On June 3, 2024 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, reported two oral presentations highlighting promising clinical data from its RP1 and RP2 programs at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31-June 4 in Chicago (Press release, Replimune, JUN 3, 2024, View Source [SID1234644023]).

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"The strength of the RP1 and RP2 data being presented at ASCO (Free ASCO Whitepaper) in two hard-to-treat tumor types further validates the potential of the RPx platform," said Sushil Patel, Ph.D., CEO of Replimune. "In the IGNYTE trial, the investigator-assessed 12-month results show an overall response rate of 32.7% that was highly durable, and the combination provided a favorable safety profile, all consistent with previous data. The data with RP2 as monotherapy and in combination with nivolumab in refractory patients highlights a strong and durable overall response rate of nearly 30 percent in uveal melanoma where treatment options are limited."

Key findings are outlined below.

Oral Presentation: Efficacy and Safety of RP1 Combined with Nivolumab in Patients with anti-PD-1-Failed Melanoma from the IGNYTE Clinical Trial (Session: Melanoma/Skin Cancers; June 3, 2024, 10:57AM CDT; Location: S406; Abstract: 9517)

The data continues to show that the combination of RP1 and nivolumab in anti-PD-1 failed melanoma (n=156) provides deep and durable responses with an "on-target" safety profile with generally transient grade 1/2 adverse events, indicative of systemic immune activation.
Approximately one third of patients experienced a response, with an overall response rate (ORR) by investigator assessment of 32.7%.
In the 94 patients who had primary resistance to their immediate prior anti-PD-1 therapy, the ORR was 34%.
In the 66 patients who progressed on prior anti-PD-1 combined with anti-CTLA-4 therapy, the ORR was 27.3%.
All responses lasted greater than six months from enrollment, with a median duration of response exceeding 36 months.
Clinically meaningful activity was observed across all enrolled subgroups, with over half of patients experiencing either a complete response (CR), partial response (PR) or stable disease (SD).
Primary analysis results by independent central review from the IGNYTE anti-PD-1 failed melanoma cohort are expected later in Q2 2024 with the Company on track to submit a biologics license application (BLA) for RP1 to the U.S. Food and Drug Administration (FDA) in 2H 2024. The Company also has agreed on a protocol for a Phase 3 confirmatory study with the FDA (IGNYTE-3; NCT06264180; poster TPS9603, ASCO (Free ASCO Whitepaper) 2024) and expects to initiate the trial prior to the RP1 BLA in anti-PD-1 failed melanoma being submitted.

"The findings shared for the IGNYTE clinical trial underscore the promising effects of RP1 shown to date, including overall response rate, durability and safety," said Michael Wong, M.D., Ph.D., Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and presenter of the study. "RP1 plus nivolumab provides an attractive risk-benefit profile for melanoma patients who have progressed on PD1 based treatment, particularly when compared with other therapies. For this population – the unmet need is significant as there are limited options with only about half of patients with melanoma responding to first line treatment."

Oral Presentation: Safety, Efficacy, and Biomarker Results from an Open-Label, Multicenter, Phase 1 Study of RP2 Alone or Combined with Nivolumab in a Cohort of Patients with Uveal Melanoma (Session: Melanoma/Skin Cancers, June 3, 2024, 9:57AM CDT; Location: S406; Abstract: 9511)

The data suggest that RP2, which expresses an anti-CTLA-4 antibody, dosed both alone and in combination with an anti-PD-1 agent in metastatic uveal melanoma patients (n=17), including those with both liver and extra-hepatic metastases, had a favorable safety profile and durable anti-tumor activity.
RP2 administered as monotherapy or in combination with nivolumab demonstrated an ORR of 29.4%, with a disease control rate (DCR) of 58.8%.
Biomarker data indicate immune cell infiltration and increased PD-L1 expression in tumors, together with changes in the systemic T cell repertoire following RP2 plus nivolumab.
Based on the encouraging ORR observed amongst a patient population with historically poor treatment outcomes, Replimune is currently finalizing the protocol for a registration-directed study based on FDA input.
Both presentations will be available on the Company website under Events and Presentations.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.

