prescriptions written by 248 physicians.

Pipeline Updates

BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9):

FORTIFY is a Phase 3 clinical trial of BBP-418 in LGMD2I/R9, a rare genetic disorder caused by variants in the fukutin‑related protein (FKRP) gene that result in progressive muscle degeneration and damage, and eventual loss of functional independence. The trial is fully enrolled with 112 patients.
The Company expects Last Patient – Last Visit (LPLV) and topline readout of the interim analysis cohort in second half 2025.
If successful, BBP-418 would be the first approved therapy for individuals living with LGMD2I/R9.

Encaleret – Calcium-sensing receptor (CaSR) antagonist for autosomal dominant hypocalcemia type 1 (ADH1):

CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1, a rare, genetic form of hypoparathyroidism, is fully enrolled with 70 patients. The trial is designed to evaluate the efficacy and safety of encaleret compared to standard of care in adult patients with ADH1.
The Company expects Last Patient – Last Visit and topline readout in second half 2025.
If successful, encaleret would be the first approved therapy for individuals living with ADH1.

Infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia:

PROPEL 3, the Phase 3 clinical trial of infigratinib in achondroplasia, the most common form of disproportionate short stature, is fully enrolled with 114 participants.
The Company expects Last Participant – Last Visit in second half 2025.
If successful, infigratinib would be the first approved oral therapy for children living with achondroplasia.

2025 Milestones

Program Status Anticipated 2025 Milestone
Acoramidis for ATTR-CM US FDA approval on November 22, 2024 EU and Japan approvals in 1H 2025
BBP-418 for LGMD2I/R9 FORTIFY, Phase 3 study enrollment completed Last Patient – Last Visit and Topline readout in 2H 2025
Encaleret for ADH1 CALIBRATE, Phase 3 study enrollment completed Last Patient – Last Visit and Topline readout in 2H 2025
Infigratinib for achondroplasia PROPEL 3, Phase 3 study enrollment completed Last Participant – Last Visit in 2H 2025

About Attruby (acoramidis)

INDICATION
Attruby is a transthyretin stabilizer indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization.

On January 13, 2025 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 recent successes across the Company’s viral immunotherapy portfolio and provided an update on the Company’s cash position and upcoming 2025 milestones (Press release, Candel Therapeutics, JAN 13, 2025, View Source [SID1234649642]).

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"I am incredibly proud of the Candel team for their successful execution of our 2024 priorities," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "We demonstrated substantial clinical activity for our investigational medicines and delivered strong results across our pipeline, including positive and pivotal topline phase 3 data for CAN-2409 in intermediate-to-high risk localized prostate cancer, positive topline overall survival data from the phase 2a randomized controlled clinical trial of CAN-2409 in borderline resectable PDAC, as well as topline overall survival data from the open label phase 2a clinical trial of CAN-2409 in patients with stage III/IV NSCLC. We have also reported initial clinical and biomarker activity after repeated injection of CAN-3110 in the ongoing phase 1b clinical trial in rHGG and encouraging data demonstrating CAN-3110’s potential in a second indication, in a model of melanoma. In 2024, we also presented data on two novel experimental assets generated using Candel’s enLIGHTEN Discovery Platform. During the 2024 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, we reported preclinical data for the first-in-class, tertiary lymphoid structure (TLS) inducer viral immunotherapy, and during the 2024 International Oncolytic Virotherapy Conference (IOVC), we presented data on a multimodal immunotherapy that delivers interleukin-12 (IL-12) and interleukin-15 (IL-15) to the tumor microenvironment."

Dr. Tak continued, "We are entering 2025 with clear momentum. Our primary focus will be achieving BLA readiness for CAN-2409 in prostate cancer. If approved, we believe that CAN-2409 has the potential to become a first-line treatment, as an addition to radiation therapy to reduce the risk of recurrence of prostate cancer, and to redefine the current standard-of-care for prostate cancer patients. In the upcoming months we look forward to collaborating closely with the FDA to ensure alignment in preparation for our BLA submission which, if approved, would enable us to deliver this much-needed therapy to patients."

