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CEL-SCI Reports Phase 3 Tumor PD-L1 Biomarker Data Demonstrate Multikine’s Increased Efficacy and Points to Potential for Combination With Checkpoint Inhibitors for Head & Neck Cancer

On July 11, 2023 CEL-SCI Corporation (NYSE American: CVM) reported new data from a biomarker analysis of its pivotal Phase 3 study in newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN) at the American Head and Neck Cancer Society’s (AHNS) 11th Annual International Conference on Head and Neck Cancer on July 10, 2023 in Montreal, Canada, in the presentation titled "Tumor cell PD-L1 biomarker confirms Leukocyte Interleukin Injection (LI) treatment (Tx) survival outcome advantage in naïve locally advanced primary head & neck squamous cell carcinoma (SCCHN), the IT-MATTERS Study" (Press release, Cel-Sci, JUL 11, 2023, View Source [SID1234633182]). The Leukocyte Interleukin Injection (LI) [aka Multikine*] talk, was delivered by Philip Lavin, PhD, lead biostatistician for over 80 regulatory approvals/clearances who has also served on multiple U.S. Food and Drug Administration (FDA) review panels. Dr. Lavin is the lead biostatistician for CEL-SCI’s IT-MATTERS study.

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Tumor cell PD-L1, also known as PD-L1 (Programmed Death-Ligand 1), a protein that plays a crucial role in immune system regulation, is a target pathway for immune checkpoint inhibitors, a major class of oncology drugs. These work by blocking the interaction between tumor cell PD-L1 and the PD-1 receptor. The global PD-L1/PD-1 therapeutics market was valued at $34.8 billion in 2022 and includes two drugs approved for head and neck cancer, specifically unresectable recurrent or metastatic SCCHN, Keytruda and Opdivo.

While pembrolizumab (Keytruda) and nivolumab (Opdivo) are approved for use in recurrent and metastatic head and neck cancer, CEL-SCI’s Phase 3 data showed that Multikine prolonged overall survival in the lower risk for recurrence advanced primary head and neck cancer patients and more so in a subset comprising >70% of the lower-risk patients (all had low levels (defined as TPS<10) of tumor cell PD-L1 expression).

"This data is of great interest in that, in our opinion, they suggest Multikine can be effective in extending life in patients who are generally not well served by checkpoint inhibitors. A combination of Multikine and drugs like Keytruda or Opdivo may in fact extend the reach of coverage in this hard-to-treat disease and thus help more patients, indicating a promising new treatment path," stated CEL-SCI CEO Geert Kersten. "Our immediate opportunity is in head and neck cancer, yet these latest results also point to potential in other solid tumors as well. We are interested in running such combination studies."

The AHNS presentation focused on biomarker analysis, specifically featuring tumor cell PD-L1, from tumor specimens that were collected from nearly half of the patients in CEL-SCI’s pivotal Phase 3 study.

In June of 2021, a Multikine study reported a statistically significant 14.1% absolute 5-year overall survival benefit in the intent to treat (ITT; n=923) subjects who were categorized as lower risk for recurrence (LR; n=380) per National Comprehensive Cancer Network (NCCN) guidelines and received Multikine followed by surgery and radiotherapy, as compared to control LR subjects who received only standard of care (SOC) (surgery plus radiotherapy), resulting in a near 4-year median overall survival advantage over control (101.7 vs 55.2 months). The Company is pursuing paths to marketing approval for Multikine in the treatment of head and neck cancer in the USA, Canada, the UK and the European Union.

Highlights of the data we presented at AHNS conference include:

A Kaplan-Meier lifetable for low tumor cell PD-L1 (defined as TPS <10) demonstrated a significant log rank test (2-sided p=0.034) favoring the Multikine plus Standard of care (SOC) group vs SOC alone; there was an absolute 20% survival advantage at 5-year favoring both Multikine plus SOC (~60% alive) vs SOC alone (~40% alive)
The PD-L1 low subgroup represents >70% of all LR subjects
Two-way and three-way interaction models for the LR population confirmed statistical significance favoring Multikine treatment regimen plus SOC vs SOC alone with a 0.6 hazard ratio for 3-way interaction and a 0.55 hazard ratio for the 2-way interaction vs 0.68 hazard ratio for the study LR population that contained all patients, not just those with low PD-L1 (TPS <10)
The data suggest potential benefits for combining Multikine with checkpoint inhibitors to further improve overall survival outcome in this hard-to-treat patient population.

Fully recruited EPIC-Skin international study for the treatment of Non-Melanoma Skin Cancer

On July 11, 2023 OncoBeta GmbH, a medical device company specialised in innovative epidermal radioisotope therapies, reported that the phase IV international multi-centre study designed to further evaluate the Complete Response Rate of patients with non-melanoma skin cancer after treatment with Rhenium-SCT is now fully recruited (Press release, OncoBeta, JUL 11, 2023, View Source [SID1234633181]).

