On December 14, 2023 Nerviano Medical Sciences S.r.l. (NMS), a clinical-stage biotechnology company member of NMS group, reported the signing of a license agreement with Italfarmaco S.p.A. (ITF), a specialty pharmaceutical company, to develop and commercialize a novel peptide-drug conjugate (PDC) (Press release, Nerviano Medical Sciences, DEC 14, 2023, View Source [SID1234638569]).

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Under the terms of the agreement, ITF will use NMS’s proprietary linker-payload technology to develop a novel PDC product candidate. NMS has implemented linker-payload GMP manufacturing and supply at a CDMO referred by NMS. ITF will be responsible for generating the target peptide and all non-clinical, clinical, and commercialization activities related to any resulting proprietary product candidates. Financial details of the agreement have not been disclosed.

"NMS’s cutting-edge linker-payload technology will allow us to develop new peptide drug conjugates for the treatment of oncology indications with high unmet medical need, leveraging Italfarmaco’s state-of-the-art GMP peptide production capabilities," stated Christian Steinkühler, PhD, Italfarmaco Group’s Chief Scientific Officer. "This is an important milestone in our mission to generate a highly diversified pipeline of innovative medicines."

"We are pleased that ITF, a company with a long-standing heritage both from pharmaceutical and chemical sectors, has selected our linker-payload first platform for developing a truly novel peptide-drug conjugate. This is a significant step to broaden the applicability of our technology," said Hugues Dolgos, PharmD, Chief Executive Officer of NMS and NMS Group.

On December 14, 2023 Kiromic BioPharma, Inc. (OTCQB: KRBP) ("Kiromic" or the "Company"), a clinical-stage, fully-integrated biotherapeutics company using its proprietary DIAMOND artificial intelligence and data mining platform to develop cell therapies with a focus on immuno-oncology, reported that the first patient has initiated treatment at the Beverly Hills Cancer Center (BHCC) in the Company’s Deltacel-01 clinical trial (Press release, Kiromic, DEC 14, 2023, View Source [SID1234638567]). This Phase 1 study is evaluating Deltacel for the treatment of stage 4 metastatic non-small cell lung cancer (NSCLC).

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Initial tolerability and safety data from this first patient is expected to be available by year-end. Additionally, Kiromic expects to report preliminary efficacy results from the first patient by the end of January 2024.

The Company expects that the Deltacel-01 clinical trial will start enrolling patients at two additional clinical sites in early 2024.

"We are extremely proud to initiate this first-in-human trial of Deltacel when we stated we would," said Pietro Bersani, Chief Executive Officer of Kiromic. "Non-small cell lung cancer represents a significant unmet medical need, and a leading cause of death in the U.S. We look forward to enrolling additional patients to advance the clinical development of Deltacel for the treatment of solid tumors, starting with NSCLC."

"Beverly Hills Cancer Center is pleased to announce the dosing of the first patient in our Deltacel-01 study," said Dr. Afshin Eli Gabayan, Medical Oncologist, Medical Director, and Principal Investigator at Beverly Hills Cancer Center. "We are excited about the potential of this novel Gamma Delta T-cell therapy combined with low dose radiation for our patients with lung cancer who have few treatment options left. We look forward to evaluating long term safety and efficacy outcomes as the study progresses."

Dr. Arash Gabayan, Radiation Oncologist at Beverly Hills Cancer Center and the sub-investigator who administered the low dose radiation treatments, commented: "The first course of combination of Deltacel and low dose radiation was successfully delivered to this first patient. Our clinical research team will continue monitoring this patient closely as we seek to understand how this innovative and exciting dual approach may impact the immune response against the cancer cells. We are hopeful that this investigational treatment approach can make a meaningful difference for lung cancer patients."

In Kiromic’s open-label Phase 1 clinical trial, titled "Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer" (NCT06069570), patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel with four courses of low-dose, localized radiation over a 10-day period. The primary objective of the study is to evaluate safety, while secondary ones include objective response, progression-free survival, overall survival, time to progression, time to treatment response, and disease control rates.

About Deltacel

Deltacel (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of non–small cell lung cancer. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel is Kiromic BioPharma’s leading candidate in its GDT platform. Deltacel is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial focus on NSCLC, the most prevalent type of lung cancer and representing about 80% to 85% of lung cancer cases. Data from two preclinical studies demonstrated Deltacel’s favorable safety and efficacy profile when it was combined with low-dose radiation.

