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NeoImmuneTech and Imugene enter into strategic research collaboration to improve cancer treatments

On December 12, 2023 Imugene Ltd ("Imugene") (ASX: IMU), a clinical stage immuno-oncology company, and NeoImmuneTech, Inc. ("NIT"), (KOSDAQ: 950220) a clinical-stage T-cell-focused biopharmaceutical company, reported a strategic collaboration to evaluate Imugene’s allogeneic CAR T, azer-cel, in combination with NIT’s proprietary immune T cell amplifier "Fc-fused recombinant human interleukin-7", NT-I7, for the treatment of cancer (Press release, NeoImmuneTech, DEC 12, 2023, https://mcusercontent.com/e38c43331936a9627acb6427c/files/6a6df5ec-bcfd-bb50-bb42-3b1d0e5e3600/Imugene_and_NeoImmuneTech_to_Improve_Cancer_Treatments.pdf [SID1234638448]).

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Azer-cel is an allogeneic CD19 CAR T cell therapy program with extensive clinical data and a potentially fast-to-market development strategy. Azer-cel has demonstrated clinically meaningful activity with an acceptable safety profile in blood cancers such as lymphoma and leukemia.

NT-I7 (efineptakin alfa) is the only long-acting human IL-7 cytokine in clinical stage development. NT-I7 plays a key role in T cell development and survival, boosts cancer fighting T cell numbers, their health, and functionality to enhance immune function and potentially provides improved cancer fighting benefits to patients. NT-I7 exhibits favorable stability, activity and safety profiles on patient dosing compared with naturally occurring IL-7, making it an ideal combination partner for cell therapy drugs like azer-cel.

"We are delighted to be working with NIT on the potential to enhance azer-cel activity as part of this research collaboration," said Leslie Chong, Managing Director & Chief Executive Officer of Imugene.

Dr. Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech said: "NT-I7 has already shown encouraging results in multiple indications in immuno-oncology and infectious diseases, both as a monotherapy or in combination. The research collaboration with Imugene, an industry leader in allogeneic cell therapy, could greatly expand the potential of our asset and accelerate its path to commercialization, as we did in acute radiation syndrome."

The strategic collaboration is effective immediately and will continue for two years whilst there are relevant research activities being performed under the research plan. Such research activities will be performed exclusively in the United States. The strategic collaboration may be terminated upon completion of the research activities, by agreement, or according to common commercial termination provisions. Imugene will fund its component of the strategic collaboration by its existing planned research activities. No additional or new funding is required for the initial activities by Imugene for the strategic collaboration. The funding of Imugene research activities is material and is allowed for in the Company’s existing research budget.

Each party has full intellectual property (IP) rights (patents) to their individual background technology. In the event new IP is generated from the strategic collaboration (each a "Joint Collaboration Technology"), the parties shall discuss in good faith the filing, prosecution, maintenance, enforcement, defense of any patent applications relating thereto, as well as each party’s right to use, such Joint Collaboration Technology.

Alphamab’s Novel Subcutaneous Anti-HER2 Bispecific ADC JSKN033 Approved for Clinical Studies in Australia

On December 11, 2023 Alphamab Oncology (stock code: 9966.HK) reported that the independently developed global first subcutaneous injection HER2 bispecific antibody-conjugated drug (JSKN033) has received approval from the Australian Bellberry Clinical Research Ethics Committee to conduct clinical studies (JSKN033-101) for the treatment of HER2-expressing advanced or metastatic solid tumors.

JSKN033-101 is an open-label, muticenter, phase I/II clinical study. The study consists of dose escalation and dose expansion phases: The Phase I dose escalation stage aims to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of JSKN033 in patients with advanced or metastatic HER2-expressing solid tumors, determining the maximum tolerated dose (MTD) and/or Phase II recommended dose (RP2D); the Phase II dose expansion stage will evaluate the efficacy and safety of JSKN033 in HER2-expressing gastrointestinal tumors at the RP2D dose.