The EPIC-Skin study (Efficacy of Personalised Irradiation with Rhenium-SCT for the treatment of non-melanoma skin cancer) is based on the proven effect of the ß-emitter rhenium-188 in the treatment of basal cell (BCC) and squamous cell carcinomas (SCC)1,2. The study aims to further evaluate the efficacy of Rhenium-SCT as well as important Patient Reported Outcome Measures such as quality of life, treatment comfort and cosmetic outcomes.

Patients treated had a confirmed histopathology of stage I or II non-melanoma skin cancer. With the latest treatment round complete, all patients are now in the follow-up phase, which monitors quality of life, treatment comfort and cosmetic outcomes over the next 24 months. An interim analysis is expected to be published in mid 2023.

Professor Mike Sathekge, an internationally acclaimed researcher and current Head of Nuclear Medicine at Steve Biko Academic Hospital in Pretoria, South Africa, treated his first patient enrolled in EPIC-Skin in November 2022, and the latest patient marks the final treatment in the study.

An international multi-centre trial, the EPIC-Skin study is being conducted across five countries and seven major cities including Rostock, Vienna, London, Pretroria, Gold Coast, Perth and Sydney with more than 180 patients taking part.

There are more than 7.7 million cases of NMSC each year, and incidence rates are increasing globally.3,4 Traditional treatments for NMSCs predominantly involve surgery, which carries a risk of scarring or loss of function. Treatment with Rhenium-SCT employs a non-invasive superficial application of a paste containing ß-emitting particles directly to the lesion, which eliminate cancer cells without the need for surgery.2,5,6

Dr. Gerhard Dahlhoff, Medical Director at OncoBeta GmbH, stated: "We are excited to complete the final patient recruitment within EPIC-Skin as we will now start to receive data on the quality-of-life outcomes. With patients in study centres across Australia, Austria, Germany, United Kingdom and South Africa, we have a mix of patients, ethnicities, NMSC localisations and lesion characteristics which will enable us to even further evaluate the outcomes of treatment with Rhenium-SCT."

Shannon D. Brown III, CEO and Managing Director at OncoBeta GmbH, said, "The patient journey is often a difficult one, so it is critical that the medical community continues to improve and develop new treatment options for patients with NMSCs. The EPIC-Skin clinical study has the potential to influence and change the way we evaluate and fit NMSC treatments to the individual needs and requirements of patients."

ClinicalTrials.gov Identifier: NCT05135052

About the Rhenium-SCT (Skin Cancer Therapy)
Non-melanoma skin cancer (NMSC) is the most common form of cancer in humans.4 The most common cause of NMSC is sun exposure, while other predisposing factors include genetic skin conditions and immunosuppressive diseases or treatments.7

The Rhenium-SCT is a painless*, single session†, non-invasive‡ therapy that provides aesthetic results, even in cases otherwise considered difficult to treat.2,5,6 The Rhenium-SCT utilizes the radioisotope Rhenium-188 in an epidermal application with optimal properties for the treatment of NMSCs (non-melanoma skin cancers). The Rhenium-SCT is a precise, personalised1,2 therapy that is only applied to the area needed to treat without affecting the healthy tissue. The specially designed device ensures the Rhenium-SCT compound never comes in direct contact with the patient’s skin and the application is safe and simple for the applying physician. Most cases of NMSCs (Basal Cell Carcinomas and Squamous Cell Carcinomas) can be treated using the Rhenium-SCT in one single session.2,5,6† Scar-free healing of the treated lesion area and the regeneration of healthy tissue occurs usually within a few weeks after treatment.

Ratio Therapeutics, In Collaboration with Lantheus and PharmaLogic, Announce First Patient Dosed in Phase I Study Evaluating a Novel FAP-Targeted Radiopharmaceutical for PET Imaging

On July 11, 2023 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company that employs a suite of innovative technologies to develop best-in-class radiopharmaceuticals for the monitoring and treatment of cancers reported that in partnership with Lantheus, a company committed to improving patient outcomes through diagnostics, radiotherapeutics and artificial intelligence solutions that enable clinicians to Find, Fight and Follow disease, and in collaboration with PharmaLogic, a world-class contract development and manufacturing organization (CDMO) specializing in radiopharmaceuticals, that it has initiated dosing in a Phase I study evaluating the pharmacokinetics, biodistribution and radiation dosimetry of a novel fibroblast activation protein-alpha (FAP)-targeted radiopharmaceutical, Copper-64[Cu-64]-labeled RTX-1363S, for PET imaging in adult healthy volunteers (Press release, Ratio Therapeutics, JUL 11, 2023, View Source [SID1234633180]).

FAP is a membrane-bound dipeptidyl peptidase that is specifically expressed in activated fibroblasts. The ubiquitous expression of FAP in cancer-associated fibroblasts across nearly all epithelial-derived cancers paired with the low abundance in normal tissues, makes it a unique target to exploit for tumor imaging for a wide variety of cancers such as breast, pancreatic, lung and stomach cancer.

"Today marks a major milestone for Ratio as we take a crucial step forward in the development of our FAP-targeted imaging agent," said Dr. John Babich, Ratio’s President and Chief Scientific Officer. "Cancer-associated fibroblasts selectively expressing FAP comprise up to 90% of the tumor mass in highly desmoplastic cancers, including pancreatic, breast, and colorectal. RTX-1363S has the potential to transform the way we detect and monitor various epithelial-derived cancers."