On December 14, 2023 The European Organisation for Research and Treatment of Cancer (EORTC) reported the launch of EORTC 2120 RAVINA trial supported by the EORTC Head and Neck Cancer Group and by Merck entitled "Radiotherapy plus xevinapant or placebo in older patients with locally advanced head and neck squamous cell carcinoma: a randomized phase II study" (Press release, EORTC, DEC 14, 2023, View Source [SID1234638563]).

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This randomised, placebo-controlled, phase II study will determine the efficacy and safety of xevinapant with radiotherapy in older patients. Patients aged 70 years or older with LA-HNSCC of oral cavity, oropharynx, hypopharynx, or larynx for which treatment with radiotherapy only is recommended will be enrolled in the study.

This study aims to find out whether the addition of xevinapant increases response to radiotherapy, progression free survival and overall survival and may impact health-related quality of life, frailty and circulating markers.

Launch of the trial across Europe

Ten countries have been selected to participate in the trial (Italy, France, Belgium, Spain, Ireland, Germany, the Netherlands, Slovenia, Norway and the United Kingdom) with 27 sites expected to enrol approximately 230 patients.

Merck will provide xevinapant and the placebo. The study was submitted under the new EU Clinical Trial Regulation in March 2023. Today, 7 sites have been authorised in five countries. First Patient In has been enrolled in Belgium.

Xevinapant (formerly known as Debio 1143) is an investigational, orally taken Inhibitor of Apoptosis Protein (IAP) inhibitor that may promote cancer cell death via apoptosis. Xevinapant is believed to sensitize tumour cells for various cytotoxic therapies, including radiotherapy and chemotherapy.

Improving progression-free survival with limited toxicity in older patients

"Locally advanced head and neck cancer is a debilitating disease that is increasingly diagnosed in older patients. These patients often do not tolerate or benefit from addition of chemotherapy to radiotherapy and are therefore treated with radiotherapy alone. The disease relapses in more than half of the patients. An earlier study showed that xevinapant added to chemoradiotherapy reduced relapses and improved overall survival with limited extra toxicity. We therefore hypothesize that xevinapant will also improve efficacy of radiotherapy alone" said Dr. Sjoukje Oosting, Medical Oncologist at the University Medical Centre in Groningen, the Netherlands, lead investigator of the EORTC 2120 RAVINA study.

On December 14, 2023 – Bio-Path Holdings, Inc., (NASDAQ: BPTH) a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported completion of the first dose cohort of the dose escalation portion of its Phase 1/1b clinical trial of BP1002 evaluating the ability of BP1002 to treat refractory/relapsed acute myeloid leukemia (AML) patients including venetoclax-resistant patients (Press release, Bio-Path Holdings, DEC 14, 2023, View Source [SID1234638562]).

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"We are delighted to safely complete this first dose cohort and to advance BP1002 into the next cohort as it brings us one step closer to providing access to this very promising treatment for the most vulnerable patients who have limited therapeutic options," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "We look forward to advancing this study in higher doses with the hope that increased levels of BP1002 will prove even more efficacious and safe in these sickest of sick patients."

A total of three evaluable patients per dosing cohort are scheduled to be treated with BP1002 monotherapy in a standard 3+3 design, unless there is a dose limiting toxicity which would require an additional three patients tested. The first dose cohort consisted of a starting dose of 20 mg/m2, and there were no dose limiting toxicities. The approved treatment cycle is two doses per week over four weeks for a total of eight doses administered over twenty-eight days. The Phase 1b portion of the study is expected to commence after completion of BP1002 monotherapy cohorts and will assess the safety and efficacy of BP1002 in combination with decitabine in refractory/relapsed AML patients.

Gail J. Roboz, M.D., is the National Principal Investigator for the Phase 1/1b trial. Dr. Roboz is a professor of medicine and director of the Clinical and Translational Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York City. Gary Schiller, M.D., The University of California at Los Angeles Cancer Center, Maro Ohanian, D.O., Department of Leukemia, University of Texas MD Anderson Cancer Center, and David Hermel, M.D., Scripps Health, are each serving as principal investigators.