JSKN033 is a subcutaneous injection compound consisting of JSKN003 and envafolimab, independently developed by Alphamab. JSKN033 is expected to provide effective innovative therapy for patients and doctors through IO and ADC combo and have better safety profile and convenience due to the nature of SubC injectables.

About JSKN033

JSKN033 is the global first subcutaneous injection HER2 bispecific antibody-conjugated drug developed by Alphamab, which is composed of JSKN003 and envafolimab. JSKN003 is a HER2 dual-epitope-targeting antibody-conjugated drug composed of three parts: bispecific antibodies targeting two non-overlapping epitopes of the HER2 extracellular domain, a cleavable linker, and a topoisomerase I inhibitor. Envafolimab is a Fc fusion protein consisting of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment, which has been approved by China NMPA as the global first subcutaneously administered PD-L1 inhibitor and marketed in China.

(Press release, Alphamab, DEC 11, 2023, View Source [SID1234657029])

Genor Biopharma presents the safety and efficacy results of GB261 at 2023 ASH

On December 11, 2023 Genor Biopharma (Stock code: 6998.HK) reported the company participated at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held in San Diego, USA on December 9-12, 2023, and shared the poster of the preliminary clinical safety and efficacy results of the phase I/II study of GB261(CD20/CD3) (Press release, Genor Biopharma, DEC 11, 2023, View Source [SID1234656303]).

GB261, an Fc-Function Enabled and CD3 Affinity De-Tuned CD20/CD3 Bispecifc Antibody, Demonstrated a Highly Advantageous Safety/Efficacy Balance in an Ongoing First-in-Human Dose-Escalation Study in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma (Poster Number: 1719)

Introduction:
GB261 is a novel and highly differentiated CD20/CD3 bispecific T cell engager antibody computationally designed to maintain Fc effector function, i.e., antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) to broaden the mechanisms of action (MOA) for tumor cell killing. Furthermore, the "imbalanced" design of GB261 integrates de-tuned CD3 binding to reduce CRS incidence and improve safety features of the Fc effector function. Extensive pre-clinical studies have shown that GB261 has a highly advantageous safety/efficacy balance. Here, we present the preliminary clinical safety and efficacy results of an ongoing phase I/II study for GB261 (NCT04923048).

Methods:
This is an open-label, multicenter (China and Australia), dose escalation/expansion phase 1/2 study of GB261 to evaluate the safety, tolerability and efficacy in patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma(B-NHL) and Chronic Lymphocytic Leukemia (CLL). Adult patients were eligible when they have CD20+ r/r B-NHL or CLL with no available standard of care treatments, adequate organ function, and no CNS involvement or other CNS disease, infections or other active/serious medical issues that may affect compliance or interpretation of results. GB261 was administered in 21-day cycles, weekly (QW) for the first 6 doses followed by every 3 weeks (Q3W) until disease progression, or other situation defined in protocol. Response assessment was based on Lugano 2014 and LYRIC 2016 criteria.

Results:
As of June 17, 2023, 47 r/r B-NHL patients (DLBCL:76.6%; FL:23.4%) were enrolled at flat or step-up doses of GB261 ranging from 1mg to 300mg. Median age was 60.0 years (range: 28, 81), 55.3% of patients were male. Median prior lines of therapy were 3 (range: 1, 10). 78.7% of patients were refractory to any anti-CD20 therapy, 70.2% refractory to their last systemic therapy. Median time since last prior therapy to first study treatment was 1.9 months.