About RP2
RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

On June 3, 2024 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported the issue of a new Chinese patent notice of allowance for opaganib4 in combination with immune checkpoint inhibitors (ICIs) as a method of inducing an anti-cancer immune response, providing protection for opaganib’s potential use with a range of approved and in-development immune checkpoint inhibitors (ICIs) across a growing range of indications through 2040 (Press release, RedHill Biopharma, JUN 3, 2024, View Source [SID1234644022]). The patent will be issued by the Chinese National Intellectual Property Administration (CNIPA) (Chinese Patent Application No.: 202080013805.3 issued May 24, 2024).

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"ICIs have become a cornerstone in cancer treatment, having been hailed as a major breakthrough by oncologists, with the global ICI market expected to exceed $100 billion by 2028, including Merck’s Keytruda (pembrolizumab) and BMS’ Yervoy (ipilimumab)," said Guy Goldberg, RedHill’s Chief Business Officer. "This exciting new patent is based on compelling data from a range of in vivo experiments showing significant improvements in outcomes in combination with selected ICIs. China has been a world leader in embracing ICI-based therapy5 and this is an important addition to the strong patent portfolio protecting opaganib."

About Opaganib (ABC294640)
Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including prostate cancer and cholangiocarcinoma (bile duct cancer), gastrointestinal acute radiation syndrome (GI-ARS), Sulfur Mustard exposure, COVID-19, Ebola and other viruses as part of pandemic preparedness.

Opaganib’s host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

Opaganib has been selected for evaluation by two U.S. government countermeasures programs for Acute Radiation Syndrome (ARS) and Sulfur Mustard exposure, both funded by the NIH: The Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the HHS National Institutes of Health, for the nuclear medical countermeasures (MCM) product development pipeline selected opaganib for development as a potential treatment for Acute Radiation Syndrome (ARS); and the Chemical Medical Countermeasures (Chem MCM) Program and Chemical Countermeasures Research Program (CCRP), managed respectively by the Administration for Strategic Preparedness and Response (ASPR) / Biomedical Advanced Research and Development Authority (BARDA) and NIH/NIAID selected opaganib for evaluation as a potential medical countermeasure (MCM) against Sulfur Mustard exposure.

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury, Gilead Sciences Inc.), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study.

Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv.

Opaganib has received Orphan Drug designation from the FDA for the treatment of cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.

Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications.

On June 3, 2024 NKGen Biotech, Inc. (Nasdaq: NKGN) ("NKGen" or the "Company"), a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic and CAR-NK natural killer ("NK") cell therapeutics, reported that Paul Y. Song, MD, Chairman and Chief Executive Officer of NKGen Biotech, will present details on their cryopreserved allogeneic NK cell therapy platform as well as updated Phase 1 data on its use in solid tumors without lymphodepletion at the 6th Annual Allogeneic Cell Therapies Summit to be held in Boston, MA, from June 10-12, 2024 (Press release, NKGEN Biotech, JUN 3, 2024, View Sourcenkgen-biotech-to-present-updated-phase-1-data-on-snk02-allogeneic-nk-cell-therapy-in-solid-tumors-at-the-6th-annual-allogeneic-cell-therapies-summit-2024/" target="_blank" title="View Sourcenkgen-biotech-to-present-updated-phase-1-data-on-snk02-allogeneic-nk-cell-therapy-in-solid-tumors-at-the-6th-annual-allogeneic-cell-therapies-summit-2024/" rel="nofollow">View Source [SID1234644021]).

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Presentation Details:

Title: Protecting Patients by Removing Need for Lymphodepletion to Better Preserve Immune Function

Conference Track: Clinical Track

Date and Time: Wednesday, June 12, 2024, 12:00 pm ET

Dr. Song’s presentation will detail the Company’s novel allogeneic blood-derived NK cell therapy ("SNK02") commercial manufacturing and cryopreservation process, as well provide an update on their initial Phase 1 results using SNK02 to treat patients with advanced refractory solid tumors. Furthermore, Dr. Song will explore the potential benefits of eliminating pre-treatment lymphodepletion in patients undergoing SNK02 therapy, aiming to safeguard immune function and aid in recovery. Avoiding lymphodepletion before administering cancer treatment can provide many benefits including reduced toxicity, preservation of immune function, and potentially enhancing treatment efficacy. The presentation will also include a discussion on an unexpected discovery from the SNK02 Phase 1 trial, hinting at its possible applicability as a treatment for patients beyond cancer.

A copy of the presentation will be available on the Scientific Publications page of the Company’s website at View Source once the presentation has concluded. Previously disclosed Phase 1 data on the positive effects of SNK02 on advanced solid tumors, which may not be included in this conference presentation, can also be found on the Scientific Publications page.