About BP1002

BP1002 targets the protein Bcl-2, which is responsible for driving cell survival in up to 60% of all cancers. The current standard of care for patients with AML not eligible for intensive chemotherapy is venetoclax, an oral Bcl-2 inhibitor that targets the BH3 domain of the Bcl2 protein, in combination with a hypomethylating agent or with low-dose cytarabine. Unfortunately, many patients become resistant to venetoclax treatment. A published study found that AML patients who had relapsed from frontline venetoclax-based treatment were refractory to salvage therapy and had a median survival of less than 3 months. By targeting Bcl-2 at the mRNA level rather than the protein, BP1002 may overcome and prevent some of the mechanisms of resistance that affect venetoclax treatment. Published preclinical studies have shown BP1002 to be a potent inhibitor against the Bcl-2 target and its benign safety pro�ile should enable effective BP1002 combination therapy with approved agents, such as decitabine.

On December 14, 2023 Bicycle Therapeutics (Nasdaq: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that it is hosting a Research & Development (R&D) Day for investors and analysts in New York to provide clinical updates for BT8009, BT7480 and BT5528, and an overview of the company’s strategy and pipeline opportunities (Press release, Bicycle Therapeutics, DEC 14, 2023, View Source [SID1234638561]). The company will also highlight the broad capabilities of its novel Bicycle platform technology. The event begins at 8 a.m. ET and will be available via webcast here.

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"During our first R&D Day, we are excited to showcase the advantages of our Nobel Prize-winning science and our strategy to discover and develop therapies with greater tolerability that could provide enhanced benefit to a multitude of patients, starting with those who have cancer," said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. "Through our Nectin-4 and EphA2 portfolios and the continued work on our platform, including through partnerships, we are building a leading precision-guided therapeutics company with the potential to address a wide range of diseases that affect millions of people around the world. We believe that our technology has the potential to not only help patients live longer but also to live well."

"Today we are excited to provide clinical updates for our three lead programs," said Santiago Arroyo, M.D., Ph.D., Chief Development Officer of Bicycle Therapeutics. "In totality, the data support the emerging differentiated profile of our Bicycle molecules, paving the way to deliver best-in-class or first-in-class therapies for many cancers. Based on our clinical updates, we are taking important next steps with our development programs, setting up what we expect to be a catalyst-rich 2024."

Key R&D Day Highlights

Nectin-4 Portfolio

Bicycle Therapeutics is advancing two clinical programs, BT8009 and BT7480, targeting Nectin-4, a well-validated tumor antigen with elevated levels of expression in multiple tumor types.

BT8009 is a Nectin-4 Bicycle toxin conjugate (BTC) designed to overcome the significant toxicity associated with other toxin conjugate approaches. In the ongoing Phase 1/2 Duravelo-1 study involving heavily pre-treated patients, BT8009 showed:

A promising response profile with a 38% objective response rate (ORR) in 26 patients with metastatic urothelial cancer (mUC) receiving 5 mg/m2 weekly and who had not been treated with enfortumab vedotin (EV-naïve), and a median duration of response (mDOR) of 11.1 months in 10 patients with 5 responders still on therapy. This includes 1 complete response, 7 partial responses and 2 unconfirmed responses.

Encouraging initial data in other cancers such as ovarian, triple-negative breast (TNBC) and non-small cell lung (NSCLC) that support further expansion beyond mUC.

An emerging differentiated safety profile seen in 113 patients with various types of cancer receiving 5 mg/m2 weekly, with treatment-related adverse events being primarily low in frequency and severity.

Adverse events of interest such as ocular disorders, peripheral neuropathy and skin reactions were low in frequency and severity. Importantly, treatment-related peripheral neuropathy was low-grade and often reversible, including zero cases of severe (≥Grade 3) peripheral sensory neuropathy (damage to the nerves that carry sensations like pain to the brain).

In 34 EV-naïve mUC patients, treatment-related adverse events and adverse events of interest were also low, similar to the 5 mg/m2 weekly total safety study population. Notably, there were zero cases of severe (≥Grade 3) ocular disorders, peripheral neuropathy or skin reactions.

In 7 heavily pre-treated mUC patients receiving BT8009 5 mg/m2 weekly in combination with pembrolizumab, an acceptable tolerability profile was observed with limited severe treatment-related adverse events, including zero cases of severe (≥Grade 3) ocular disorders, peripheral neuropathy or skin reactions.