In efficacy evaluable patients (n=22) from 3mg to 100mg, with at least 75% dose exposure before the first radiographic assessment, the median duration of study follow-up was 4.5 months (95%CI: 4.0, 7.4). The overall response rate (ORR) was 73% (16/22), and complete response rate (CRR) was 45.5% (10/22). ORR and CRR were 100% and 100% in 3mg, 56% and 22% in 10mg, 67% and 33% in 30mg. At 100mg dose, there were 5 evaluable patients, with ORR 100% (5/5), CRR 80% (4/5) and PR (20%, 1/5; mosunetuzumab-refractory rrDLBCL patient). Median time to response (TTR) was 1.3 months (95%CI: 1.2, 1.5), the same as median time to CR. Median duration of response (DOR) was not reached.

In safety evaluable patients (n=47), the median duration of study follow-up was 4.1 months (95%CI: 2.9, 5.3). Treatment-emergent adverse events (TEAEs) were 95.7%, treatment-related adverse events were 85.1%. The most common TEAEs were COVID-19 infection (40.4%; grade 1 or 2: 27.6%; grade >=3: 12.8%) and neutropenia (31.9%; grade 1or 2: 14.9%; grade >=3: 17.0%). AE related treatment discontinuation and death were reported in 2 patients, which were all due to COVID-19 pneumonia. CRS occurred in 12.8% (6/47) patients, was mild and transient. CRS in 100mg were 14.3% (2/14). All cases of CRS were grade 1 (8.5%, 4/47) or 2 (4.3%, 2/47), no grade 3 (Lee et al., ASTCT criteria), no interruptions of treatment, and no administration of Tocilizumab. The median duration of CRS was 7 hours. No ICANS were reported.

The PK profile of GB261 appeared to be linear across dose ranges tested (1mg -100mg). Effective half-life appeared to be 2-3 weeks which supports every 3-4 weeks dosing.

Conclusion:
GB261, a novel and highly differentiated CD20/CD3 bispecific antibody, is the first clinical stage Fc+ CD20/CD3 T cell engager. In heavily pretreated B-NHL patients, GB261 showed a highly advantageous safety/efficacy balance, consistent with the MOA. The safety profile is excellent especially for the CRS which is very mild, transient and less frequent compare with other CD20/CD3 bispecific antibodies. The response after GB261 treatment was early, deep and durable. At the 100mg dose level, 80% of patients achieved CR and with favorable safety. Additionally, clinical benefit seen in other CD20/CD3 bispecific antibody failed patients provides clinical support to the unique and differentiated MOA of GB261.

Erasca Granted FDA Fast Track Designation for Pan-RAF Inhibitor Naporafenib in Patients with Advanced NRAS-Mutated Melanoma

On December 11, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to naporafenib in combination with trametinib (MEKINIST) for the treatment of adult patients with unresectable or metastatic melanoma who have progressed on, or are intolerant to, an anti‑programmed death-1 (ligand 1) (PD‑(L)1)-based regimen, and whose tumors contain an NRAS mutation (NRASm) (Press release, Erasca, DEC 11, 2023, View Source [SID1234639350]). Naporafenib is an orally available, Phase 3-ready pan-RAF inhibitor with a potential first-in-class and best-in-class profile in NRASm melanoma and other RAS/MAPK pathway-altered solid tumors.

FTD is designed to help drugs reach patients faster by facilitating the development and expediting the review of drugs with the potential to fill an unmet medical need by treating a serious or life-threatening condition. Programs that receive FTD benefit from early and frequent interactions with the FDA during the clinical development process and, if relevant criteria are met, the FDA may consider reviewing portions of a marketing application before the sponsor submits the complete application.

"The outcomes for patients with NRASm melanoma after frontline immunotherapy (IO) treatment are dismal with low response rates and short median progression free survival (mPFS). By contrast, as previously presented by Novartis at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 and as published in March 2023 by de Braud et al. in the Journal of Clinical Oncology, naporafenib in combination with trametinib has demonstrated strong and durable anti-tumor activity," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "We are now rapidly advancing clinical development of naporafenib in combination with trametinib in the post-IO setting in patients with NRASm melanoma with initiation of our pivotal Phase 3 SEACRAFT-2 trial expected in the first half of 2024. Receiving FTD further strengthens our ability to work closely with the FDA toward our goal of bringing this new therapy for difficult-to-treat melanoma to patients as soon as possible."