2024 Accomplishments

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CAN-2409 – Prostate Cancer
•
In December, the Company reported positive topline data from its multicenter phase 3 clinical trial evaluating CAN-2409 in intermediate-to-high-risk localized prostate cancer patients. The study met its primary endpoint by demonstrating statistically significant improvement in disease-free survival (DFS) in patients who received CAN-2409 plus valacyclovir (prodrug) combined with standard of care (SoC) external beam radiation therapy (n=496) compared to standard of care alone (n=249) in the intent to treat population.
•
The data showed a 30% reduction in the risk for prostate cancer recurrence or death due to any cause for the CAN-2409 treatment arm compared to placebo control arm (p=0.0155), and 80.4% pathological complete responses in 2-year post-treatment biopsies after CAN-2409 administration compared to 63.6% in the control arm (p=0.0015). The safety profile of CAN-2409 was generally consistent with previous studies, with no new safety signals identified.
•
This study was conducted under a Special Protocol Assessment (SPA) with U.S. Food and Drug Administration (FDA) agreement on key aspects of study design, meaning that safety and efficacy data generated from the study could be sufficient for the Company to seek regulatory approval for CAN-2409 in this indication.

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FDA previously granted Fast Track Designation for CAN-2409 for the treatment of prostate cancer.
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CAN-2409 – Pancreatic Cancer
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In April 2024, the Company announced positive updated survival data, from the phase 2a randomized controlled clinical trial of CAN-2409 plus valacyclovir (prodrug), together with SoC chemoradiation, in borderline resectable PDAC (n=13). The data showed notable improvements in estimated median overall survival (mOS) of 28.8 months after experimental treatment with CAN-2409 versus 12.5 months in control group. At 24 months, the survival rate was 71.4% in CAN-2409-treated patients versus 16.7% in the control group. At 36 months, estimated survival was 47.6% in the CAN-2409 group versus 16.7% in the control group.
•
FDA previously granted Fast Track Designation for CAN-2409 in borderline resectable PDAC.
•
FDA granted Orphan Drug Designation for CAN-2409 in borderline resectable PDAC in April 2024.
•
CAN-2409 – Non-Small Cell Lung Cancer
•
At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the Company presented topline overall survival data from the phase 2a clinical trial of CAN-2409 plus valacyclovir in combination with continued immune checkpoint inhibitor (ICI) therapy in patients with stage III/IV NSCLC inadequately responding to ICI therapy. The data (as of April 1, 2024) showed mOS of 20.6 months in patients with progressive disease (n=41) despite ICI treatment compared to published results of less than 12 months with SoC docetaxel-based chemotherapy in similar patient populations.
•
As of the data cut-off date, CAN-2409 treatment in NSCLC continued to exhibit a favorable safety and tolerability profile.
•
FDA previously granted Fast Track Designation for CAN-2409 for the treatment of NSCLC.
•
CAN-3110 – Recurrent High-Grade Glioma
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Presented a Trial-in-Progress poster at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting on the ongoing phase 1b clinical trial exploring multiple doses of CAN-3110 in patients with rHGG.
•
Presented updated clinical and biomarker activity data at the IOVC in October 2024. Investigators reported ongoing improved survival compared to historical controls, with 3 out of 6 patients still alive after more than one year (12.2, 13.0, and 18.7 months, respectively) after initiation of experimental treatment with repeated CAN-3110 injections
•
FDA granted Orphan Drug Designation for CAN-3110 for treatment of rHGG in May 2024.
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FDA granted Fast Track Designation for CAN-3110 for the treatment of rHGG in February 2024.
•
CAN-3110 – Melanoma
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Presented preclinical results on the therapeutic potential of CAN-3110 in the Ras-Raf pathway altered melanoma model at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting. CAN-3110 exhibited potent, tumor-specific cytotoxicity in human and murine melanoma cell lines with varied CDKN2A pathway alterations and Nestin expression. In vivo mouse studies showed dose-dependent inhibition of tumor growth, with regression observed in a subset (3 of 8) of tumors treated with a high dose of CAN-3110. The therapy was well-tolerated in preclinical mouse models based on body weight and histopathological analysis following intra-tumoral administration.
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enLIGHTEN Discovery Platform
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Presented data on a new multimodal viral therapeutic candidate encoding IL-12 and IL-15 at the 2024 IOVC. Data showed the ability of the asset to induce expansion and activation of natural killer and CD8+ T cell populations, resulting in significant tumor growth inhibition and tumor regression in two different models.
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Presented data at the AACR (Free AACR Whitepaper) 2024 Annual Meeting describing a first-in-class, multimodal immunotherapy candidate for the induction of tertiary lymphoid structures, being developed as a novel therapeutic strategy for solid tumors. Delivery of two unique payload combinations, predicted in silico using the enLIGHTEN Advanced Analytics suite, was shown to induce TLS formation, inhibit tumor growth, and improve response to ICI therapy in preclinical models of cancer.
2025 Anticipated Milestones and Key Catalysts