About SNK02

SNK02 is a novel cell-based, donor-derived ex vivo expanded allogeneic NK cell immunotherapeutic drug candidate. NKGen Biotech, Inc. is developing SNK02 for the treatment of a broad range of cancers.

On June 3, 2024 Mythic Therapeutics, a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported initial dose escalation results from its ongoing Phase 1 KisMET-01 study evaluating its investigational cMET-targeting ADC, MYTX-011, in patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, JUN 3, 2024, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-initial-dose-escalation-data-from-ongoing-phase-1-kismet-01-study-on-mytx-011-at-the-american-society-of-clinical-oncology-asco-annual-meeting [SID1234644019]).

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"The initial dose escalation results from our ongoing Phase 1 KisMET-01 study, coupled with the previously presented preclinical data are encouraging and underscore MYTX-011’s potential to serve patients with a broad range of cMET expression," said Gilles Gallant, BPharm, Ph.D., FOPQ, Chief Development Officer at Mythic Therapeutics. "ADCs have been a transformative class of treatment for patients impacted by cancer, but we know that there is a large population of patients with low-to-moderate target expression who are unlikely to benefit from them. These initial data potentially represent significant promise for patients who have historically been ineligible for treatment due to their level of target expression or tumor type, and we look forward to continuing our dose escalation and expansion study."

MYTX-011 is a novel cMET-targeted DAR 2 vcMMAE ADC with an antibody that has been engineered to have pH-dependent binding, which results in higher internalization and payload delivery to tumor cells with a range of cMET expression.

KisMET-01 (NCT05652868) is a multicenter, first-in-human study of MYTX-011 in patients with previously treated, locally advanced or metastatic NSCLC. The study is comprised of a Part 1 dose escalation in patients with NSCLC of any histology and regardless of cMET expression level, followed by Part 2 dose expansion in cohorts specified by cMET expression and histology. The primary objectives of Part 1 are to assess safety and tolerability and determine the recommended phase 2 dose. Secondary objectives include assessment of pharmacokinetics (PK) and preliminary anti-tumor activity.

As of April 30, 2024, 42 patients had been enrolled and received at least one dose of MYTX-011. Data from 41 patients was available by data cutoff and median follow-up was 15 weeks. Patients were dosed between 1.0 to 6.7 mg/kg on a once every three weeks schedule (Q3W). Treated patients had a median of three prior lines of therapy. As of data cutoff, PK data were available in patients who received doses 1.0 to 5.0 mg/kg. PK of MYTX-011 showed nearly dose proportional exposure up to 5.0 mg/kg. Little separation of ADC and total mAb concentration was noted, suggesting good stability of MYTX-011, supporting dosing every 3 weeks. MYTX-011 has been well tolerated with low incidence of common AEs associated with MMAE or cMET targeted therapeutics. No dose-limiting toxicity was reported, and dose escalation is ongoing. Given that dose escalation is ongoing and the overall median follow-up as of the data cutoff was 15 weeks, efficacy data will be presented in a future conference or publication.

"Patients with locally advanced or metastatic NSCLC who have not responded or become resistant to previous therapies represent an urgent unmet need," said Melissa Johnson, M.D., Director of Lung Cancer Research at Sarah Cannon Research Institute. "Observing the favorable safety, tolerability and PK of MYTX-011 across a diverse range of cMET-expressing patients is encouraging. We look forward to seeing additional safety and efficacy data from the Phase 1 study."

About MYTX-011

MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl technology which is designed to allow ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

On June 3, 2024 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage company focused on the discovery and development of targeted biologic therapeutics with unique mechanisms of action (engineered toxin bodies or "ETBs") for cancer and immune-mediated disease, reported an update on its clinical-stage programs (Press release, Molecular Templates, JUN 3, 2024, View Source [SID1234644018]).

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Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, "ETBs are a potentially powerful therapeutic approach to selectively depleting immunosuppressive cells in oncology or eliminating self-reacting immune cells in severe immune-mediated diseases. The monotherapy activity we see with MT-6402 in relapsed/refractory solid tumor patients, and the clinical and ex vivo depletion of CD38+ immune cells seen with MT-0169 at well-tolerated doses underscore the potential of this platform across multiple diseases."