"We are delighted by our collaboration with Ratio Therapeutics in advancing the clinical development of RTX-1363S as a FAP-targeted diagnostic to the clinic," stated Etienne Montagut, Lantheus’ Chief Business Officer. "By leveraging our expertise in radiopharmaceuticals, we aim to contribute to the early detection and accurate monitoring of epithelial-derived cancers. This partnership exemplifies our commitment to Find, Fight and Follow disease by delivering innovative solutions to improve cancer care, ultimately leading to better patient outcomes."

"PharmaLogic is honored to contribute its manufacturing expertise in radiopharmaceuticals to this clinical trial, advancing diagnostics for epithelial-derived cancers," said Scott Holbrook, Chief Strategy Officer, General Manager PET & Precision Medicine at PharmaLogic, the manufacturing partner involved in the trial. "This further strengthens our commitment to production and development of novel radiopharmaceuticals to advance cancer treatments and quality of life for cancer patients."

Ratio’s clinical candidate, RTX-1363S, is a highly selective, high affinity FAP inhibitor that will be radiolabeled with copper-64 (Cu-64), a positron-emitting radionuclide with a half-life of 12.7 hr. In the first study, biodistribution and pharmacokinetics will be evaluated following a single injection of [Cu-64]-labeled RTX-1363S in a small subset of adult healthy volunteers. Study subjects will be screened within 28 days of administration and up to 6 eligible subjects will be enrolled, including 3 female and 3 male subjects. Results from the study will inform further development of [Cu-64]-labeled RTX-1363S as a FAP-targeted tumor imaging agent.

About Trillium and Macropa
Ratio Therapeutics’ fully integrated proprietary R&D platforms, Trillium and Macropa, harness the tumor-killing power of alpha particles. The tunable nature of the platforms enables the efficient and timely development of numerous novel radiopharmaceuticals for a broad range of high unmet need in solid tumors, while addressing the trifecta of typical challenges seen with most radiopharmaceuticals: delivery, safety and efficacy. Trillium is a pharmacokinetic modulation platform that can be altered to bind to any antigen-specific target, while Macropa is a best-in-class Actinium-225 chelator. The combination of these platforms enables the tumor-killing power of alpha particles with potential for first- and best-in-class radiopharmaceuticals.

TRACON Pharmaceuticals Announces Collection of Arbitration Award from I-Mab Biopharma

On July 11, 2023 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported that it has collected the previously announced arbitration award from I-Mab Biopharma (Press release, Tracon Pharmaceuticals, JUL 11, 2023, View Source [SID1234633175]).

"We are pleased to collect the award. As we previously announced in April, the net proceeds extend our cash runway into early 2024 and past expected full accrual of the ENVASARC pivotal trial," said Charles Theuer, M.D., Ph.D., TRACON’s Chief Executive Officer. "We look forward to reporting the interim efficacy assessment from ENVASARC in the third quarter of 2023, which includes a futility analysis that we have already met based on responses seen to date."

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines. TRACON has received orphan drug designation from the U.S. Food and Drug Administration for envafolimab for patients with soft tissue sarcoma and fast track designation from the U.S. Food and Drug Administration for envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. ENVASARC is enrolling patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor. A total of 80 patients will receive treatment with single agent envafolimab at 600 mg every three weeks. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint.

Silence Therapeutics Achieves $4 Million in Research Milestone Payments from Hansoh Pharma Collaboration

On July 11, 2023 Silence Therapeutics plc, Nasdaq: SLN ("Silence" or "the Company"), an experienced and innovative biotechnology company committed to transforming peoples’ lives by silencing diseases through precision engineered medicines, reported that it will receive a $4.0 million cash payment from Hansoh Pharmaceutical Group Company Limited ("Hansoh") following the achievement of two undisclosed preclinical milestones (Press release, Silence Therapeutics, JUL 11, 2023, View Source [SID1234633174]).

"We are very pleased with the continued progress being made in our Hansoh Pharma collaboration," said Craig Tooman, President and CEO of Silence. "Today’s news follows the $10.0 million milestone payment we achieved in our AstraZeneca collaboration in May and reflects our ongoing efforts to advance our partnered pipeline. We continue to be excited about the advancement of our siRNA technology in both partnered and proprietary programs."

Silence and Hansoh entered a collaboration in October 2021 to develop siRNAs ("short interfering RNAs") leveraging Silence’s proprietary mRNAi GOLD platform for three undisclosed targets. Under the terms of the agreement, Silence has exclusive rights to the first two targets in all territories except the China region. Hansoh has the exclusive option to license rights to those two targets in Greater China, Hong Kong, Macau and Taiwan, and global rights to the third target.

Hansoh made a $16 million upfront payment to Silence and the Company is eligible to receive up to $1.3 billion in development, regulatory and commercial milestones. Silence is also eligible to receive royalties tiered from low double-digit to mid-teens on Hansoh net product sales. Today’s announcement represents the second and third research milestone payments achieved under the collaboration. The Company achieved the first milestone payment for $2.0 million in April 2022.