•
CAN-2409 – Pancreatic Cancer
•
Updated overall survival data from phase 2a clinical trial, expected in Q1 2025
•
Preparations underway for potential phase 2b, randomized clinical trial
•
CAN-2409 – Non-Small Cell Lung Cancer
•
Updated overall survival data from phase 2a clinical trial, expected in Q1 2025

•
Preparations underway for potential phase 2b, randomized clinical trial
•
CAN-2409 – Prostate Cancer
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Presentation of the phase 3 clinical trial data at upcoming scientific conference
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Publication of the phase 3 clinical trial data in a scientific journal
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BLA submission on track for Q4 2026
•
CAN-3110 – Recurrent High-Grade Glioma
•
Overall survival data from ongoing phase 1b clinical trial evaluating multiple doses, expected in Q4 2025

Cash Position

Cash and cash equivalents, as of December 31, 2024, were $102.9 million (unaudited), as compared to $35.4 million (audited) as of December 31, 2023. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will support the preparation and submission of a BLA for CAN-2409 in prostate cancer, as well as fund its current operating plan into Q1 2027.

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 tumor. 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. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.

Currently, Candel is evaluating CAN-2409 in NSCLC, and borderline resectable PDAC, in ongoing clinical trials, and has recently completed phase 2b and phase 3 clinical trials in localized, non-metastatic prostate cancer. CAN-2409 plus prodrug (valacyclovir) has been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy and localized primary prostate cancer. Candel’s pivotal phase 3 clinical trial in prostate cancer was conducted under a Special Protocol Assessment agreed with the FDA. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC.

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. CAN-3110 is being evaluated in a phase 1b clinical trial in patients with rHGG. In October 2023, the Company announced that Nature published results from this ongoing clinical trial. CAN-3110 was well tolerated with no dose-limiting toxicity reported. In the clinical trial, the investigators observed improved median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition.1 The Company and academic collaborators are currently evaluating the effects of multiple CAN-3110 injections in rHGG, supported by the Break Through Cancer foundation. CAN-3110 has previously received FDA Fast Track Designation and Orphan Drug Designation for the treatment of rHGG.

About the enLIGHTEN Discovery Platform

The 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. The enLIGHTEN Discovery Platform has been designed to deconvolute the characteristics of the tumor microenvironment related to clinical outcomes. These characteristics are rapidly translated into optimized multi-gene payloads of tumor modulators that can be delivered to the tumor microenvironment for specific indications, disease stages, and rationally designed therapeutic combinations. In 2022, the Company announced a discovery partnership with the University of Pennsylvania Center for Cellular Immunotherapies to create new viral immunotherapies that could enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy in solid tumors. During the SITC (Free SITC Whitepaper) 2023 Annual Meeting and the 2023 IOVC meeting, Candel presented encouraging data on the first candidate from this platform, Alpha 201-macro-1, which was designed to interfere with the CD47/SIRP1α pathway, in mouse models of breast cancer and lung cancer. During the AACR (Free AACR Whitepaper) Annual Meeting 2024, Candel presented preclinical data, unveiling the second candidate from the enLIGHTEN Discovery Platform, a first-in-class multimodal immunotherapy candidate to induce TLS, being developed as a novel therapeutic for solid tumors. Candel presented data at the 2024 IOVC meeting. The presentation focused on a multimodal viral therapeutic candidate encoding IL-12 and IL-15, the latest asset from the platform.