Company Pipeline Highlights

MT-6402 (PD-L1-targeting ETB)

Promising Single-Agent Activity: MT-6402 has shown monotherapy activity in heavily pre-treated patients who had previously progressed or were refractory to immuno-oncology therapy.
Head and Neck Cancer Responses: MTEM had previously reported that nine patients (seven evaluable) with head and neck squamous cell carcinoma ("HNSCC") had been treated in the Phase 1 dose escalation. Two heavily pre-treated patients with low PD-L1 expressing squamous cell carcinoma of the head and neck (HNSCC) had achieved partial responses with MT-6402 monotherapy. These patients remain in response and in good clinical condition, continuing treatment in cycles 21 and 12 (one cycle = 4 weeks), respectively. In addition, four of the HNSCC patients treated with MT-6402 had stable disease with two showing tumor reduction. All patients with tumor responses or tumor reduction had low PD-L1 expression (≤20% CPS).
New Lung Cancer Response: An unconfirmed partial response was observed in a non-small cell lung cancer ("NSCLC") patient with high PD-L1 expression in the Phase 1b monotherapy dose expansion study in solid tumor patients with high PD-L1 tumor expression (TPS≥50%). The patient achieved a partial response at the end of cycle 8 following sustained tumor reduction in prior assessments. A PET scan in cycle 8 showed no indications of active metastatic disease. This patient had previously progressed on chemotherapy, targeted therapy, and checkpoint therapy, including progression within six months on pembrolizumab + ramucirumab, before enrolling in the study. Three other NSCLC patients with high PD-L1 expression have been dosed in the Phase 1b expansion study. Two of these patients had progressive disease and one passed away from COVID and was not evaluable.
Favorable Safety Profile: To date, MT-6402 appears to be generally well-tolerated, with no drug-related adverse events exceeding grade 3.
Ongoing Enrollment: MTEM continues to enroll HNSCC patients with low PD-L1 expression (1-49%) and patients with solid tumors with high PD-L1 expression (≥50%).
MT-0169 (CD38-targeting ETB)

Clinical proof-of-concept supports the elimination of CD38+ cells in immune-mediated disease. Recent clinical data with CD38 antibodies have demonstrated the therapeutic potential of CD38+ immune cell clearance in several immune-mediated diseases. Despite these promising early data, a more potent mechanism of CD38+ immune cell depletion may provide greater clinical benefit.
Potent and unique mechanism of action. MT-0169 is designed to destroy CD38+ tumor or immune cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and ER stress). In ex vivo cell kill assays, MT-0169 shows potency against plasma cells with IC50 activity in the picomolar or femtomolar range. Plasma cells are exceptionally sensitive to ER stress, making them uniquely susceptible to the MT-0169 mechanism of action. MT-0169 also shows potent activity against T-cells that express low levels of CD38. HLA-DR CD38+ T-cells have been implicated in many immune-mediated diseases.
Overcoming antibody resistance. The unique mechanism of action of MT-0169 and its lack of an Fc domain may avoid resistance mechanisms seen with CD38 antibodies like receptor downregulation or trogocytosis while allowing for combination approaches with FcRn-targeting therapies.
Clinical proof-of-concept with MT-0169. MTEM’s Phase 1 study in patients with relapsed or refractory multiple myeloma dosed at 5, 10, or 15 mcg/kg showed potent depletion of CD38+ immune cells with no drug-related adverse events of grade 3 or higher noted in these patients.
Planned clinical development with MT-0169. MTEM will continue to develop MT-0169 in hematology and is evaluating the potential of MT-0169 in severe immune-mediated diseases.
MT-8421 (CTLA-4 ETB)

Tumor microenvironment dismantling. MT-8421 is designed to potently destroy CTLA4+ Tregs, alleviating immunosuppression in the tumor microenvironment.
Pharmacodynamic effects observed early Phase 1 dose escalation. Three patients were dosed in the first cohort of the Phase 1 study at 32 mcg/kg. No drug-related adverse events of grade 3 or higher were observed. One patient had disease progression at the end of cycle 2. Two patients have stable disease and remain on study at cycle 8 and cycle 7, respectively (one cycle = four weeks). The two patients in stable disease showed peripheral depletion of Tregs and significant elevations in IL-2 while on therapy. One of the patients has a notable decrease in ctDNA.
Dose escalation continues. Enrollment is on-going in the second cohort of 48 mcg/kg for the Phase 1 study of MT-8421.