Bicycle Therapeutics plans to initiate the Phase 2/3 Duravelo-2 registrational trial of BT8009 in patients with mUC in 1Q 2024 and intends to complete the Phase 1/2 Duravelo-1 open-label study across multiple cancers.

BT7480 is a Nectin-4 targeted CD137 agonist designed to overcome immune agonist toxicities and activate the immune system in Nectin-4 expressing tumors. Clinical development has been guided by safety considerations observed with first-generation CD137 agonists, the novelty of the Bicycle platform technology and the U.S. Food and Drug Administration’s (FDA) Project Optimus initiative. In a Phase 1 clinical trial, BT7480 showed:

In 33 patients assigned to receive one of 9 different doses of BT7480, an emerging differentiated safety and tolerability profile with a low number of severe adverse events. The majority of the patients studied had tumors that expressed Nectin-4 and CD137.
Two unconfirmed partial responses in heavily pre-treated patients with cervical cancer.
Three prolonged stable disease (≥7 months) in NSCLC and anal cancer.
Bicycle Therapeutics will continue to define the recommended Phase 2 dose (or maximum dose) and dose range for BT7480, with a view to enroll combination cohorts with checkpoint inhibitors in 2024. These data will inform the design of a Phase 2 trial that could support potential accelerated approval of BT7480.

Ephrin-A2 (EphA2) Portfolio

Bicycle Therapeutics is advancing one clinical program, BT5528, and one preclinical program, BT7455, targeting EphA2, a tumor antigen that is widely expressed in many cancers and has historically been difficult to target. BT7455 is an EphA2-targeted CD137 agonist whose Investigational New Drug-enabling work is ongoing.

BT5528 is an EphA2 BTC designed to overcome the significant toxicity associated with other toxin conjugate approaches that have been unsuccessful. In an ongoing Phase 1/2 clinical trial enrolling patients with various solid tumors, BT5528 showed:

In 109 patients, an acceptable emerging tolerability profile with few severe adverse events. This was also seen in 74 patients receiving 6.5 mg/m2 every other week, the dose being studied in various tumors in the expansion cohorts. Importantly, unlike other EphA2-targeted agents, no bleeding events were observed in patients treated with BT5528 at any dose.
Encouraging early activity in mUC with a 39% ORR in 18 patients receiving 6.5 mg/m2, 8.5 mg/m2 or 10 mg/m2 every other week, and an mDOR of 4 months in 7 patients with one responder still on therapy. This includes 6 partial responses and 1 unconfirmed response.
Encouraging emerging data in other cancers such as ovarian, gastric/upper gastrointestinal and head and neck that are informing the dose optimization strategy and further development.
Given the promising tolerability profile of BT5528 at 6.5 mg/m2 every other week and in line with the FDA’s Project Optimus initiative, Bicycle Therapeutics has now commenced further cohorts in mUC and ovarian cancer to test 5 mg/m2 weekly, which will inform decisions about dose optimization, potential drug combinations and expansion into other tumor types. Data from these cohorts are expected to be available in the second half of 2024.

Platform Opportunities

The company will highlight its progress in developing its next generation of Bicycle conjugates, including:

Next generation BTCs: Focusing on designing linkers specifically for BTCs, which may provide enhanced payload release into the tumor. The company plans to select a BTC clinical candidate using next-generation technology in the second half of 2024.

Bicycle Radio Conjugates (BRC): Developing a pipeline of novel binders with optimized properties for radioisotope delivery. For example, preclinical studies of a BRC targeting MT1-MMP, a high-value target in cancer treatment, showed potent anti-tumor activity and a favorable tolerability profile. Over 2024, Bicycle Therapeutics intends to generate early human imaging data from its wholly owned BRC pipeline.
Beyond Oncology: Successfully exploring other therapeutic applications of the Bicycle platform technology using non-dilutive funding, demonstrating the platform’s plug-and-play approach to precision targeting. For example, through partnerships with Dementia Discovery Fund and Ionis Therapeutics, the company demonstrated that delivery of therapies to the central nervous system, including across the blood brain barrier, can be achieved with Bicycle molecules. Bicycle Therapeutics will continue to develop Bicycle molecules to address disease outside of oncology through innovative partnerships.