NRASm melanoma comprises 20-30% of all melanomas and is associated with a worse prognosis compared to other alterations. Effective treatment options are needed for patients following progression on frontline IO with anti-CTLA-4 and/or anti-PD-(L)1 antibodies. Currently, chemotherapy is the approved post-IO standard of care with a 7% objective response rate (ORR) and 1.5 months mPFS (historical Phase 3 data generated when the drug was administered in the front-line/second-line setting). While not approved in this indication in the United States, the MEK inhibitor binimetinib is used off label and demonstrated a 15% ORR and 2.8 months mPFS (historical Phase 3 data generated when the drug was administered in the front-line/second-line setting). There are currently no approved therapies that target NRAS mutations. Erasca recently reported that End of Phase 2 meetings with the FDA and European health authorities confirmed the SEACRAFT-2 Phase 3 trial design and provided clarity on the registrational pathway.

About SEACRAFT-2
SEACRAFT-2 is a randomized, pivotal Phase 3 trial that will evaluate the clinical efficacy of naporafenib in combination with trametinib (MEKINIST) compared to physician’s choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in the post-immunotherapy setting in patients with NRAS-mutated metastatic melanoma. Initiation of the SEACRAFT-2 trial is expected in H1 2024.

About Naporafenib
Naporafenib (formerly LXH254) is a potent and selective pan-RAF inhibitor, with a potential first-in-class and best-in-class profile. Naporafenib has been dosed in over 500 patients to date, whereby safety, tolerability, pharmacokinetics, and pharmacodynamics have been established in both monotherapy and select combinations. Clinical proof-of-concept (PoC) has been established for the combination with trametinib for patients with NRAS-mutant (NRASm) melanoma, which includes NRAS Q61X melanoma, and preliminary clinical PoC has been established for the combination with trametinib for patients with RAS Q61X in non-small cell lung cancer (NSCLC). Erasca plans to focus initially on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the planned pivotal Phase 3 SEACRAFT-2 trial and in RAS Q61X tissue agnostic solid tumors as part of the Phase 1b SEACRAFT-1 trial, respectively. Erasca is also exploring additional combinations of naporafenib with other proprietary therapeutic agents in our pipeline. Naporafenib has received FDA Fast Track Designation for patients with advanced NRASm melanoma.

Kirilys Therapeutics to Present Preclinical Profile for KRLS-017, a reversible inhibitor of CDK7 for Oncology

On December 11, 2023 Kirilys Therapeutics, Inc., a multi-asset biotechnology company founded by investment firm Catalys Pacific and supported by Lightspeed Venture Partners, reported to present a detailed preclinical profile for KRLS-017 at AACR (Free AACR Whitepaper) 2024 in San Diego, CA (Press release, Kirilys Therapeutics, DEC 11, 2023, View Source [SID1234638566]).

KRLS-017 is a potent, selective, and reversible inhibitor of Cyclin Dependent Kinase 7 (CDK7) and is being developed for the treatment of patients with advanced solid tumor malignancies. CDK7 function in control of both cell cycle and gene transcription, and overexpression of CDK7 is a poor prognostic indicator in breast, ovarian, gastric, and other tumor types.

The preclinical presentation titled "Preclinical evaluation of KRLS-017, a potent, highly selective and reversible CDK7 inhibitor with broad antitumor effect in preclinical models, in preparation for a Phase 1 clinical trial in advanced solid tumor malignancies" will include pharmacology, toxicology, and efficacy across several dosing schedules using in vivo tumor models. A Phase 1 clinical program for KRLS-017 is planned as a monotherapy dose escalation study in refractory solid tumors followed by an indication-specific cohort expansion that will include breast, ovarian and potentially other transcriptionally active tumor types to evaluate anti-tumor activity.